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Objective The main aim of this study was to ascertain the effectiveness of ultrasound-guided fine needle aspiration cytology (US-FNAC) in the diagnosis of para-aortic lymph node (PALN) metastasis in uterine cervical cancer and to establish its potential impact on clinical therapeutic decision making. Methods We retrospectively reviewed clinical data from 92 patients diagnosed with cervical cancer with PALN enlargement between 2010 and 2018. Cytological results obtained with US-FNAC were classified by the same experienced cellular pathologists. Diagnostic indicators were determined on the basis of biopsy, imaging and clinical follow-up results. Univariate and multivariate analyses were used to assess the differences of influencing factors. The effect of US-FNAC on clinical decision making was evaluated. Results Cytological results of US-FNAC were categorized as malignancy (n = 62; 67.4%), suspicious malignancy (n = 11; 12.0%), undetermined (n = 5; 5.4%), benign (n = 10; 10.9%), and inadequate (n = 4; 4.3%). Satisfactory biopsy samples were obtained from 95.7% of PALNs sampled (88/92). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC in distinguishing benign from malignant cases were 90.1% (95% CI: 0.809–0.953), 100% (95% CI: 0.561–1), 100% (95% CI: 0.938–1), 46.7% (95% CI: 0.223–0.726) and 90.9% (95% CI: 0.848–0.970), respectively. Univariate analysis indicated significant differences in experience of puncture physicians (radiologists) between the correct and wrong diagnosis groups (P p = 0.031, OR = 0.077, 95% CI: 0.354–0.919). All patients tolerated the US-FNAC procedure well and only nine presented slight abdominal discomfort. The therapeutic strategies for 74 patients (80.4%) were influenced by US-FNAC findings. Conclusions US-FNAC was a relatively safe and effective technique for examination of enlarged para-aortic lymph nodes and may therefore serve as a routine diagnostic tool to guide clinical decision making for management of cervical cancer.

Aims Anti‐leucine‐rich glioma‐inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by complex manifestations of seizures. Here, we report a new seizure semiology, attempt to classify the disease by semiology type, and explore the metabolic pattern of each group. Methods Anti‐LGI1 AE patients were retrospectively screened between May 2014 and September 2019 in our tertiary epilepsy center. All enrolled patients had seizures during long‐range video electroencephalogram (EEG) recordings, and all patients (except one) underwent [18F] fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) scans. Voxel‐based metabolic analysis and z‐distribution analysis were carried out to determine the metabolic pattern. Results Thirty‐three patients were enrolled. According to the patients’ seizure semiology, we divided the patients into four groups: focal impaired awareness seizures (FIAS, n = 17), faciobrachial dystonic seizures (FBDS)‐only (n = 6), FBDS‐plus (n = 8), and focal aware motor seizures (FAMS) (n = 2). No significant differences were found in the clinical manifestations or accessory tests except for the onset age (FIAS, Dozens of clinical and subclinical seizures were detected in the long‐range video EEG recording of an anti‐LGI1 encephalitis patient with focal aware motor seizures (A). Furthermore, FDG‐PET scans showed a wide range of abnormal metabolic pattern of this patient and patients with other seizure semiologies, which is not limited to the temporal regions and basal ganglia and far beyond our previous interpretation (B).

Spinal muscular atrophy (SMA) is an autosomal recessive, fatal neurological disorder in children. The pathogenic gene of SMA is survival motor neuron1 (SMN1). There are many methods to detect SMN1 gene copy number, but few techniques are suitable for large-scale population screening. In order to find a rapid and accurate experimental technique for mass screening of SMA carriers in the population, the SMN1 gene copy number of 12 SMA patients and their parents was analyzed by multiplex competitive PCR combined with capillary electrophoresis. Meanwhile, the copy number of SMN1 gene in 151 healthy pregnant women in Jiangsu was screened with the MLPA technology to confirm their copy number of the SMN genes. The results showed that the 12 SMA patients had 0 copy of SMN1 gene, and all their parents had 1 copy of SMN1 gene only. Among 151 healthy subjects, 3 cases (2.0%) had 1 copy of SMN1 gene, and hence designated as SMA carriers. One hundred and thirty-four cases (88.7%) had 2 copies of the SMN1 gene. There were 14 cases (9.3%) with more than 2 copies of the SMN1 gene. Therefore, multiplex competitive PCR combined with capillary electrophoresis is a rapid, simple and accurate method for the detection of SMA carriers; and potentially applicable to mass screening of SMA carriers in the population.脊髓性肌萎缩症(spinal muscular atrophy, SMA)是一种常染色体隐性遗传、儿童致死性神经系统疾病。SMA致病基因为运动神经元存活基因(survival motor neuron1, SMN1)。虽然检测SMN1基因拷贝数的方法众多,但目前适于大规模人群筛查的技术较少。为寻求一种快速准确的实验技术可以用于人群中SMA携带者的大规模筛查,了解区域人群携带情况及常见变异的分布,本研究应用多重竞争性PCR联合毛细管电泳技术检测12例SMA患者及其父母SMN1基因拷贝数,同时对江苏地区151例健康孕妇人群SMN1基因进行拷贝数检测,并通过多重连接依赖探针扩增(multiplex ligation-dependent probe amplification, MLPA)技术验证检测结果。多重竞争性PCR联合毛细管电泳技术结果与MLPA结果一致,显示12例SMA患者均为SMN1基因零拷贝,其父母的SMN1基因拷贝数均为单拷贝,151例健康人群中检测出SMN1基因单拷贝3例(即SMA携带者),占2.0%;SMN1基因双拷贝134例,占88.7%;SMN1基因大于双拷贝14例,占9.3%。因此,多重竞争性PCR联合毛细管电泳技术作为一种快速、简便和准确的检测技术具有着应用于人群中SMA携带者的大规模筛查的潜力。.

Background Thyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet. Methods TC cell lines (IHH4 and TPC-1) were used. Flow cytometry was used to identify the surface marker of M2-like tumor-associated macrophages (TAMs) from cell culture. Quantitative real-time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β-catenin pathway, and proliferation/epithelial-mesenchymal transition (EMT)-related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β-catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice. Results Coculture with M2-like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation-related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β-catenin signaling pathway, and suppressed EMT and proliferation-related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model. Conclusion M2-like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β-catenin activation.

Preeclampsia (PE) is a pregnancy complication characterized by severe hypertension and multiple organ damage. Gut microbiota has been linked to PE by previous amplicon sequencing studies. To resolve the PE gut microbiota in a higher taxonomy resolution, we performed shotgun metagenomic sequencing on the fecal samples from 40 early-onset PE and 37 healthy pregnant women. We recovered 1,750 metagenome-assembled genomes (representing 406 species) from the metagenomic dataset and profiled their abundances. We found that PE gut microbiota had enriched in some species belonging to Blautia, Pauljensenia, Ruminococcus, and Collinsella and microbial functions such as the bacitracin/lantibiotics transport system, maltooligosaccharide transport system, multidrug efflux pump, and rhamnose transport system. Conversely, the gut microbiome of healthy pregnant women was enriched in species of Bacteroides and Phocaeicola and microbial functions including the porphyrin and chlorophyll metabolism, pyridoxal-P biosynthesis, riboflavin metabolism, and folate biosynthesis pathway. PE diagnostic potential of gut microbial biomarkers was developed using both species and function profile data. These results will help to explore the relationships between gut bacteria and PE and provide new insights into PE early warning.

