Circulating small extracellular vesicle-based miRNA classifier for follicular thyroid carcinoma: a diagnostic study.

BACKGROUND: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. METHODS: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. RESULTS: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. CONCLUSIONS: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Association Between the Serum α-Klotho Level and Insulin Resistance in Adults: NHANES 2007-2016.

OBJECTIVE: This study aimed to investigate the relationship between serum α-Klotho levels and insulin resistance (IR), a precursor to type 2 diabetes. METHODS: The study analyzed data from 4,758 adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. The relationship between α-Klotho concentration and IR was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and odds ratios (OR) derived from logistic regression models. RESULTS: Results showed that every 1-ln increase in α-Klotho concentration raised the HOMA-IR value by 0.55 (95% confidence interval 0.35-0.74) and the odds of IR by 64% (odds ratio 1.64; 95% confidence interval 1.28-2.1). The odds of IR was 40% greater in highest tertile than in the lowest tertile. CONCLUSION: The findings of this study underscore a significant correlation between increased serum α-Klotho levels and the prevalence of IR.

A comparative study on ctDNA and tumor DNA mutations in lung cancer and benign cases with a high number of CTCs and CTECs.

BACKGROUND: Liquid biopsy provides a non-invasive approach that enables detecting circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) using blood specimens and theoretically benefits early finding primary tumor or monitoring treatment response as well as tumor recurrence. Despite many studies on these novel biomarkers, their clinical relevance remains controversial. This study aims to investigate the correlation between ctDNA, CTCs, and circulating tumor-derived endothelial cells (CTECs)  while also evaluating whether mutation profiling in ctDNA is consistent with that in tumor tissue from lung cancer patients. These findings will help the evaluation and utilization of these approaches in clinical practice. METHODS: 104 participants (49 with lung cancer and 31 with benign lesions) underwent CTCs and CTECs detection using integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy. The circulating cell-free DNA (cfDNA) concentration was measured and the mutational profiles of ctDNA were examined by Roche AVENIO ctDNA Expanded Kit (targeted total of 77 genes) by next generation sequencing (NGS) in 28 patients (20 with lung cancer and 8 with benign lesions) with highest numbers of CTCs and CTECs. Mutation validation in matched tumor tissue DNA was then performed in 9 patients with ctDNA mutations using a customized xGen pan-solid tumor kit (targeted total of 474 genes) by NGS. RESULTS: The sensitivity and specificity of total number of CTCs and CTECs for the diagnosis of NSCLC were 67.3% and 77.6% [AUC (95%CI): 0.815 (0.722-0.907)], 83.9% and 77.4% [AUC (95%CI): 0.739 (0.618-0.860)]. The concentration of cfDNA in plasma was statistically correlated with the size of the primary tumor (r = 0.430, P = 0.022) and CYFRA 21-1 (r = 0.411, P = 0.041), but not with the numbers of CTCs and CTECs. In this study, mutations were found to be poorly consistent between ctDNA and tumor DNA (tDNA) in patients, even when numerous CTCs and CTECs were present. CONCLUSION: Detection of CTCs and CTECs could be the potential adjunct tool for the early finding of lung cancer. The cfDNA levels are associated with the tumor burden, rather than the CTCs or CTECs counts. Moreover, the poorly consistent mutations between ctDNA and tDNA require further exploration.

Diagnostic performance of noncultural methods for central nervous system aspergillosis.

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.

Trends, Influence Factors, and Doctor-Patient Perspectives of Web-Based Visits for Thyroid Surgery Clinical Care: Cross-Sectional Study.

