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Existing studies have confirmed the accuracy of arterial spin labeling (ASL) in differentiating between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). We aimed to consolidate the existing evidence with a meta-analysis. Six literature databases were searched for relevant papers. After assessing the quality of studies, bivariate regression was performed, and the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were calculated, along with the corresponding 95% confidence intervals (CIs). Deeks’ test was used to determine risk of publication bias. Ten high-quality studies, comprising 151 patients with PCNSL and 455 with HGG, were included. The pooled SEN was 0.79 (95% CI: 0.72–0.85), pooled SPE was 0.90 (95% CI: 0.84–0.94), pooled PLR was 8.07 (95% CI: 5.01–13.02), pooled NLR was 0.23 (95% CI: 0.17–0.32), pooled diagnostic score was 3.56 (95% CI: 2.94–4.18), and pooled DOR was 35.10 (95% CI: 18.83–65.45). The AUC of SROC was 0.86 (95% CI: 0.83–0.89). No publication bias was found. ASL demonstrated high diagnostic accuracy in differentiating between PCNSL and HGG.

The raphe nuclei comprise nearly all of 5-hydroxytryptaminergic (5-HTergic) neurons in the brain and are widely acknowledged to participate in the modulation of neural excitability. "Excitability-inhibition imbalance" results in a variety of brain disorders, including epilepsy. Epilepsy is a common neurological disorder characterized by hypersynchronous epileptic seizures accompanied by many psychological, social, cognitive consequences. Current antiepileptic drugs and other therapeutics are not ideal to control epilepsy and its comorbidities. Cumulative evidence suggests that the raphe nuclei and 5-HTergic system play an important role in epilepsy and epilepsy-associated comorbidities. Seizure activities propagate to the raphe nuclei and induce various alterations in different subregions of the raphe nuclei at the cellular and molecular levels. Intervention of the activity of raphe nuclei and raphe 5-HTergic system with pharmacological or genetic approaches, deep brain stimulation or optogenetics produces indeed diverse and even contradictory effects on seizure and epilepsy-associated comorbidities in different epilepsy models. Nevertheless, there are still many open questions left, especially regarding to the relationship between 5-HTergic neural circuit and epilepsy. Understanding of 5-HTergic network in a circuit- and molecule-specific way may not only be therapeutically relevant for increasing the drug specificity and precise treatment in epilepsy, but also provide critical hints for other brain disorders with abnormal neural excitability. In this review we focus on the roles of the raphe 5-HTergic system in epilepsy and epilepsy-associated comorbidities. Besides, further perspectives about the complexity and diversity of the raphe nuclei in epilepsy are also addressed.

Group testing (or pool testing), for example, Dorfman’s method or grid method, has been validated for COVID-19 RT-PCR tests and implemented widely by most laboratories in many countries. These methods take advantages since they reduce resources, time, and overall costs required for a large number of samples. However, these methods could have more false negative cases and lower sensitivity. In order to maintain both accuracy and efficiency for different prevalence, we provide a novel pooling strategy based on the grid method with an extra pool set and an optimized rule inspired by the idea of error-correcting codes. The mathematical analysis shows that (i) the proposed method has the best sensitivity among all the methods we compared, if the false negative rate (FNR) of an individual test is in the range [1%, 20%] and the FNR of a pool test is closed to that of an individual test, and (ii) the proposed method is efficient when the prevalence is below 10%. Numerical simulations are also performed to confirm the theoretical derivations. In summary, the proposed method is shown to be felicitous under the above conditions in the epidemic.