Objective Type I sialidosis (ST‐1) is a rare autosomal recessive inherited disorder. To date, there has been no study on ST‐1 patients in mainland China. Methods We reported in detail the cases of five Chinese ST‐1 patients from two centers, and summarized all worldwide cases. Then, we compared the differences between Chinese and foreign patients. Results A total of 77 genetically confirmed ST‐1 patients were identified: 12 from mainland China, 23 from Taiwan, 10 from other Asian regions, and 32 from European and American regions. The mean age of onset was 16.0 ± 6.7 years; the most common symptoms were myoclonus seizures (96.0%), followed by ataxia (94.3%), and blurred vision (67.2%). Compared to other groups, the onset age of patients from mainland China was much younger (10.8 ± 2.7 years). The incidence of visual impairment was lower in patients from other Asian regions than in patients from mainland China and Taiwan (28.6% vs. 81.8%–100%). Cherry‐red spots were less frequent in the Taiwanese patients than in patients from other regions (27.3% vs. 55.2%–90.0%). Furthermore, 48 different mutation types were identified. Chinese mainland and Taiwanese patients were more likely to carry the c.544A > G mutation (75% and 100%, respectively) than the patients from other regions (only 0%–10.0%). Approximately 50% of Chinese mainland patients carried the c.239C > T mutation, a much higher proportion than that found in the other populations. In addition, although the brain MRI of most patients was normal, 18F‐FDG‐PET analysis could reveal cerebellar and occipital lobe hypometabolism. Interpretation ST‐1 patients in different regions are likely to have different mutation types; environmental factors may influence clinical manifestations. Larger studies enrolling more patients are required.

PurposeBrain 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is a sensitive technique for assisting in the diagnosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. However, the common pattern of this disorder assessed by FDG PET remains unknown. The present study aimed to explore the glucose metabolic patterns of this disorder based on PET voxel analysis.MethodsThis retrospective study enrolled 25 patients with anti-LGI1 encephalitis, who were admitted in Beijing Tiantan Hospital between September 2014 and July 2019. The glucose metabolic pattern was compared between the included patients and 44 age- and gender-matched healthy controls using Statistical Parametric Mapping. Then, the correlation between the metabolic pattern and scaled activities of daily living (ADLs) of the patients was assessed.ResultsThe median time from symptom onset to PET scans was 9 w (range:2-53w). The groupwise analysis revealed that patients with anti-LGI1 encephalitis had left hippocampal hypermetabolism and hypometabolism in almost all neocortical regions. The individual-level results showed most patients presented a decreased metabolism in neocortical regions, as well as an increase in metabolism in the hippocampus and basal ganglia. Furthermore, the metabolic gradient between hippocampus and neocortical regions was positively associated with the ADLs (frontal lobe, r=0.529, P=0.008; parietal lobe, r=0.474, P=0.019; occipital lobe, r=0.413, P=0.045; temporal lobe, r=0.490, P=0.015), respectively. In addition, the patients with facio-brachial dystonic seizures (FBDS) presented bilateral putamen hypermetabolism, when compared to patients without FBDS and healthy controls.ConclusionSubcortical hypermetabolism associated with cortical hypometabolism presented with a common metabolic pattern in patients with anti-LGI1 encephalitis in the present study. The resolution of the metabolic gradient of the hippocampal hypermetabolism and neocortical hypometabolism may bring about improved clinical neurologic disability.

Objectives: In view of the concern expressed about the current references, new references for fetal biparietal diameter and head circumference should be constructed for contemporary local populations.Methods: We conducted a retrospective cross-sectional study in two hospitals in Guangdong, Southern China. Fetal biparietal diameter and head circumference percentiles regression were fitted using Cole's LMS method. The BPD and HC data were then transformed into Z-scores that were calculated using two series of reference equations obtained from two methods: Cole's LMS method and the original "mean and SD method." Each Z-score distribution was presented as the mean and standard deviation. Finally, the sensitivity and specificity of each reference for identifying fetuses 97.5th percentile (based on the observed distribution of Z-scores) were calculated. The misclassified number and Youden's index were listed.Results: A total of 17,974 biparietal diameter and 18,269 head circumference measurements were chosen to establish a reference chart. The LMS method could fit the local population better than the "mean and SD method" as it had a lower number of misclassified fetuses and a higher Youden's index.Conclusion: The Cole's LMS method was able to construct a satisfied reference range of fetal head sizes in Southern China.

Hepatitis C virus (HCV) infection greatly increases the risk of nephropathy. In this observational study, we aimed to explore the relationship between viral hepatitis infection and chronic kidney disease (CKD), identify risk factors, and determine the effect of antiviral treatment on CKD in Chinese patients with chronic HCV infection. A total of 2,435 study subjects were enrolled and divided into four groups: the HCV infection, HBV infection, HBV and HCV co-infection, and uninfected control groups. Of these, 207 patients with chronic hepatitis C (CHC) were given standard dual therapy [subcutaneous injection of recombinant interferon (IFN)-α2b and oral ribavirin (RBV)] for 48 weeks. We found that the prevalence of CKD gradually increased with age in all groups and was significantly increased in patients 60 years or older. Multivariate logistic regression analyses showed that persistent HCV infection was significantly associated with CKD [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.06–1.66; P = 0.013], whereas there was no significant link between CKD and spontaneous HCV clearance (OR, 1.23; 95% CI, 0.79–1.90; P = 0.364), HBV infection (OR, 0.73; 95% CI, 0.44–1.19; P = 0.201), or HBV/HCV co-infection (OR, 1.40; 95% CI, 0.81–2.40; P = 0.234). Notably, after anti-HCV therapy, the serum creatinine concentration was significantly decreased (76.0, 75.5–79.4 μmol/L) from the pretreatment level (95.0, 93.0–97.2 μmol/L), both in patients who showed an end of treatment virological response (ETVR) and those who did not (P 2 increased significantly (P 2 significantly decreased (P

ObjectiveIntravenous tissue plasminogen activator (tPA) is the standard therapy for patients with acute ischaemic stroke (AIS) within 4.5 hours of onset. Recent trials have expanded the endovascular treatment window to 24 hours. We investigated the efficacy and safety of using multimodal MRI to guide intravenous tPA treatment for patients with AIS of unknown time of onset (UTO).MethodsData on patients with AIS with UTO and within 4.5 hours of onset were reviewed. Data elements collected and analysed included: demographics, National Institutes of Health Stroke Scale (NIHSS) score at baseline and 2 hours, 24 hours, 7 days after thrombolysis and before discharge, the modified Rankin Scale (mRS) score at 3 months after discharge, imaging findings and any adverse event.ResultsForty-two patients with UTO and 62 in control group treated within 4.5 hours of onset were treated with intravenous tPA. The NIHSS scores after thrombolysis and/or before discharge in UTO group were significantly improved compared with the baseline (p0.05). Utilising the non-inferiority test, to compare mRS scores (0–2) at 3 months between the two groups, the difference was 5.2% (92% CI, OR 0.196). Patients in the UTO group had mRS scores of 0-2, which were non-inferior to the control group. Their incidence of adverse events was similar.ConclusionsUtilising multimodal MRI to guide intravenous only thrombolysis for patients with AIS with UTO was safe and effective. In those patients with AIS between 6 and 24 hours of time of onset but without large arterial occlusion, intravenous thrombolysis could be considered an option.