BACKGROUND: In recent years, the new generation of telecommunication technologies has profoundly changed the traditional medical industry. To alleviate the medical difficulties faced by patients with thyroid diseases, hospitals have opened web-based visits and actively combined online-to-offline outpatient services. OBJECTIVE: This study aims to explore differences between office and web-based outpatient services from doctors' and patients' perspectives, illustrate the effect of the COVID-19 pandemic on outpatient services, and provide clues for improving the online-to-offline mode of care for patients with thyroid diseases. METHODS: We collected the complete web-based and office outpatient records of the Thyroid Surgery Center of West China Hospital. A total of 300,884 completed patient encounters occurred (201,840 office visits and 99,044 web-based visits) from January 1, 2019, to May 31, 2022. We performed logistic regression to evaluate the association between the chosen visit type and patients' sociodemographic characteristics. RESULTS: The number of web-based visits rapidly increased since March 2020 and reached 45.1% (4752/10,531) of all encounters in December 2021. The COVID-19 pandemic dramatically accelerated the development of web-based visits. Web-based visits were preferred by patients 18-45 years old (odds ratio [OR] 2.043, 95% CI 1.635-2.552, P<.001), patients with relatively high-paying jobs (technical staff: OR 1.278, 95% CI 1.088-1.479, P=.003; office clerk: OR 1.25, 95% CI 1.07-1.461, P=.005; national public servant: OR:1.248, 95% CI 1.042-1.494, P=.02), and patients living in Sichuan Province (excluding Chengdu; OR 1.167, 95% CI 1.107-1.23, P<.001). The medicine cost (P<.001) and examination cost (P<.001) of office visits were significantly higher than those of web-based visits. CONCLUSIONS: Web-based outpatient visits have increased rapidly in recent years, and the COVID-19 pandemic has boosted their development. The preference for web-based visits was influenced by the socioeconomic and demographic characteristics of both patients and doctors.

Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway.

BACKGROUND: Part of papillary thyroid microcarcinoma (PTMC) has a high risk of tumor invasion and metastasis, which may occur in the regional lymph node metastasis or distant metastasis, severely threatening the life of patients. Invasion and metastasis are tightly involved in the proliferation, migration and invasion in cancer. This study aimed to investigate the role of tescalcin (TESC) in the proliferation, migration and invasion of PTMC. METHODS: The expressions of TESC in PTMC tissues and cells were detected by immunohistochemistry or qRT-PCR. Then, TPC-1 and BHT101 cells transfected with TESC-RNAi were used for the transcriptome sequencing. The proliferation, apoptosis, migration and invasion of TPC-1 and BHT101 cells were detected by CCK-8, colony formation, flow cytometric assay, transwell migration and scratch test. Moreover, TESC-RNAi transfected TPC-1 and BHT101 cells were subcutaneously injected into mice. Tumor volume and weight were calculated, and the positive rate of Ki-67 was determined by immunohistochemistry. Finally, the levels of c-Fos, ERK1/2 and p-ERK1/2 were determined by western blot. RESULTS: The expressions of TESC in PTMC tissues and cell lines were prominently enhanced. Transcriptome sequencing results showed that c-Fos was decreased in TPC-1 and BHT101 cells transfected with TESC-RNAi, which was associated with multiple different signaling pathways including the MAPK signaling pathway. Furthermore, TESC promoted the progress of PTMC by regulating the expression of c-Fos, which might be associated with the ERK signaling pathway. CONCLUSIONS: TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.

The study of bone mineral density measured by quantitative computed tomography in middle-aged and elderly men with abnormal glucose metabolism.