RationalLung cancer is the most common tumor worldwide, with the highest mortality rate and second highest incidence. Immunotherapy is one of the most important treatments for lung adenocarcinoma (LUAD); however, it has relatively low response rate and high incidence of adverse events. Herein, we explored the therapeutic potential of fibrinogen-like protein 1 (FGL1) for LUAD.MethodsData from GEPIA and ACLBI databases were assessed to explore gene–gene correlations and tumor immune infiltration patterns. A total of 200 patients with LUAD were recruited. FGL1 levels in the serum and cellular supernatant were determined by enzyme-linked immunosorbent assay. In vitro and in vivo experiments were performed to assess the effect FGL1 on the proliferation of LUAD cells. Cocultures were performed to explore the effect of FGL1 knockdown in lung cancer cells on T cells, concerning cytokine secretion and viability. PROMO and hTFtarget databases were used for transcription factor prediction. Quantitative polymerase chain reaction (qPCR), chromatin immunoprecipitation, and dual luciferase reporter assays were performed to validate the identified transcription factor of FGL1. Immunoprecipitation, mass spectrometry and gene ontology analysis were performed to explore the downstream partners of FGL1.ResultsFGL1 expression in LUAD was positively associated with PDL1, but not for PD1 expression. Moreover, FGL1 was positively associated with the CD3D expression and negatively associated with FOXP3, S100A9, and TPSB2 within the tumor site. FGL1 promotes the secretion of interleukin-2 by T cells in vitro, simultaneously inducing their apoptosis. Indeed, YY1 is the upstream molecule of FGL1 was found to be transcriptionally regulated by YY1 and to directly by to MYH9 to promote the proliferation of LUAD cells in vitro and in vivo.ConclusionsFGL1 is involved in the immunological and proliferative regulation of LUAD cells by controlling the secretion of important immune-related cytokines via the YY1–FGL1–MYH9 axis. Hence, targeting FGL1 in LUAD may pave the way for the development of new immunotherapies for tackling this malignancy.

Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09–3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19–7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65–2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable.

HLA-B*51:01:83 differs from HLA-B*51:01:01:01 by one single nucleotide substitutions in exon 5.

Cyclophilin A (CypA), secreted from vascular smooth muscle cells and inflammatory cells in response to oxidative stress, promotes vascular atherosclerosis and development of carotid stenosis. Increased concentration of plasma CypA in acute cerebral infarction was demonstrated clinically. The primary aim of this study was to investigate the prognostic impact between CypA level and outcome in patients with acute ischemic stroke. Admission serum CypA concentrations were detected in 66 acute cerebral infarction patients and in 52 healthy individuals. Inflammatory biomarkers, including high‐sensitivity C‐reactive protein, adhesion molecules, interleukins, and matrix‐metalloproteases, were also assessed. We also examined the relationship between plasma biomarkers, blood pressure (BP), pulse pressure, the carotid artery velocity, the prognostic assessment with modified Rankin scale, and stroke recurrence. Plasma CypA concentration was higher on the first day of hospitalization in the high BP stroke group than in normal BP stroke group, which was statistically significant, which was observed even in the third month and sixth month follow‐up outpatient periods. For stroke recurrence prediction, there was an important association between the higher (>60) pulse pressure on the seventh day of hospitalization and CypA level on the third month and sixth month follow‐up outpatient periods. Our study revealed higher circulating serum levels of CypA in the hypertensive stroke group than in the non‐hypertensive stroke group. We expect that elevated plasma CypA level and raised pulse pressure during hospitalization to become valuable biomarkers in predicting stroke recurrence in the sixth month assessment of acute cerebral infarction.

Objective Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral permeability (Ktrans) in the progression of diabetes-related CSVD. Methods Cerebral vascular permeability was crossectional measured in diabetic patients with or without CSVD, and non-diabetic patients with or without CSVD by using dynamic contrast-enhanced MRI (DCE-MRI). Results In all diabetic patients, the Ktrans of white matter (WM) was increased. However, the Ktrans of gray matter (GM) was only increased in those with CSVD. This suggested the earlier involvement of WM than GM and indicated the development of diabetes-related cerebral microangiopathy was prior to it could be visualized as features of CSVD on MRI. To broaden the application of cerebral permeability and overcome the limitations of DCE-MRI, the commonly available CSVD items of MRI were used to indicate the increase in Ktrans. Among all CSVD items, the presence of microbleeds was most correlated with the increased permeability in all patients. In contrast to non-diabetic patients, increased Ktrans in diabetes was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions This study highlights the early development of cerebral microangiopathy in diabetes and broadens the applicability of cerebral permeability. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