Background The associations between umbilical cord coiling, feto-placental vascular resistance and maternal blood pressure (BP) are not well understood. Method We retrospectively analyzed 502 pregnant women suspected of hypertensive disorders in the third trimester from a hospital-based cohort, who underwent ambulatory BP monitoring and umbilical artery Doppler velocimetry examinations within 14 days before delivery. By applying quantile regression, a significant quantile-dependent positive association between umbilical cord coiling index and umbilical artery pulsatility index (UAPIMOM; converted to multiples of median) was observed from above 0.75th quantiles for each parameter. Results Using the cutoffs both at the 0.75th quantile to define high umbilical cord coiling (≥0.28 coils/cm) and high UAPIMOM (≥1.30), respectively, a graded increase in BP level was observed from patients with both low, either high and both high categories. Multivariate linear and quantile regression revealed that the high umbilical cord coiling/high UAPIMOM interaction was significantly correlated with night-time mean DBP level. Moreover, umbilical cord hypercoiling (≥0.3 coils/cm) was significantly correlated with night-time DBP with an average increase of ∼5 mmHg from the 0.05th to 0.70th quantiles and independently predicted the occurrence of severe (odds ratio 2.32, 95% confidence interval: 1.22-4.41) and early-onset (odds ratio 2.43, 95% confidence interval: 1.18-4.97) preeclampsia after adjusting for covariates. Further mediation analysis showed that elevated high UAPIMOM (≥1.30) could explain 11.4% of the umbilical cord hypercoiling → high night-time DBP association. Conclusion Therefore, this retrospective study identifies excessive umbilical cord coiling, and its interaction with increased feto-placental vascular resistance, as novel risk factors for nocturnal BP elevation and preeclampsia.

Accumulative evidence demonstrates that there is an inseparable connection between inflammation and temporal lobe epilepsy (TLE). Some recent studies have found that the multifunctional microRNA-155 (miR-155) is a key regulator in controlling the neuroinflammatory response of TLE rodent animals and patients. The aim of the present study was to investigate the dynamic expression pattern of tumor necrosis factor alpha (TNF-α) as a pro-inflammatory cytokine and miR-155 as a posttranscriptional inflammation-related miRNA in the hippocampus of TLE rat models and patients. We performed real-time quantitative PCR (qRT-PCR) on the rat hippocampus 2 h, 7 days, 21 days and 60 days following kainic acid-induced status epilepticus (SE) and on hippocampi obtained from TLE patients and normal controls. To further characterize the relationship between TNF-α and miR-155, we examined the effect of antagonizing miR-155 on TNF-α secretion using its antagomir. Here, we found that TNF-α secretion and miR-155 expression levels were correlated after SE. The expression of TNF-α reached peak levels in the acute phase (2h post-SE) of seizure and then gradually decreased; however, it rose again in the chronic phase (60 days post-SE). miR-155 expression started to increase 2 h post-SE, reached peak levels in the latent phase (7 days post-SE) of seizure and then gradually decreased. The variation in the trend of miR-155 lagged behind that of TNF-α. In patients with TLE, the expression levels of both TNF-α and miR-155 were also significantly increased. Furthermore, antagonizing miR-155 inhibited the production of TNF-α in the hippocampal tissues of TLE rat models. Our findings demonstrate a critical role for miR-155 in the physiological regulation of the TNF-α pro-inflammatory response and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, regulation of the miR-155/TNF-α axis may be a new therapeutic target for TLE.

Background Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass Results and conclusions Univariate and multivariate analyses revealed that platelets9/L, albumin

The aim of our study was to investigate microRNA (miRNA) expression profiles in CD44In this study, we enriched CD44We found that CD44Our data suggest that miRNAs play important roles in regulating the stem cell-like properties of CD44

M2-like tumour-associated macrophages (TAMs) have been demonstrated to promote the growth of anaplastic thyroid carcinoma (ATC). However, the underlying mechanism of M2-like TAMs in ATC remains unclear. Thus, in the present study, the role and mechanism of M2-like TAMs in ATC were investigated. M2-like TAMs were induced by treatment with PMA, plus IL-4 and IL-13, and identified by flow cytometry. Transwell and sphere formation assays were applied to assess the invasion and stemness of ATC cells. The expression levels of insulin-like growth factor (IGF)-1 and IGF-2 were examined by ELISA and reverse transcription-quantitative PCR. Proteins related to the epithelial-mesenchymal transition (EMT), stemness and the PI3K/AKT/mTOR pathway were examined via western blotting. Immunohistochemistry (IHC) was used to detect the expression of the M2-like TAM markers CD68 and CD206 in ATC tissues and thyroid adenoma tissues. It was found that treatment with PMA plus IL-4 and IL-13 successfully induced M2-like TAMs. Following co-culture with M2-like TAMs, the invasive ability and stemness of ATC cells were significantly increased. The expression levels of the EMT-related markers N-cadherin and Vimentin, the stemness-related markers Oct4, Sox2 and CD133, and the insulin receptor (IR)-A/IGF1 receptor (IGF1R) were markedly upregulated, whereas E-cadherin expression was significantly decreased. In addition, the production of IGF-1 and IGF-2 was significantly increased. Of note, exogenous IGF-1/IGF-2 promoted the invasion and stemness of C643 cells, whereas blocking IGF-1 and IGF-2 inhibited metastasis and stemness by repressing IR-A/IGF-1R-mediated PI3K/AKT/mTOR signalling in the co-culture system. IHC results showed that the expression of CD68 and CD206 was obviously increased in ATC tissues. To conclude, M2-like TAMs accelerated the metastasis and increased the stemness of ATC cells, and the underlying mechanism may be related to the section of IGF by M2-like TAMs, which activates the IR-A/IGF1R-mediated PI3K/AKT/mTOR signalling pathway.

Background Atypical lymphocytes (AL), or reactive lymphocyte, exist in peripheral blood when stimulated by viral infection, drugs, inflammatory signals or allergens. Studies have shown that specific changes in peripheral blood (PB) analysis can predict morphological changes in blood cells. The objective of this study was to explore the value of the peripheral blood lymphocyte count in predicting the presence of AL. Methods One hundred ninety-nine outpatients were selected from Beijing Chao-Yang Hospital, Capital Medical University from January to April 2015 and underwent manual cell classification with evaluation of complete clinical data. The results of manual classification of peripheral blood leukocytes and peripheral blood routine analysis were assessed, and the correlation between peripheral blood lymphocyte counts and presence of atypical lympho-cytes evaluated using receiver operating characteristic (ROC) curves for each subject. Results Peripheral blood lymphocytes ≥ 2.375 x 109/L was found to be the optimal cutoff point for predicting atypical lymphocytes. The area under the curve (AUC), 95% confidence interval (CI), sensitivity and specificity were 0.7984, 0.7121 - 0.8846, 68.42%, and 82.8%, respectively, while the accuracy was moderate. When the proportion of peripheral blood lymphocytes was greater than 35.90%, the AUC, 95% CI, sensitivity, and specificity were 0.8729, 0.8092 - 0.9366, 89.47%, and 76.34%, respectively, while the accuracy was moderate. Conclusions The peripheral blood lymphocyte count of a patient has good predictive value for the existence of atypical lymphocytes, which is helpful for clinical diagnosis.

Background Patients positive for anti-glutamic acid decarboxylase 65 (GAD65) antibodies have attracted increasing attention. Their clinical manifestations are highly heterogeneous and can be comorbid with tumors. Currently, there is no consensus on the therapeutic regimen for anti-GAD65-associated neurological diseases due to the clinical complexity, rarity and sporadic distribution. We reported six anti-GAD65 autoimmune encephalitis (AE) patients who received intravenous methylprednisolone (IVMP) or immunoglobulin (IVIG) or both. Then, we evaluated the therapeutic effect of both by summarizing results in previous anti-GAD65 AE patients from 70 published references. Results Our six patients all achieved clinical improvements in the short term. Unfortunately, there was no significant difference between IVMP and IVIG in terms of therapeutic response according to the previous references, and the effectiveness of IVMP and IVIG was 45.56% and 36.71%, respectively. We further divided the patients into different subgroups according to their prominent clinical manifestations. The response rates of IVMP and IVIG were 42.65% and 32.69%, respectively, in epilepsy patients; 60.00% and 77.78%, respectively, in patients with stiff-person syndrome; and 28.57% and 55.56%, respectively, in cerebellar ataxia patients. Among 29 anti-GAD65 AE patients with tumors, the response rates of IVMP and IVIG were 29.41% and 42.11%, respectively. There was no significant difference in effectiveness between the two regimens among the different subgroups. Conclusion Except for stiff-person syndrome, we found that this kind of AE generally has a poor response to IVMP or IVIG. Larger prospective studies enrolling large numbers of patients are required to identify the optimal therapeutic strategy in the future.