BACKGROUND: To investigate the value of quantitative computed tomography (QCT) measurement of bone mineral density (BMD) in middle-aged and elderly men with abnormal blood glucose. METHODS: Total 138 men aged above 50 years old with routine physical examination were involved in the study. All participants were evaluated with serological index, BMD by QCT and dual energy X-ray absorptiometry (DXA). Statistical analysis was conducted by χ2 test and regression model. RESULTS: All individuals were divided into normal blood glucose (NBG) group and abnormal blood glucose (ABG) group. Compared with NBG group, BMD detected by QCT was obviously lower in ABG group (P < 0.05). More cases with low bone mass or osteoporosis were detected by QCT measurement than DXA (χ2 = 56.618, P = 0.000), which were consistent in both NBG and ABG groups (χ2 was 33.564 and 23.250, P = 0.000). No significant difference of detection rates was found in both subgroups neither by QCT nor DXA measurement (χ2 = 4.204, P = 0.122). Regression analysis revealed that ABG was negatively associated with BMD assessed by QCT (ß = -0.217, P < 0.05), which did not show statistical difference after adjusting for age. CONCLUSION: In middle-aged and elderly male patients with NBG or ABG, QCT manifests higher detection rates of low bone mass and osteoporosis than DXA. ABG is negatively correlated with BMD measured by QCT, which is affected by age.

Change of vitamin D status and all-cause mortality among Chinese older adults: a population-based cohort study.

BACKGROUND: The association of vitamin D with all-cause mortality remains controversial and longitudinal evidence exploring the potential effects of change in vitamin D status is limited in the oldest old (aged ≥ 80 years old). We aimed to study the relationship between vitamin D change and all-cause mortality among older Chinese adults including the oldest old. METHODS: The data of Chinese Longitudinal and Health Longevity Study in 2012 and 2014 wave was used for baseline data. Mortality was assessed in the subsequent 2018 survey waves. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality related to vitamin D change, including maintaining deficiency or no deficiency, deficiency to no deficiency, and no deficiency to deficiency, using below 50 nmol/L as definition of deficiency. RESULTS: The mean age of the total 1362 participants was 84.4 ± 12.1(60-113) years. The prevalence of vitamin D deficiency was 67.5% and 68.4% in 2012 and 2014 wave respectively, and significantly differed by sex and age at baseline. Cox regression showed that participants with deficiency to no deficiency and maintaining no deficiency of vitamin D status had decreased HR for all-cause mortality, compared to the maintaining deficiency group. The HRs for mortality were 0.70(95%CI: 0.50-0.96, p = 0.028) and 0.47(95%CI: 0.33-0.68, p < 0.001) respectively in the adjusted model. Also, females and the oldest old had a greatest reduction in mortality risk. And no significant difference in mortality in the no deficiency to deficiency group. CONCLUSIONS: Not only maintaining no deficiency, but also the change from deficiency to no deficiency of vitamin D status were associated with lower risk of all-cause mortality, especially in the female and oldest-old participants initially with low vitamin D level.

Conspicuousness and recurrence related factors of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules.

OBJECTIVE: Microwave ablation (MWA) is a minimally invasive technique for the treatment of benign thyroid nodules. The purpose of this study was to evaluate efficacy and safety of ultrasound-guided MWA in the treatment of benign thyroid nodules, and to find out the recurrence related factors, so as to provide reference for future clinical work. METHODS: This study retrospectively analyzed the patients who received ultrasound-guided MWA for benign thyroid nodules in our hospital from October 2018 to March 2020. A total of 214 patients were included in the study. We assessed thyroid volume changes (represented by volume reduction ratio VRR), the energy per 1 mL reduction in nodular volume (represented by energy volume ratio ΔE), the serum levels of free triiodide thyroid hormone (FT3), free thyroxine (FT4), thyrotropin (TSH) and complications after MWA treatment. RESULTS: There were a total of 306 nodules in 214 patients, including 183 (85.51%) females and 31 (14.49%) males. The median diameter and volume of the nodule were 33 mm and 8.01 mL. The VRR at 1 month, 3 months, 6 months and 12 months were 40.79%, 60.37%, 74.59% and 85.60%, respectively. In addition, MWA had a better ablation effect for small nodules (initial volume ≤ 10 mL). In recurrent studies, we found that ΔE was an independent risk factor for benign thyroid nodules (P < 0.05). CONCLUSIONS: Ultrasound-guided MWA is effective and safe in the treatment of benign thyroid nodules. In addition, it has little damage to surrounding tissues and no effect on thyroid function. Especially, the nodules with smaller initial volume, the treatment is better. On the other hand, the energy per 1 mL reduction ΔE in nodular volume may be associated with nodular recurrence, which requires further follow-up for longer periods. At this stage, we consider that ultrasound-guided MWA can be used as one of the main clinical treatment methods for benign thyroid nodules.