A high plasma concentration of proprotein convertase subtilisin/kexin type 9 is characteristic of a prothrombotic state in cardiovascular diseases. Elevated inflammatory markers, such as interleukin-6, are associated with worse outcomes after ischemic stroke. We aimed to study the role of plasma PCSK9 and IL-6 in acute ischemic stroke with dyslipidemia.We divided 123 enrolled patients with first-ever acute ischemic stroke into normotensive and high blood pressure groups and further into high and low pulse pressure subgroups. Clinical characteristics and inflammatory and metabolic parameters, including plasma PCSK9 and IL-6, were recorded.After the analysis of the normotensive and BP groups, there were positive correlations between PP and carotid stenosis (P = 0.031) and plaque numbers (P = 0.013) and between National Institute of Health Stroke Scale scores (P = 0.019) and carotid stenosis severity (P = 0.021) and resistance index (P = 0.04). There was a significant association between plasma cholesterol and PCSK9 (P = 0.044) in the low PP subgroup and IL-6 (P = 0.042) in the high PP subgroup.Our findings indicated that plasma PCSK9 levels were associated with the low PP subgroup, while IL-6 was associated with the high PP subgroup. Dyslipidemia control is also necessary for those who had a stroke and who have high PP. Further investigation to assess the role of PCSK9 and IL-6 in patients with stroke is required for early treatment and secondary prevention.

Risk factors vary in terms of the pattern of lung cancer metastasis and specific metastatic organs. In this study, we retrospectively analyzed the clinical risk factors of tumor metastasis in lung cancer patients and used second‐generation gene sequencing to characterize relevant gene mutations. The risk factors of different metastatic sites of real‐world lung cancer were explored to find the differentially expressed genes and risk factors in different metastatic organs, which laid a foundation for further study on the metastasis patterns and mechanisms of lung cancer. The clinical risk factors of tumor metastasis in 137 lung cancer patients who attended our department from May 2017 to March 2019 were retrospectively analyzed and grouped based on bone metastasis, brain metastasis, other distant metastasis, and no metastasis. Single‐ or multi‐factor logistic regression analysis was performed to analyze the effect of neutrophil/lymphocyte ratio/platelet/lymphocyte ratio/lymphocyte to monocyte ratio on platelets (PLTs) and bone metastasis by combining PLT values, age, pathology type, gender, and smoking history. Based on the presence or absence of bone metastasis, distal metastasis, and PLT values of lung cancer, 39 tissue specimens of primary lung cancer were taken for 773 gene grouping and gene mutation characterization. The tumor mutation load, gene copy number instability, microsatellite instability, and tumor heterogeneity among different groups were analyzed. Age and PLT level were independent risk factors for bone metastasis and distal metastasis, but not for brain metastasis. The RB1 gene was mutated during bone metastasis, and tumor heterogeneity was less in the elevated PLT group. PLT values were an independent risk factor for distant metastases from lung cancer other than the brain. Age has a significant effect on bone metastasis formation. RB1 gene mutation was significantly associated with bone metastasis., Age and platelet level were independent risk factors for bone metastasis and distal bone metastasis, but age and platelet level were not risk factors for brain metastasis. The RB1 gene was mutated during bone metastasis, and tumor heterogeneity was less in the elevated platelet group. Platelet values are an independent risk factor for distant metastases from lung cancer other than the brain. Age has a significant effect on bone metastasis formation. Mutations in the RB1 gene are significantly associated with bone metastasis.