Objectives To examine the clinical characteristics of autoimmune encephalitis associated with the glutamate decarboxylase 65 (GAD 65) antibody. Materials and methods Medical records of all patients that diagnosed with GAD 65 antibody-associated encephalitis were retrospectively analyzed. Data regarding demographics and symptoms, neurological signs, laboratory and imaging results, treatment and prognosis were collected. Results We collected a total of seven patients, mainly young or middle-aged women with a subacute or chronic course. The main clinical symptoms mainly included chronic epilepsy, cerebellar ataxia, stiff-person syndrome, and limbic encephalitis. Three of seven (43%) patients had high CSF (cerebrospinal fluid) protein levels. Oligoclonal IgG bands (including IgG 1) and 24 hours intrathecal synthesis of IgG were detected in CSF and serum in six patients, five patients (83%) reported increased distribution of oligoclonal IgG bands (including IgG 1) and 24 hours intrathecal synthesis of IgG in serum and CSF. And six of seven patients (86%) had abnormal thyroid function or were positive for thyroid antibodies. By electroencephalogram examination, sharp or slow waves in the temporal region were often observed for six of seven patients (86%). Abnormal imaging signals (six of seven patients, 86%) of the temporal lobe and hippocampus were detected by brain magnetic resonance imaging, and decreased metabolism of the temporal lobe was detected by positron emission tomography/computed tomography (six of six patients, 100%). These patients were mainly treated with corticosteroid and gamma globulin. The clinical symptoms of the patients were alleviated. Conclusions The course of GAD 65 antibody-associated encephalitis is longer than other autoimmune encephalitides. The clinical symptoms of GAD 65 autoimmune encephalitis mainly manifested as chronic epilepsy, cerebellar ataxia, stiff-person syndrome, and limbic encephalitis, and combined with or without thyroid autoimmune diseases, type 1 diabetes, and thymoma. A comprehensive understanding of the disease is a way to prevent misdiagnosis and delayed treatment.

Aims This study aims to explore the effect and underlying mechanism of zoledronic acid (ZA) on the incidence of thyroid cancer (TC) tumorigenesis. Materials and methods Human mononuclear cells THP-1 were differentiated into M2-like tumor associated macrophages (TAMs) by incubation with PMA followed by additional incubation of IL-4 and IL-13. TC cells TPC-1 and IHH4 were co-cultured with M2-like TAMs. Identification of M2-like TAMs markers were determined by immunohistochemistry or flow cytometry. Cell proliferation, stemness and migration/invasion ability were measured by colony, sphere formation assay and transwell assay, respectively. The expression levels of cell stemness, EMT and Wnt/β-catenin pathway-related factors were verified by qRT-PCR, Western blotting, and immunofluorescence. A subcutaneous tumor model was established in nude mice to examine the in vivo effects of ZA. Key findings M2-like TAMs were enriched in TC tissues, and they promoted the colony/sphere formation, accompanied with a down-regulated expression in E-cadherin and an up-regulated expression in N-cadherin, Vimentin and other stemness-associated markers (CD133, Oct4, c-Myc) in TC cells. The effects were suppressed when ZA co-treatment was given, because ZA inhibited the polarization of M2-like TAMs and β-catenin entry into the nucleus. Moreover, in agreement with in vitro data, ZA also limited subcutaneous tumor formation and macrophage enrichment in nude mice. Significance ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/β-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.

Background Recently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin‐1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS. Methods Seven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age‐matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP‐SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS. Results Independent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57‐0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study. Conclusions This study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

SummarySynaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.

The longitudinal exposure–response relationship between trimester-specific gestational weight gain (GWG) and blood pressure (BP) during pregnancy is not well understood. We retrospectively assessed 1112 uncomplicated, normotensive pregnant women whose body weight and BP were measured from 12 +0 to 40 +0 weeks of gestation from a hospital-based cohort. By using growth curve modeling, a J-shaped pattern dominated diastolic BP (DBP) changing dynamics, with a midpregnancy drop at 20 +0 to 22 +0 weeks followed by a rebound. Using group-based trajectory modeling, 3 distinctive trajectories of DBP were identified: high–J shaped (18.5%), moderate–J shaped (48.3%), and low–J shaped (33.1%), as well as 3 distinctive GWG trajectories: high increasing (14.7%), moderate increasing (48.6%) and low increasing (36.8%). A temporal coincidence between the maximal rate of GWG and DBP transition from its nadir to rebound was observed during 20 +0 to 22 +0 weeks. Moreover, women in the high-increasing GWG group had the highest probability of being in the high–J DBP group. The GWG rate during the late midsecond trimester (22 +0 to 26 +0 weeks) was consistently associated with an elevated DBP level: for every 200 g/wk increase, the multivariable-adjusted odds ratio was 1.27 (95% confidence interval, 1.13–1.43) for the trajectory shift to the high–J group and 1.20 (95% confidence interval, 1.07–1.35) for the occurrence of diastolic prehypertension after 37 +0 weeks. Furthermore, adding a trimester-specific GWG rate (22 +0 to 26 +0 weeks) contributed to the incremental yield for the prediction of diastolic prehypertension after 37 +0 weeks. Our results thus provide the timing and extent of gestational weight control relevant to the optimized BP level during pregnancy.

Background: Imbalances in gut microbiota composition are linked to hypertension, host metabolic abnormalities, systemic inflammation, and other conditions. In the present study, we examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum. Methods: Gut microbiota profiles of women with PE and healthy pregnant women in the third trimester and at 1 and 6 weeks postpartum were assessed by 16S rRNA gene amplicon sequencing. Plasma levels of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), zonulin, and lipopolysaccharide (LPS) were measured in the third trimesters. Results: At the genus level, 8 bacterial genera were significantly enriched in the antepartum samples of PE patients compared to healthy controls, of which Blautia, Ruminococcus2, Bilophila, and Fusobacterium represented the major variances in PE microbiomes. Conversely, 5 genera, including Faecalibacterium, Gemmiger, Akkermansia, Dialister, and Methanobrevibacter, were significantly depleted in antepartum PE samples. Maternal blood pressure and liver enzyme levels were positively correlated to the PE-enriched genera such as Anaerococcus, Ruminococcus2, Oribacterium, and Bilophila, while the fetal features (e.g., Apgar score and newborn birth weight) were positively correlated with PE-depleted genera and negatively correlated with PE-enriched genera. Moreover, maternal blood IL-6 level was positively associated with gut Bilophila and Oribacterium, whereas LPS level was negatively associated with Akkermansia. In terms of postpartum women, both the gut microbial composition and the PE-associated microbial alterations were highly consistent with those of the antepartum women. Conclusion: PE diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with uncomplicated pregnant women, which are associated with maternal clinical features (blood pressure level and liver dysfunction) and newborn birth weight. Moreover, these antepartum alterations in gut microbiota persisted 6 weeks postpartum.