Pseudorabies virus encephalitis in humans: a case series study.

Pseudorabies virus (PRV) is known to cause severe encephalitis in juvenile pigs and various non-native hosts; recent evidences suggest that PRV might cause encephalitis in humans. In a multicenter cohort study in China, next-generation sequencing of cerebrospinal fluid (CSF) was performed to detect pathogens in all patients with clinically suspected central nervous system infections. This study involved all the patients whose CSF samples were positive for PRV-DNA; their clinical features were evaluated, and species-specific PCR and serological tests were sequentially applied for validation. Among the 472 patients tested from June 1, 2016, to December 1, 2018, six were positive for PRV-DNA, which were partially validated by PCR and serological tests. Additionally, we retrospectively examined another case with similar clinical and neuroimaging appearance and detected the presence of PRV-DNA. These patients had similar clinical manifestations, including a rapid progression of panencephalitis, and similar neuroimaging features of symmetric lesions in the basal ganglia and bilateral hemispheres. Six of the patients were engaged in occupations connected with swine production. PRV infection should be suspected in patients with rapidly progressive panencephalitis and characteristic neuroimaging features, especially with exposure to swine.

Isolation and culture of rat aortic endothelial cells in vitro: A novel approach without collagenase digestion.

To study cardiovascular diseases, the isolation and culture of functional endothelial cells are very important. This study uncovered a novel approach to isolate and culture endothelial cells. The thoracic aorta was collected from Wistar rats with the attached tissue clearly removed. These aorta segments were seeded onto a six-welled plate with the endothelium facing down and removed 2 days after endothelial sprouting started. The endothelial cells were harvested until 80% uneven confluence and cultured for another two passages for use in the following assays: immunofluorescence and flow cytometry assays for endothelial marker expression (CD31 and von Willebrand factor [vWF]), the Dil-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assay, the tube formation assay, the Hoechst staining apoptosis assay, the ß-galactosidase staining assay for cell senescence, and the Cell Counting Kit-8 (CCK-8) assay for cell viability. Morphologically, the endothelial cells started to migrate away from the aorta after 50 to 72 hours of culture, showing a cobblestone-like structure. The cultured cells expressed high levels of CD31 and vWF, 94.65% of the cells were positive for CD31, and most of the cells showed low-density lipoprotein uptake. They were able to form tube-like structures in vitro and were negatively stained for ß-galactosidase or Hoechst staining. Importantly, the cells at passages 3 and 10 showed similar levels of CCK-8, ß-galactosidase, Hoechst staining, uptake of Dil-Ac-LDL, and capillary tube formation. This novel technique is useful to isolate and culture rat aortic endothelial cells for future studies of endothelial functions and biology. In addition, primary vascular endothelial cells at passages 3 to 10 are suitable for experiments.

The effect and mechanism of millepachine-disrupted spindle assembly in tumor cells.

Millepachine (MIL) is a bioactive natural product that shows great potential for cancer treatment. Previous studies showed that MIL was a novel cancer drug candidate with a special structure. To provide reference for the research and development of MIL, we further investigated the mechanism of MIL inducing G2/M arrest and found MIL disrupted spindle assembly in tumor cells. In this study, we investigated the disrupting spindle assembly effects of MIL with a focus on its potential mechanism of action. First, we indicated that MIL did not inhibit microtubule polymerization from the results of in-vivo microtubule nucleation assay and microtubule polymerization in-vitro assay but delayed this process by inhibiting the production of ATP in tumor cells. Thereafter, we investigated the effect of MIL on the mitotic spindle. We found that MIL induced multipolar spindles by inhibiting the activity of Eg5 and inhibited mitotic spindle formation and chromatin condensation by the activation of the spindle assembly checkpoint (SAC) in tumor cells. These results established a novel function of MIL in regulating the assembly of mitotic spindle. As Eg5 and SAC are antitumor targets, effect of MIL on the Eg5 protein and SAC activation hinted that MIL has novel application in the development of antitumor drugs.