Siping Zhu,1,* Wei Lin,1,* Shu Chen,1,* Hanmei Qi,1 Siting Wang,2 Aisen Zhang,1 Jinmei Cai,1 Bing Lai,1 Yunlu Sheng,1 Guoxian Ding11Division of Geriatric Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Intensive Care Unit, Nanjing Jiangning Hospital, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workBackground: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear.Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia.Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB).Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men.Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.Keywords: B-mode ultrasound, muscle thickness, pennation angle, muscle mass, muscle strength, physical performance

The incidence of deep fungal infection due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata is an opportunistic pathogen of low virulence which mainly invades the gastrointestinal, genitourinary, and respiratory tracts, but has rarely been reported as complication of articular surgery in the literature. We present a case of knee fungal arthritis caused by C. glabrata after a minimally invasive arthroscopic surgery. In this case, the patient's knee got infected after arthroscopic treatment for a recurrent popliteal cyst, and she was unable to be cured by either debridement or antifungal drugs. Mycological and molecular identification of the necrotic tissues isolate revealed C. glabrata as etiologic agent. We originally planned to conduct a debridement once again, but it was found that the articular cartilage was extensively damaged during the operation. Besides, the magnetic resonance imaging of the affected knee also showed that the infection had invaded the subchondral bone. So we treated this case with a two-stage primary total knee arthroplasty with an antibiotic-laden cement spacer block. After a 10-month follow-up, the patient had completely recovered and has not experienced any recurrence to date. In addition, we review 21 cases of C. glabrata-induced infectious arthritis described to date in the literature.

Background Variations in body temperature are highly informative during an illness. To date, there are not many adequate studies that have investigated the feasibility of a wearable wrist device for the continuous monitoring of body surface temperatures in humans. Objective The objective of this study was to validate the performance of HEARThermo, an innovative wearable device, which was developed to continuously monitor the body surface temperature in humans. Methods We implemented a multi-method research design in this study, which included 2 validation studies—one in the laboratory and one with human subjects. In validation study I, we evaluated the test-retest reliability of HEARThermo in the laboratory to measure the temperature and to correct the values recorded by each HEARThermo by using linear regression models. We conducted validation study II on human subjects who wore HEARThermo for the measurement of their body surface temperatures. Additionally, we compared the HEARThermo temperature recordings with those recorded by the infrared skin thermometer simultaneously. We used intraclass correlation coefficients (ICCs) and Bland-Altman plots to analyze the criterion validity and agreement between the 2 measurement tools. Results A total of 66 participants (age range, 10-77 years) were recruited, and 152,881 completed data were analyzed in this study. The 2 validation studies in the laboratory and on human skin indicated that HEARThermo showed a good test-retest reliability (ICC 0.96-0.98) and adequate criterion validity with the infrared skin thermometer at room temperatures of 20°C-27.9°C (ICC 0.72, P Conclusions The findings of our study show the validation of HEARThermo for the continuous monitoring of body surface temperatures in humans.

Background Alternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer. Aim To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD. Methods Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD. Results An eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways. Conclusion This study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.

Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1&ndash, 5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio: 9.91, 95% confidence interval: 4.11&ndash, 23.88). The chances of failure were inversely related to the HR increase percentage (p for trend &lt, 0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.

Rationale: The diagnosis of anaplastic lymphoma kinase (ALK)-negative inflammatory myofibroblastic tumors (IMT) remains challenging because of their morphological resemblance with spindle cell sarcoma with myofibroblastic characteristics. Patient concerns: A 69-year-old female patient presented with loco-regional recurrent IMT several times within 8 years after primary treatment and neck lymph node metastasis 3.5 years after last recurrence. Diagnosis: The primary, recurrence, and lymph node metastasis lesions were diagnosed as ALK-negative IMTs based on the histopathological features. Interventions: Biopsy samples were obtained during repeated surgeries and evaluated for genomic alterations during first and recurrent presentations. The evaluation was done using pathway-driven massive parallel sequencing, and genomic alterations between primary and recurrent tumors were compared. Outcomes: Copy number gains and overexpression of mouse double minute 2 homolog (MDM2) and cyclin dependent kinase 4 (CDK4) were observed in the primary lesion, and additional gene amplification of Discoidin Domain Receptor Tyrosine Kinase 2 (DDR2), Succinate Dehydrogenase Complex II subunit C (SDHC), and thyroid stimulating hormone receptor (TSHR) Q720H were found in the recurrent tumors. Metastases to the neck lymph node were observed 3.5 years after recurrence. Lessons: Our results indicated genetic evolution in a microscopically benign condition and highlighted the importance of molecular characterization of fibro-inflammatory lesions of uncertain malignant potential.