Background Hepatitis C virus (HCV) infection is commonly associated with a disturbance of glucose metabolism. However, there have been conflicting reports on whether the clearance of the HCV may be followed by changes of serum blood glucose and insulin resistance. The aim of the present study was to evaluate the impact of HCV and antiviral treatment on serum glucose levels and other glucose metabolism parameters. Methods A retrospective analysis of 306 HCV-infected patients was performed. Fasting serum blood glucose (FBG) levels in these patients were compared with that of 325 healthy individuals. Serum parameters of glucose metabolism were measured in 183 patients with chronic hepatitis C at baseline, at the end of interferon α-2b plus ribavirin treatment, and at 24 weeks post-treatment. Results Patients with HCV infection had significantly higher FBG level than healthy controls (5.57 ± 0.74 vs. 5.11 ± 0.83 mmol/l, P

Background and purpose How to protect the ovarian function during radiotherapy is uncertain. The purpose of this study was to explore the association between the location of the transposed ovary and the ovarian dose in patients with cervical cancer received radical hysterectomy, ovarian transposition, and postoperative pelvic radiotherapy. Methods A retrospective analysis was conducted of 150 young patients with cervical cancer who received radical hysterectomy, intraoperative ovarian transposition, and postoperative adjuvant radiotherapy in Zhejiang Cancer Hospital. Association between location of the transposed ovaries and ovarian dose was evaluated. The transposed position of ovaries with a satisfactory dose was explored using a receiver operator characteristic curve (ROC) analysis. Patients’ ovarian function was followed up 3 months and 1 year after radiotherapy. Results A total of 32/214 (15%) transposed ovaries were higher than the upper boundary of the planning target volume (PTV). The optimum cutoff value of > 1.12 cm above the iliac crest plane was significantly associated with ovaries above the upper PTV boundary. When the ovaries were below the upper boundary of PTV, the optimum cutoff value of transverse distance > 3.265 cm between the ovary and PTV was significantly associated with ovarian max dose (Dmax) ≤ 4Gy, and the optimum cutoff value of transverse distance > 2.391 cm was significantly associated with ovarian Dmax≤5Gy. A total of 77 patients had received complete follow-up, and 56 patients (72.7%) showed preserved ovarian function 1 year after radiotherapy, which was significantly increased compared with 3 months (44.2%) after radiotherapy. Conclusions The location of transposed ovaries in patients with cervical cancer is significantly correlated with ovarian dose in adjuvant radiotherapy. We recommend transposition of ovaries > 1.12 cm higher than the iliac crest plane to obtain ovarian location above PTV. When the transposed ovary is below the upper boundary of PTV, ovarian Dmax ≤4Gy may be obtained when the transverse distance between the ovary and PTV was > 3.265 cm, and the ovarian Dmax≤5Gy may be obtained when the transverse distance was > 2.391 cm.

Currently, microsatellite instability (MSI) detection is limited to tissue samples with sufficient tumor content. Detection of MSI from blood has been explored but confounded by low sensitivity due to limited circulating tumor DNA (ctDNA). We developed a next-generation sequencing–based algorithm, blood MSI signature enrichment analysis, to detect MSI from blood. Blood MSI signature enrichment analysis development involved three major steps. First, marker sites that can effectively distinguish high MSI (MSI-H) from microsatellite stable tumors were extracted. Second, MSI signature enrichment analysis was performed based on hypergeometric probability, under the null hypothesis that plasma samples have similar MSI-H and microsatellite stable read coverage patterns for particular marker sites as the white blood cells from the training data set. Finally, enrichment scores of marker sites were normalized, and all markers were collectively considered to determine the MSI status of a plasma sample. In vitro dilution experiments with cell lines and in silico simulation experiments based on mixtures of MSI-H plasma and paired white blood cell DNA demonstrated 98% sensitivity and 100% specificity at a minimum of 1% ctDNA and 91.8% sensitivity and 100% specificity with 0.4% ctDNA. An independent validation cohort of 87 colorectal cancer patients with orthogonal confirmation of MSI status of tissues confirmed performance, achieving 94.1% sensitivity (16/17) and 100% specificity (27/27) for samples with ctDNA >0.4%.

Radioresistance is a crucial factor for the failure of iodine 131 (131I)-based radiotherapy for differentiated thyroid carcinoma (DTC). This study aimed to explore the effect of circ_NEK6 on the development of 131I resistance in DTC and its potential mechanism. In this study, we demonstrated that circ_NEK6 expression was significantly elevated in 131I-resistant DTC tissues and cell lines. Knockdown of circ_NEK6 significantly repressed 131I resistance via inhibiting cell proliferation, migration, invasion abilities, and inducing cell apoptosis and DNA damage in 131I-resistant DTC cells. Mechanistically, knockdown of circ_NEK6 suppressed 131I resistance in DTC by upregulating the inhibitory effect of miR-370-3p on the expression of myosin heavy chain 9 (MYH9). In vivo experiments showed that circ_NEK6 inhibition aggravated 131I radiation-induced inhibition of xenograft tumor growth. Taken together, knockdown of circ_NEK6 repressed 131I resistance in DTC cells by regulating the miR-370-3p/MYH9 axis, indicating that circ_NEK6 may act as a potential biomarker and therapeutic target for DTC patients with 131I resistance.

BACKGROUND Endometriosis can cause dysmenorrhea and infertility. Its pathogenesis has not yet been clarified and its treatment continues to pose enormous challenges. The protein tyrosine phosphatase (PTEN) gene is a tumor suppressor gene. The aim of this study was to investigate the role and significance of PTEN protein in the occurrence, development, and treatment of endometriosis through changes in apoptosis rate, cell cycle, and angiogenesis. MATERIAL AND METHODS PTEN was overexpressed and silenced in lentiviral vectors and inserted into primary endometrial cells. The changes in cell cycle and apoptosis in the different PTEN expression groups were evaluated using flow cytometry. Vessel growth mimicry was observed using 3-dimensional culture. A human-mouse chimeric endometriosis model was constructed using SCID mice. Hematoxylin and eosin staining and immunohistochemistry were used to detect pathological changes in ectopic endometrial tissues and the expression of VEGF protein in a human-mouse chimeric endometriosis mouse model. RESULTS PTEN overexpression significantly increased apoptosis and inhibited the cell cycle compared with the silenced and control groups. Furthermore, cells expressing low PTEN levels were better able to undergo vasculogenic mimicry, and exhibited significantly increased angiogenesis compared to cells overexpressing PTEN. We found that ectopic foci were more easily formed in the endometrial tissue of SCID mice with low PTEN expression, and the VEGF expression in this group was relatively high. CONCLUSIONS PTEN inhibits the occurrence and development of endometriosis by regulating angiogenesis and the apoptosis and cell cycle of endometrial cells; therefore, we propose that the PTEN gene can be used to treat endometriosis.

Background and aim Genetic variations in solute carrier (SLC) genes are associated with liver diseases, and Kruppel-like factor 12 (KLF12) affects the b chain of hemoglobin. We investigated possible correlations of SLC and KLF12 polymorphisms with viral clearance (spontaneous and treatment-induced) and adverse effects in Chinese chronic hepatitis C (CHC) patients. Methods We genotyped the single nucleotide polymorphisms in 525 CHC patients, 137 patients with spontaneous clearance, and 207 healthy controls. Three hundred fifty-seven CHC patients received recombinant interferon-alpha2b/ribavirin (IFN-α2b/RBV) treatment, and 175 patients were chosen for analysis of drug-induced cytopenia. All raw P-values were corrected by the Bonferroni method. Results A higher rate of sustained viral response was detected in patients with SLC4A11 rs3810560 CC variant versus TT/TC variant (76.9% vs 59.2%; OR, 2.42; 95% CI, 1.06–5.56, P = 0.037 after adjustment), but there was no significant difference among different hepatitis C virus genotypes. RBV-induced anemia was independently correlated with SLC29A1 rs760370 AA genotype (OR, 2.90; 95% CI, 1.29–6.54, P = 0.010), and the severity of IFN-induced thrombocytopenia was related to GG genotype (OR, 4.98; 95% CI, 1.27–19.61; P = 0.021); the detected effects held true for HCV-2a patients but weakened in HCV-1b patients. A reactive increase in platelet count was closely associated with KLF12 rs9543524 TT variant. Conclusion SLC4A11 rs3810560 polymorphism independently affected the sustained viral response rates in CHC patients, whereas SLC29A1 rs760370 and KLF12 rs9543524 single nucleotide polymorphisms correlated with treatment-induced adverse events. Clearly, the predictive power varied with HCV genotypes and the reason for genotype-dependent discrepancy was not fully understood.

Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P=0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR]=3.247, 95% confidence interval [CI]=1.038–10.159, P=0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥4×105IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P=0.034, OR [95% CI]=7.24 [1.02–318.45], negative predictive value=92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P>0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen.

Background The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. Methods In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. Results Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene. Conclusions This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction (, EXD) as a treatment for premature ovarian failure (POF) using a systems pharmacology approach.The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability (OB), drug-likeness (DL), and Lipinski's rule (LR). The active ingredients were further searched in research articles, drug targets in the DrugBank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform.A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB ⩾30% and DL ⩾0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents.The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.

Background: Recent animal studies have found that the osteocalcin secreted by osteoblasts could participate in glucose and lipid metabolism. Our study aimed to investigate the relationship between serum osteocalcin concentration and glucose and lipid metabolism in patients with type 2 diabetes mellitus. Methods: 985 patients with type 2 diabetes were divided into the male group (n = 495) and the postmenopausal female group (n = 490). The average ages were 54.42 ± 10.535 and 64.93 ± 9.277, respectively. We collected the parameters of age, duration, fasting plasma glucose, HbA1c, fasting insulin, fasting C peptide, blood lipid, 25 (OH) VD3, parathyroid hormone (PTH), Alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTx), osteocalcin, HOMA-IR, HOMA-β, body mass index (BMI), and waist-to-hip ratio (WHR). The relationship of osteocalcin and these parameters were analyzed by Pearson/Spearman correlation analysis and stepwise multiple regression analysis. Results: Osteocalcin was negatively correlated with HbA1c (p < 0.05) and it was also an independent relevant factor affecting HbA1c in both groups. Osteocalcin was positively correlated with HOMA-β and it was an independent relevant factor affecting HOMA-β in male group (p < 0.01). Conclusions: These findings indicate the association between serum osteocalcin and glucose metabolism and beta cell function. No relationship was found between osteocalcin and insulin resistance and lipid metabolism in type 2 diabetes.

The methyl methanesulfonate and ultraviolet-sensitive gene clone 81 protein is a structure-specific nuclease that plays important roles in DNA replication and repair. Knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 has been found to sensitize cancer cells to chemotherapy. However, the underlying molecular mechanism is not well understood. We found that methyl methanesulfonate and ultraviolet-sensitive gene clone 81 was upregulated and the ATM/Chk2 pathway was activated at the same time when MCF-7 cells were treated with cisplatin. By using lentivirus targeting methyl methanesulfonate and ultraviolet-sensitive gene clone 81 gene, we showed that knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 enhanced cell apoptosis and inhibited cell proliferation in MCF-7 cells under cisplatin treatment. Abrogation of ATM/Chk2 pathway inhibited cell viability in MCF-7 cells in response to cisplatin. Importantly, we revealed that ATM/Chk2 was required for the upregulation of methyl methanesulfonate and ultraviolet-sensitive gene clone 81, and knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 resulted in inactivation of ATM/Chk2 pathway in response to cisplatin. Meanwhile, knockdown of methyl methanesulfonate and ultraviolet-sensitive gene clone 81 activated the p53/Bcl-2 pathway in response to cisplatin. These data suggest that the ATM/Chk2 may promote the repair of DNA damage caused by cisplatin by sustaining methyl methanesulfonate and ultraviolet-sensitive gene clone 81, and the double-strand breaks generated by methyl methanesulfonate and ultraviolet-sensitive gene clone 81 may activate the ATM/Chk2 pathway in turn, which provide a novel mechanism of how methyl methanesulfonate and ultraviolet-sensitive gene clone 81 modulates DNA damage response and repair.

Background CXCR1 and CXCR2, cell surface receptors of interleukin-8, regulate cell migration and alteration of their expression has been associated with poor prognosis of various cancers. The aim of this study was to detect their expression in gastric cancer to identify associations with another cell adhesion molecule, matrix metalloproteinase-9 (MMP9), and with clinicopathological data ex vivo , and then explore their potential role in gastric cancer cells in vitro . Materials and methods A total of 172 cases of gastric cancer tissue specimens were collected for immunohistochemical analysis of CXCR1, CXCR2, and MMP9 expression. Expression of CXCR1 and CXCR2 proteins was knocked in or down using their cDNA and shRNA, respectively, in gastric cancer cell lines to assess the changed cell phenotypes and gene expression. Results CXCR1, CXCR2, and MMP9 were expressed in 61.0%, 77.9%, and 75.6% of gastric cancer tissues, respectively. Moreover, CXCR1 and CXCR2 expression was associated with tumor differentiations, advanced clinical stages, lymph node, and distant metastasis of gastric cancer. Similarly, MMP9 expression was associated with CXCR1 and CXCR2. Expression of these three proteins was interrelated. In vitro study showed that levels of CXCR1 and CXCR2 proteins were associated with the capacity of gastric cancer cell migration, while knockdown of their expression inhibited gastric cancer cell migration and invasion abilities in vitro . In contrast, overexpression of CXCR1 and CXCR2 proteins promoted tumor cell migration and invasion. At the gene levels, knockdown of CXCR1 or CXCR2 expression suppressed expression of Ets-1, SRC-1, and JNK proteins and phosphorylated c-Jun and Erk1/2. Conversely, upregulation of CXCR1 or CXCR2 promoted expression of Ets-1, SRC-1, JNK, and c-Jun proteins and phosphorylated JNK, c-Jun and Erk1/2. Conclusions These findings suggest that CXCR1 and CXCR2 play an important role in gastric cancer progression. Further study will be performed to investigate whether target of their expression can be used as a novel strategy in clinical control of gastric cancer metastasis.

Endometrial carcinoma (EC) is the most common malignancy in women. Dispite its prevalence, the prognosis of endometrial carcinoma still relies on conventional histological type, grade and invasion information. Its morbidity is still increasing and the outcome is very poor. To the best of our knowledge, hormonal imbalance and/or molecular genetic alterations are the main cause of EC. However, the alterations of lncRNAs which accounts for approximately 4/5 of human transcripts are still poorly understood. In the present study, using the RiboArray™ Custom Array, we studied the expression profiles of lncRNA in EC as compared to normal endometrium (NE) to find potential core lncRNAs for the diagnosis of EC. We found the potential core lncRNA by GO, KEGG, lncRNA and mRNA co-expression network. The potential functional lncRNAs were further detected by qPCR to validate the microarray results. A total of 172 lncRNAs and 188 mRNAs were found to be differentially expressed between type Ⅰ EC and the NE samples (fold change >1.5). qPCR validation showed good consistency with the microarray data. GO, pathway analysis, the lncRNA and mRNA co-expression network as well as the TCGA data revealed that 6 lncRNAs (KIAA0087, RP11-501O2, FAM212B-AS1, LOC102723552, RP11-140I24 and RP11-600K151) may be the core regulators of endometrial carcinogenesis. The potential core lncRNAs revealed by the mRNA and lncRNA co-expression network might be helpful to explore potential early diagnostic and therapeutic targets for EC.