Next generation sequencing based pathogen analysis in a patient with neurocysticercosis: a case report.

BACKGROUND: Accurate and early diagnosis of neurocysticercosis (NCC) remains a challenge due to the heterogeneity of its clinical, immunological and imaging characteristics. The presence of cysticercus DNA in cerebrospinal fluid (CSF) of NCC patients has been previously detected via conventional PCR assays. To the best of our knowledge, the use of CSF Next-Generation Sequencing (NGS) based pathogen analysis in patients with NCC infection has never been reported. CASE PRESENTATION: This study reports the clinical, imaging, and immunological features of a patient initially presenting with several months of headache who further developed a pure sensory stroke. NGS was used to detect the pathogen, and her CSF demonstrated the presence of Taenia solium-DNA. This finding was confirmed by a positive reaction to CSF cysticercosis antibodies. After antiparasitic treatment, secondary CSF NGS revealed the DNA index have dropped considerably compared to the initial NGS readings. CONCLUSIONS: NGS is a promising tool for the early and accurate diagnosis of central nervous system (CNS) infection, especially in the setting of atypical clinical manifestations. Further studies are required to evaluate the persistence of DNA in the CSF of patients.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors as add-on to metformin and sulfonylurea treatment for the management of type 2 diabetes: a meta-analysis.

This study evaluates the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors as add-on to metformin and sulfonylurea treatment for type 2 diabetes management. The literature search was conducted in electronic databases and meta-analyses of mean differences in the changes from baseline in selected disease endpoints (efficacy endpoints) or odds ratios (for safety endpoints) were performed to compare outcomes between SGLT2 inhibitor- and placebo-/comparator-treatments. Seven studies (5,143 patients; age 56.75 years [95% CI: 56.19, 57.37]; body mass index 29.53 kg/m2 [28.23, 30.83]; and 51.87% [50.46, 53.57] males) were included. Compared to placebo, SGLT2 inhibitors significantly (p < 0.00001) reduced glycated hemoglobin (HbA1c; -0.79% [95% CI: -0.90, -0.68]), fasting plasma glucose (FPG; -1.73 mmol/L [-1.86, -1.60]) and body weight (-1.85 kg [-2.11, -1.59]) after 52-78 weeks of treatment. There were no significant differences in reduction of either HbA1c, FPG or body weight between 18-24 weeks and after 52-76 weeks of treatment. Treatment with SGLT2 inhibitors as add-on to metformin and sulfonylurea was also associated with significant reductions in blood pressure and triglycerides and increase in high-density lipoprotein-cholesterol. Incidence of hypoglycemia was significantly higher, but incidence of hyperglycemia was significantly lower in SGLT2 inhibitor group. Overall, drug-related adverse events were more common in SGLT2 group mainly due to higher incidence of genital tract infections.

Detection of virus in CSF from the cases with meningoencephalitis by next-generation sequencing.

We screened for viral DNA in cerebrospinal fluid samples using next-generation sequencing (NGS) technology to diagnose CNS viral infections. We collected CSF samples from four cases with clinically suspected viral meningoencephalitis. DNA extracted from the samples was analyzed with NGS, and the results were further validated using PCR. Herpes simplex virus 1 (HSV-1) was detected in the CSF of two patients, HSV-2 and human herpes virus type 3 (HHV-3, VZV) in the CSF of two other patients separately. The number of unique reads of the identified viral genes ranged from 144 to 44205 (93.51 to 99.57%). The coverage of identified viral genes ranged from 12 to 98% with a depth value of 1.1 to 35, respectively. The results were further confirmed using PCR in three cases. The clinical presentation and outcomes of these four cases were consistent with the diagnostic results of NGS. NGS of CSF samples can be used as a diagnostic assay for CNS viral infection. Its further application for "pan-viral" or even "pan-microbial" screening of CSF might influence the diagnosis of CNS infectious diseases.