Background Development assistance for health (DAH) is an important component of foreign assistance. International health consultants usually play a key role in the international DAH field. However, there is still a shortage of consulting training in China. To address this issue and develop new backup force of DAH for China, the Global Health Institute of Wuhan University (GHIWHU) launched a training program called the “Consulting Training Course for International Development Assistance for Health”. The purpose of this article is to evaluate the impact of the training on participants. Methods We conducted the analysis using Kirkpatrick’s model. An evaluation survey examining participants’ reaction (level 1) and learning (level 2) was carried out among trainees following the training, and a follow-up telephone interview of application (level 3) was made in three months after the training. Results A total of 25 participants from Chinese Consortium of Universities for Global Health (CCUGH) attended the training program. Results of satisfaction evaluation indicated that the training program was well received, with more than 85% of participants felt satisfied or relatively satisfied with the training. Trainees’ self-ratings of the consulting knowledge and skills showed a significant increase (p

Background Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015. Methods A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups. Results There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/μl vs. 91 x103/μl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001). Conclusions AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality., Author summary Dengue fever (DF) is currently one of the most severe public health problems. Clinical presentations of dengue are diverse and non-specific, often with unpredictable clinical progression and outcome. Hepatic dysfunction and abnormal coagulation factors are common in acute dengue illness, reflected by abnormal alanine aminotransferase (AST), aspartate aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts. However, there is no information available about the monitoring frequency required, which could help identify those dengue patients who are likely to die, especially during epidemic outbreaks with limited healthcare resources. We examined all the laboratory-confirmed dengue patients who admitted to the major tertiary hospital in Tainan during the 2015 dengue outbreak, and the different trajectories of hepatic function and coagulation factors between survivors and rapidly fatal dengue patients were analyzed. Although there were no differences in AST, ALT, aPTT, and platelet counts between the survivor and fatal groups on the day DF symptoms first appeared, the differences increased from the early stages of infection and became more prominent during the early stages of the illness. The necessity of monitoring the AST, ALT, aPTT, and platelet count frequently during the febrile phase is emphasized by this study.

BACKGROUND Cyclophilin A plays a pathogenic role in the development and progression of atherosclerosis, which can be assessed by measuring carotid intima-media thickness. The primary aim of this study was to examine the interaction between plasma Cyclophilin A level and carotid intima-media thickness in patients with acute ischemic stroke. METHOD Plasma concentration of Cyclophilin A was measured on admission in 66 consecutive patients who had been hospitalized for acute cerebral stroke and in 52 case-control subjects without a history of acute stroke. Subjects in both groups also underwent ultrasound B-mode imaging to measure the mean and maximum intima-media thickness of the carotid artery. Inflammatory biomarkers including high-sensitivity C-reactive protein and fibrinogen were also assessed. RESULTS We found that the plasma concentration of Cyclophilin A was significantly higher in patients with acute ischemic stroke (p = 0.042). Increased Cyclophilin A was also correlated with carotid intima-media thickness in the patient group (p < 0.001). Among the risk factors for cerebral stroke examined in this study, only hypertension was significantly associated with plasma Cyclophilin A level. CONCLUSION Increased plasma Cyclophilin A levels might be involved in the pathophysiology of acute ischemic stroke and Cyclophilin A might serve as a biomarker in risk assessment of acute stroke patients.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Background Little is known about the effects of Kinesio taping and therapeutic exercise on correcting forward head posture. Objective To compare Kinesio taping versus therapeutic exercise for forward head posture on static posture, dynamic mobility and functional outcomes. Methods Sixty subjects (31 women, 29 men) with forward head postures participated in this study. They were randomly assigned to either one of the three groups: (1) exercise group (n = 20), (2) taping group (n = 20), and (3) control groups (n = 20). The horizontal forward displacement (HFD) between ear lobe and acromion process, upper cervical and lower cervical angle (UCA, LCA), active range of motion (AROM) of cervical spine, and neck disability index (NDI) were measured before and after a 5-week intervention, and a 2-week follow-up. Data were analyzed by means of a mixed design repeated-measures ANOVA. Results Both taping and exercise groups showed significant improvements in HFD compared with the control group at post-treatment and follow-up. Compared with the control group, the exercise group exhibited significant improvements in the LCA and the side bending AROM at post-treatment. Conclusions Both Kinesio taping and therapeutic exercise improve forward head posture after intervention and a 2-week follow-up. The effectiveness of therapeutic exercise is better than taping.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