The nonstratification of blood pressure (BP) levels may underestimate future cardiovascular risk in pregnant women who present with BP levels in the range of prehypertension (120–139/80–89 mm Hg). We prospectively evaluated the relationship between multiple antepartum BP measurements (from 11 +0 to 13 +6 weeks’ gestation to term) and the occurrence of postpartum metabolic syndrome in 507 normotensive pregnant women after a live birth. By using latent class growth modeling, we identified the following 3 distinctive diastolic BP (DBP) trajectory groups: the low-J-shaped group (34.2%; DBP from 62.5±5.8 to 65.0±6.8 mm Hg), the moderate-U-shaped group (52.6%; DBP from 71.0±5.9 to 69.8±6.2 mm Hg), and the elevated-J-shaped group (13.2%; DBP from 76.2±6.7 to 81.8±4.8 mm Hg). Notably, the elevated-J-shaped trajectory group had mean DBP and systolic BP levels within the range of prehypertension from 37 +0 and 26 +0 weeks of pregnancy, respectively. Among the 309 women who completed the ≈1.6 years of postpartum follow-up, the women in the elevated-J-shaped group had greater odds of developing postpartum metabolic syndrome (adjusted odds ratio, 6.55; 95% confidence interval, 1.79–23.92; P =0.004) than the low-J-shaped group. Moreover, a parsimonious model incorporating DBP (membership in the elevated-J-shaped group but not in the DBP prehypertension group as identified by a single measurement) and elevated levels of fasting glucose (>4.99 mmol/L) and triglycerides (>3.14 mmol/L) at term was developed, with good discrimination and calibration for postpartum metabolic syndrome ( c -statistic, 0.764; 95% confidence interval, 0.674–0.855; P

BACKGROUND Fever of unknown origin (FUO) is a common manifestation and diagnostic problem especially in primary care. Pointing out a diagnosis of FUO often requires numerous noninvasive and invasive procedures. Peripheral blood (PB) smear examination frequently provides many timely and valuable diagnostic clues in various disorders. Few assessments of PB smear morphologic examinations used in the diagnostic evaluation of FUO have been reported. METHODS To determine whether PB smears have important roles in exploring the causes of FUO, we collected PB smears of 2871 FUO patients from Beijing Chao-yang Hospital affiliated to Capital Medical University from September 2012 to August 2014. Combined with relevant clinical data, we analyzed the PB morphologic features in all the FUO patients. RESULTS We found the presence of atypical lymphocytes (64.33%), nuclear left shift (46.33%), toxic granulation, vacuolization, and 4 cases of malaria in FUO patients, markedly more than the health control group (p < 0.05), and morphologically consistent with the diagnosis of infectious diseases. Notably, the presence of blasts or immature cells in 26 cases (9%o) and the abnormal changes of leukocytes, erythrocytes or platelets in 4 cases provided predictive information for exploring the causes of FUO, followed by bone marrow smears and other procedures to further confirm the diagnosis as hematological diseases, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), Evans syndrome, agranulocytosis, immune thrombocytopenic purpura (ITP). CONCLUSIONS Our findings demonstrate that a timely and careful observing of PB smears is helpful for clarifying the diagnosis and contributes to appropriate treatment in patients with FUO.

Recent in vitro and in vivo data show that acid-sensing ion channel 1a (ASIC1a) activation enhances neuronal excitability in the hippocampus and neocortex, indicating that ASIC1a might play a role in the generation and maintenance of epileptic seizures. The aim of this study was to investigate association of the ASIC1a gene with temporal lobe epilepsy (TLE) for the first time. Six tag single-nucleotide polymorphisms (SNPs) of the ASIC1a gene were selected and genotyped using polymerase chain reaction-restriction fragment length polymorphism in 560 TLE patients and 401 healthy controls. There was a significant allelic and genotypic association between rs844347:A>C and TLE compared with controls. The rs844347-A allele frequency was 88.1% in the patients and 83.0% in control subjects (OR=1.516, 95% CI 1.142-2.013, p=0.004). Furthermore, the haplotype analysis revealed a significant association with TLE. The results of this study demonstrate for the first time an association between an ASC1a variant allele and TLE in a Han Chinese population.

This study aimed to investigate the association of the aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism, which exists in 30–50% of East Asians, and risk of acute coronary syndrome (ACS). We enrolled 1092 unrelated Han Chinese, including 546 with ACS and 546 age- and sex-matched controls. Subjects with ALDH2 mutant genotypes showed significantly higher ACS than did controls (46.7% versus 31.9%, P < 0.001). Logistic regression analysis revealed the ALDH2 mutant independently associated with ACS (odds ratio [OR] 1.95, 95% confidence interval [CI]: 1.31–2.92, P = 0.001), but the association was weaker on adjusting for alcohol consumption (OR 1.82, 95% CI: 1.23–2.70, P = 0.003). Similar results were found in a subgroup analysis of patients with primary ST-segment elevation myocardial infarction (STEMI). The ALDH2 mutant was significantly associated with level of high-sensitivity C-reactive protein (hs-CRP) in patients with ACS (P = 0.002) and in controls (P = 0.009) and number of circulating endothelial progenitor cells (EPCs) (P = 0.032); furthermore, inclusion of hs-CRP level and EPCs number as independent variables in regression analysis reduced the importance of ALDH2 polymorphism in ACS or primary STEMI. However, ALDH2 polymorphism was not associated with number of coronary arteries with significant stenosis, Gensini score or flow-mediated dilation of the brachial artery. Our results suggest that ALDH2 mutation is a genetic risk marker for ACS, which is explained in part by alcohol consumption, inflammation and number of circulating EPCs.

A recent study suggests that the P86L polymorphism (rs2986017) in the calcium homeostasis modulator 1 (CALHM1) gene interferes with calcium homeostasis and increases amyloid β (Aβ) levels. Moreover, in vitro and in vivo data show that both calcium homeostasis and high levels of Aβ play an important role in the induction and maintenance of epileptic seizures in hippocampus, indicating CALHM1 might play a potential role in pathophysiological pathways involved in temporal lobe epilepsy (TLE). The aim of this study was to investigate the genetic contribution of CALHM1 to TLE. Five single-nucleotide polymorphisms (SNPs) of CALHM1 were selected and genotyped using polymerase chain reaction restriction fragment length polymorphism in 560 patients with TLE and 401 healthy controls. We found a positive association between rs11191692 and TLE, but a negative result between rs2986017 and TLE. The rs11191692-A allele frequency was found in 32.4% of the patients and in 26.2% of control subjects (OR = 1.35, 95% CI = 1.10–1.65, uncorrected P = 0.003, corrected P = 0.015). Furthermore, the positive association between rs11191692 and TLE independent of apolipoprotein E e4 was supported by five SNPs haplotype analysis. The results of this study provide the first evidence that the SNP rs11191692 in CALHM1 confers highly increased susceptibility to TLE.

Summary Apolipoprotein E (ApoE) has been implicated as one of the susceptibility genes for temporal lobe epilepsy (TLE). Previous studies indicate that ApoE ɛ4 is associated with several disease-related traits including the increased risk of late posttraumatic seizures, earlier onset of TLE, refractory complex partial seizures, and postictal confusion. Contradictory data were also reported regarding the association between ApoE polymorphisms and TLE. The present study was designed to investigate whether ApoE ɛ4 is a risk factor for TLE and the above clinical variables, as well as to determine whether −491A/T polymorphism may independently alter the risk for TLE in a Chinese Han population. The ApoE and −491A/T polymorphisms were genotyped in 558 controls and 735 patients including 560 TLE patients using polymerase chain reaction-restriction fragment length polymorphism. A significant association was detected between prior trauma and the ApoE ɛ4 allele in TLE patients. However, no significant differences were observed in the genotype and haplotype distributions and allele frequencies of these two polymorphisms between cases and controls. Furthermore, there were no significant associations between these two polymorphisms and the other clinical variables examined. The study illustrates that the ApoE ɛ4 allele may be involved in the development of TLE in those patients with prior trauma in the Chinese Han population.