Ultrasound-Guided Diffuse Optical Tomography for Predicting and Monitoring Neoadjuvant Chemotherapy of Breast Cancers: Recent Progress.

In this manuscript, we review the current progress of utilizing ultrasound-guided diffuse optical tomography (US-guided DOT) for predicting and monitoring neoadjuvant chemotherapy (NAC) outcomes of breast cancer patients. We also report the recent advance on optical tomography systems toward portable and robust clinical use at multiple clinical sites. The first patient who has been closely monitored before NAC, at day 2, day 8, end of first three cycles of NAC, and before surgery is given as an example to demonstrate the potential of US-guided DOT technique.

[The Risk Factors of Contralateral Central Lymph Node Metastasis in Solitary Thyroid Papillary Micro-carcinoma].

OBJECTIVE: To explore the possible risk factors of contralateral central lymph node metastasis (CLNM) in solitary thyroid papillary micro-carcinoma (PTMC). METHODS: Clinicopathologic data of 318 patients with confirmed solitary PTMC by final histological who underwent bilateral centeral lymph node dissection (CLND) from April 2012 to May 2015 in our hospital were retrospectively reviewed. Univariate Χ2 test and multivariate logistic regression analysis were used to determine the risk factors of contralateral CLNM in solitary PTMC. RESULTS: The incidence of ipsilateral CLNM and contralateral CLNM in solitary PTMC patients were 40.57% (129/318), 9.75% (31/318), respectively. Univariate analyses revealed that contralateral CLNM had a correlation with tumor located in lower pole, capsular invasionand underlying ipsilateral CLNM (P < 0.05), and had a correlation with underlying nodular goiter (P < 0.05). Multivariate logistic regression analysis showed that tumor located in lower pole and ipsilateral CLNM were independent risk factors for contralateral CLNM (P < 0.05). CONCLUSIONS: Solitary PTMC patients had a low tendency to contralateral CLNM, it shouldn't undergo contralateral CLND commonly, if the tumor located in lower pole or combine withipsilateral CLNM, it should be consider to undergo bilateral CLND.

Metabolic diseases and sex hormone levels affect differently in the development of cardiovascular and cerebrovascular diseases in elderly males.

OBJECTIVE: This single-centre cross-sectional study aimed to investigate the metabolic and gonadal risk factors of vascular diseases in elderly males. METHODS: After screening, 337 subjects aged 60-90 were found to be qualified. Odds ratios (ORs) in cross-table analyses and exp(B) in logistic regression analyses were used to evaluate the vascular risk of dependent factors. R(2) of logistic regression equation was used to estimate the goodness-of-fit of vascular diseases logistic regression models. RESULTS: Hypertension increased the risk of cardiovascular disease (CAVD) in elderly men approximately 3-fold. The number of metabolic diseases also correlated with incremental risks of CAVD; presence of one abnormality approximately increases the risk approximately 62%. Cerebrovascular disease (CEVD) development was closely associated with both metabolic syndrome and sex hormone levels; their explanation effects of single action and combined action were 13.2%, 12.55% and 28.5%. C-peptide might be the underlying mechanism of the metabolic syndrome's effect on CEVD. C-peptide = 2.43 U/L and FE(2) = 0.66 were the tangent points in receiver operating characteristic (ROC) analyses. CONCLUSIONS: Metabolic diseases and sex hormones play different roles in the development of CAVD and CEVD, the methods for vascular protection in elderly men should be promoted differently according to the their risks of CAVD and CEVD.