BACKGROUND Rotator cuff injury is the most common cause of shoulder disability, and although the repair technique has improved, the rate of rotator cuff reduction after repair is still high. The fibrocartilage region, which appears to be histologically inserted, cannot be regenerated. In recent years, studies have reported that mesenchymal stem cells (MSCs) have enhanced cartilage regeneration in the tendon and bone interface after rotator cuff repair, which has become a hot topic of research. MATERIAL AND METHODS Two mesenchymal stem cell types, SMSC (synovial-derived mesenchymal stem cells) and BMSC (bone marrow-derived mesenchymal stem cells) were intervened using kartogenin (KGN). The cytotoxicity was evaluated and the proliferation of the 2 cells was observed. Four commonly used cartilage phenotype genes were detected by quantitative real-time polymerase chain reaction, and the cartilage differentiation of MSCs induced by KGN was explored. The bidirectional regulation of the expression of BMP-7 and the downstream gene Smad5 was observed by constructing a lentiviral overexpression vector containing the target gene BMP-7. To explore whether BMP-7/Smad5 pathway activation promotes differentiation of SMSCs into chondrocytes. RESULTS KGN can induce the selective differentiation of endogenous MSCs into chondrocytes by activating the BMP-7/Smad5 pathway, which promotes the regeneration of interfacial cartilage, and improves the quality of tendon healing of the tendon after rotator cuff repair. CONCLUSIONS This study found a new biological intervention method to promote the effect of tendon on bone healing after rotator cuff repair.

Transcatheter pulmonary valve replacement (TPVR) is a new, less invasive alternative to surgical valve replacement for residual pulmonary regurgitation (PR) after initial repair of tetralogy of Fallot (TOF) [(1,2)][1]. We report the first-in-man implantations of a novel transcatheter pulmonary valve

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations. Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing). Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ± 0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ± 0.53 ng/mL) than those with wild-type carrier (0.74 ± 0.40 ng/mL) when they have repaired renal function. Heart failure patients with severe renal dysfunction (GFRC mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.

Tyrosinase is a key enzyme during the production of melanins in plants and animals. A class of novel N-aryl-N'-substituted phenylthiourea derivatives (3a-i, 6a-k) were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed some 4,5,6,7-tetrahydro-2-[[(phenylamino)thioxomethyl]amino]-benzo[b]thiophene-3-carboxylic acid derivatives (3a-i) exhibited moderate inhibitory potency on diphenolase activity of tyrosinase. When the scaffold of 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid was replaced with 2-(1,3,4-thiadiazol-2-yl)thio acetic acid, the inhibitory activity of compounds (6a-k) against tyrosinase was improved obviously; especially, the inhibitory activity of compound 6h (IC50=6.13 μM) is significantly higher than kojic acid (IC50=33.3 μM). Moreover, the analysis on inhibition mechanism revealed that compound 6h might plays the role as a noncompetitive inhibitor.