It is rare for a study to address immediate metabolic change in pre-eclamptic pregnancy. Our aim is to study the ante-partum and post-partum metabolic markers in pre-eclampsia. A total of 33 pre-eclamptic and 200 uncomplicated women with singleton pregnancies were recruited for the prospective research. Immediately ante-partum and 24–48 h postpartum venous blood samples were collected for the analysis of metabolic markers. In the pre-eclamptic group, the ante-partum fasting glucose, fasting insulin, triglyceride and free fatty acid levels were found to be higher than in the control group; however, ante-partum high-density lipoprotein level was lower. Interestingly, fasting glucose and insulin levels decreased by 24–48 h post-partum in both groups and no significant differences were found. Pre-eclamptic patients had lower post-partum high-density lipoprotein (P=0.02), higher triglyceride (P

The Impact of Pediatric Epilepsy Scale (IPES) is an accurate, acceptable, and quick tool that assesses the impact of epilepsy on the child with epilepsy and his or her family. The aim of this study was to investigate its applicability in China. After multistage translation and cultural adaptation, the final Chinese version was administered to 110 parents of children with epilepsy to evaluate its validity, reliability, and sensitivity. All items contributed significantly to the summary measure. With respect to validity, all items were substantially correlated with the criterion questionnaire subscales, and principal component analysis indicated that three factors accounted for 72% of the variance of the scale. The internal consistency coefficients of the first and second tests for the total were 0.916 and 0.930, respectively, and test–retest reliability ranged from 0.891 to 0.992. Additionally, the IPES can detect differences in health-related quality of life (HRQOL) between subjects according to epilepsy severity. In conclusion, this study indicates that the Chinese IPES has good validity, reliability, and sensitivity, and is an epilepsy-specific HRQOL questionnaire that is a brief, accurate, and valid assessment of the influence of epilepsy on the child and family.

Background Fuyu city in China has a high prevalence of hepatitis C virus (HCV) infection resulting in a high morbidity and mortality from chronic liver disease and hepatocellular carcinoma. This study was conducted to identify the risk factors for HCV infection in Fuyu city. Methods Recruitment of study subjects involved a cross-sectional survey using non-random, convenience sampling. Information on demographic variables, risk factors for HCV infection, clinical manifestations, behavioral practices and family history was collected by administering a questionnaire. Anti-HCV antibody was detected using Abbott ARCHITECT i2000SR. HCV infection was confirmed by HCV-RNA testing by the Roche Taqman HCV test. Univariate and multivariate analyses were performed to identify the factors associated with HCV infection. Results Out of 3,228 persons that participated in the survey, 3,219 were enrolled in the study. The prevalence of HCV infection was 42.1 % (1355/3219). Among 734 patients with chronic HCV infection whose HCV-RNA genotyping was performed, genotype 1b was the most common (58.0 %), followed by genotype 2a (40.2 %), while co-infection with genotypes 1b and 2a was detected in 1.8 % of the subjects. On univariate analysis, male gender, older age, parenteral caffeinum natrio-benzoicum and share syringes (PCNBSS), and nine other factors were significantly associated with HCV infection. After adjusting for potential confounders, male gender, old age, cigarette smoking, lower education level, history of blood transfusion, blood donation, prior dental surgery, and PCNBSS were found to be independently associated with HCV infection. Conclusions The prevalence of HCV infection is likely to be high among residents in Fuyu and we observed that genotypes 1b and 2a dominated in the city. Our findings support the hypothesis that PCNBSS which became endemic in Fuyu city during 1970s-1980s is strongly associated with HCV positivity. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-2299-8) contains supplementary material, which is available to authorized users.

Background Some recent studies suggest that some imaging-negative temporal lobe epilepsy (TLE) had significant amygdala enlargement (AE). Contradictory data were also reported in previous studies regarding the association between AE and TLE. The present study was to investigate the clinical characters of a group of TLE with AE and compare the amygdala volume of the same patient before and after antiepileptic drugs treatment by a larger sample size. Methods This study recruited 33 mesial TLE patients with AE and 35 healthy volunteers. The clinical history, seizure semiology, electroencephalogram (EEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) and amygdala volume were investigated. The amygdala volume were compared between ipsilateral and contralateral sides, TLE patients and 35 healthy controls, and patients at first and follow-up visit by 3.0 T MRI. Results Average seizure onset age was 42.0 years (SD 14.3). All patients had complex partial seizures, fourteen had occasional generalized tonic-clonic seizures which often happened during sleep. Ninety percent patients suffered from anxiety or depression. Thirty percent patients had memory decline. Interictal epileptiform discharges appeared predominantly in the anterior or inferior temporal area ipsilateral to AE. Interictal FDG-PET showed regional glucose hypometabolism in the ipsilateral temporal lobe. No hippocampal sclerosis (HS) was suspected in all patients. 22 patients demonstrated good seizure control and significantly reduced volume of the enlarged amygdala after treatment (P

Context:Clinical evidence on the consequential effects of continuous glucose monitoring (CGM) on pregnancy outcomes in women with gestational diabetes mellitus (GDM) is scarcely available.Objective:Our objective was to evaluate the effectiveness of CGM on maternal glycemic control and pregnancy outcomes in patients with GDM .Patients:In total, 340 Chinese pregnant women with GDM were allocated to either the routine care group (n = 190) or the CGM group (n =150).Design and Setting:This was a prospective cohort study in the Department of Obstetrics of GuangDong Women and Children Hospital in China. Recruitment started in April 2011 and stopped in August 2012.Interventions:A 72-hour CGM system was used as a supplementary tool for glucose monitoring in the CGM group.Primary Outcome Measurements:The parameters of glycemic variability included mean blood glucose, the SD of blood glucose, mean amplitude of glycemic excursions (MAGEs), and the mean of daily differences. The maternal outcomes (preeclampsia and cesarean delivery) and composite neonatal outcomes were analyzed.Results:The SD of blood glucose, MAGEs, and mean of daily differences values were significantly lower in the CGM group compared with those of the routine care group (P < .001). Subjects in the CGM group were at lower risk of preeclampsia and primary cesarean delivery compared with the routine care group (P < .05). The mean infant birth weight of women in the CGM group was lower than infants of women in the routine care group (P < .001). The MAGE was associated with birth weight (β = 0.196, P < .001), and it was an independent factor for preeclampsia (odds ratio, 3.66; 95% confidence interval 2.16–6.20) and composite neonatal outcome (odds ratio, 1.34; 95% confidence interval 1.01–1.77).Conclusions:The use of supplementary CGM combined with routine antenatal care can improve the glycemic control and pregnancy outcomes of patients with GDM.

To explore the adjuvant effects of Mycobacterium tuberculosis heat shock protein (TBhsp) and Mycobacterium tuberculosis T cell stimulatory epitope (MT) in the preparation of the monoclonal antibody (mAb) against phosphatase of regenerating liver-3 (PRL-3).The prokaryotic expression vectors pET28a were used for the construction of pET28a-PRL-3 (control plasmids), pET28a-PRL-3-MT, pET28a-TBhsp-PRL-3 and pET28a- TBhsp-PRL-3-MT (recombinant plasmids). The various fusion proteins expressed in bacteria were purified and utilized to immunize the BALB/c mice, respectively. The serum level of specific anti-PRL-3 antibody was measured by ELISA. The mouse with the highest serum level of anti-PRL-3 antibody was selected to prepare mAb with hybridoma technique. The subclasses of mAb were identified.The PRL-3 fusion proteins expressed from the four expression plasmids were purified successfully. The serum level of anti-PRL-3 antibody from the mice immunized with PRL-3-MT was the highest compared with the other immune groups. Ten hybridoma cell lines secreting anti-PRL-3 mAb were obtained after cell fusion and ELISA primary screening, and all of the mAb subclasses were IgG.MT is a potentially effective molecular adjuvant in preparation of mAb specific for PRL-3.

Hepatitis C virus (HCV) infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.