SummaryObjectives: To find discriminative combination of influential factors of Intracerebral hematoma (ICH) to cluster ICH patients with similar features to explore relationship among influential factors and 30-day mortality of ICH. Methods: The data of ICH patients are collected. We use a decision tree to find discriminative combination of the influential factors. We cluster ICH patients with similar features using Fuzzy C-means algorithm (FCM) to construct a support vector machine (SVM) for each cluster to build a multi-SVM classifier. Finally, we designate each testing data into its appropriate cluster and apply the corresponding SVM classifier of the cluster to explore the relationship among impact factors and 30-day mortality. Results: The two influential factors chosen to split the decision tree are Glasgow coma scale (GCS) score and Hematoma size. FCM algorithm finds three centroids, one for high danger group, one for middle danger group, and the other for low danger group. The proposed approach outperforms benchmark experiments without FCM algorithm to cluster training data. Conclusions: It is appropriate to construct a classifier for each cluster with similar features. The combination of factors with significant discrimination as input variables should outperform that with only single discriminative factor as input variable.

Objective This study aimed to investigate the influence of injection rates of calibrating standard solution on monitoring pulse indicator continuous cardiac output (PICCO, made in Germany), and thereby to provide significant references for clinical practice. Methods A total of 108 critical patients in stroke intensive care unit were identified. All these participants received transesophageal cardiac color Doppler ultrasound, and within 15 min PICCO equipment was utilized to monitor the relevant parameters, by means of 0 °C calibrating standard solution, and the injection speeds were 2–4, 5–7, and 8–10 s. Besides, the monitoring indicators were as follows, cardiac index, global ejection fraction, global end diastolic volume index. The potential correlations were evaluated between PICCO and transesophageal cardiac color Doppler ultrasound. Results All the data was available, and the monitored parameters of PICOO at 2–4, 5–7, and 8–10 s were positively correlated with the parameters obtained from transesophageal cardiac color Doppler ultrasound (P

Background Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses. Methods A descriptive study was conducted using secondary data from the Dengue Disease Reporting System in Tainan, Taiwan, between January 1 and December 31, 2015. A multivariate stepwise logistic regression was used to identify the risk factors for the adverse prognoses: ICU admissions and mortality. Results There were 22,777 laboratory-confirmed reported cases (mean age 45.6 ± 21.2 years), of which 3.7% were admitted to intensive care units (ICU), and 0.8% were fatal. The most common symptoms were fever (92.8%), myalgia (26.6%), and headache (22.4%). The prevalence of respiratory distress, altered consciousness, shock, bleeding, and thrombocytopenia increased with age. The multivariate analysis indicated that being in 65–89 years old age group [Adjusted Odds Ratio (aOR):4.95], or the 90 years old and above age group (aOR: 9.06), and presenting with shock (aOR: 8.90) and respiratory distress (aOR: 5.31) were significantly associated with the risk of ICU admission. While old age (aOR: 1.11), respiratory distress (aOR: 9.66), altered consciousness (aOR: 7.06), and thrombocytopenia (aOR: 2.55) were significantly associated with the risk of mortality. Conclusions Dengue patients older than 65 and those with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality. First-line healthcare providers need to be aware of the varied presentations between the different age groups to allow early diagnosis and in-time management, which would prevent ICU admissions and fatalities in dengue patients., Author summary Clinical presentations of dengue fever (DF) are diverse and non-specific and often have unpredictable progression and outcomes. The patients in the 2015 dengue epidemics in Taiwan were predominantly much older than in other countries in Southeast Asia. However, limited data are available in Taiwan on dengue patients with adverse prognoses who were admitted to ICU or on those with fatal complications. All suspected dengue cases were reported to the Dengue Disease Reporting System in Taiwan. We examined patients who had laboratory-confirmed dengue in Tainan during the 2015 dengue outbreak and analyzed secondary data from the reporting system. Of these patients, 3.7% were admitted to ICU, and 0.8% died. Patients who received adverse prognoses were generally of older age, had a critical presentation at the time of reporting, and experienced a rapid progress of the disease, highlighting that people with severe and non-specific signs and symptoms at the time of reporting were at a higher risk of ICU admission and mortality.

Supplemental Digital Content is available in the text, Background: A pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) is a strong indicator of the benefit of therapy and presents an early surrogate for a favorable long-term outcome. It remains unclear whether Ki-67, a marker for tumor proliferation, can function as a predictor of the response to NCT in breast cancer. The objective of this meta-analysis was to compare the pCR rate and clinical outcomes in breast cancer patients with different Ki-67 labeling indexes (Ki-67 LI) who received NCT. Methods: Clinical studies were retrieved from the electronic databases of PubMed, Embase, Clinical Trials, Wanfang, and the Chinese National Knowledge Infrastructure, from their inception to July 31, 2017. Meta-analysis was performed on pool eligible studies to determine whether Ki-67 LI was associated with the pCR rate and clinical outcomes of breast cancer patients who were treated with NCT. Pooled analyses were performed using fixed effects models. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 36 studies involving 6793 patients were included in the meta-analysis. Pooled analysis results revealed that patients with high Ki-67 LI exhibited significantly higher pCR rates (odds ratio [OR] = 3.94, 95% confidence interval [CI]: 3.33–4.67, P

Ultrasound Nakagami imaging has recently attracted interest as an imaging technique for analyzing envelope statistics. Because the presence of structures has a strong effect on estimation of the Nakagami parameter, previous studies have indicated that Nakagami imaging should be used specifically for characterization of soft tissues with fewer structures, such as liver tissues. Typically, changes in the properties of the liver parenchyma cause the backscattered statistics to transform from a Rayleigh distribution to a pre-Rayleigh distribution, and this transformation can be visualized using a Nakagami imaging technique. However, different estimators result in different estimated values; thus, the performance of a Nakagami image may depend on the type of estimator used. This study explored the effects of various estimators on ultrasound Nakagami imaging to describe the backscattered statistics as they change from a Rayleigh distribution to a pre-Rayleigh distribution. Simulations and clinical measurements involving patients with liver fibrosis (n = 85) yielded image data that were used to construct B-mode and conventional Nakagami images based on the moment estimator (denoted as mINV images) and maximum-likelihood estimator (denoted as mML images). In addition, novel window-modulated compounding Nakagami images based on the moment estimator (denoted as mWMC images) were also obtained. The means and standard deviations of the Nakagami parameters were examined as a function of the backscattered statistics. The experimental results indicate that the mINV, mML and mWMC images enabled quantitative visualization of the change in backscattered statistics from a Rayleigh distribution to a pre-Rayleigh distribution. Importantly, the mWMC image is superior to both mINV and mML images because it simultaneously realizes sensitive detection of the backscattered statistics and a reduction of estimation variance for image smoothness improvement. We therefore recommend using mWMC image as a novel strategy in Nakagami imaging technique for liver tissue characterization.

Background The association of schizophrenia with peptic ulcer is not conclusive. In the last 30 years, there has been little evaluation of peptic ulcer among schizophrenia patients. Methods To explore the relation of peptic ulcer and schizophrenia during this new phase, we used the data from Taiwan insurance claims, identified 1496 schizophrenia patients (ICD-9-CM: 295) and selected 5984 non-schizophrenia controls that were frequency-matched by sex, age, and index year with schizophrenia patients during the years 1998–2001. All subjects were free of peptic ulcer at baseline. We measured incidences of peptic ulcer (ICD-9-CM: 531–534) until the end of 2009. Results The incidence of peptic ulcer was 1.27 times higher in schizophrenia patients than in the control group (12.1vs. 9.52 per 1000 person-years). Patients are at higher risk taking anti-depression, anxiolytic and hypnotics or non-steroidal anti-inflammatory drugs. After controlling the confounding factors, schizophrenia patients had no significant increase incidence of peptic ulcer. Conclusion Schizophrenia patients have a slightly higher risk of peptic ulcer compared to the general population. This might be due to a higher rate of taking anti-depression, anxiolytic and hypnotics or non-steroidal anti-inflammatory drugs and alcoholism among this group.