Myositis Autoantibody Profiles and Clinical Significance in Patients with Inflammatory Myopathies in Southwest China.

BACKGROUND: The purpose of this study is to analyze the distribution of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients with idiopathic inflammatory myopathies (IIMs) in southwest China and to explore the relevance between each subtype, each clinical feature, and to explore the relevance between the laboratory indexes. METHODS: For this study, 200 patients with IIMs were tested for myositis autoantibodies. Clinical manifestations and laboratory metrics were collected and the correlations between autoantibodies and clinical phenotypes were analyzed. RESULTS: MSAs were found in 73.5% of the patients. The most frequently MSAs were anti-MDA5 (26.8%), followed by anti-ARS (18.5%). Anti-Ro52 was the most prevalent in MAAs (46.2%). Interstitial lung disease (ILD) and arthralgia were more frequent in anti-MDA5 and anti-Jo-1 positive groups (each p < 0.05). Anti-TIF1-γ and anti-NXP2 were associated with dysphagia (each p < 0.05). Different antibody subtypes were associated with laboratory indicators of response to muscle damage and immune status. Logistic regression showed that anti-MDA5 and anti-Jo-1 were independent risk factors for ILD (OR = 4.542, p = 0.004; OR = 4.290, p = 0.018, respectively) and arthralgia (OR = 7.856, p = 0.000; OR = 5.731, p = 0.004, respectively), whereas anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia (OR = 4.521, p = 0.009; OR = 6.889, p = 0.017, respectively). CONCLUSIONS: Different antibody subtypes were associated with specific clinical features. Anti-MDA5 and anti-Jo-1 were independent risk factors for ILD and arthralgia. Anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia.

NLRC5 promotes endometrial carcinoma progression by regulating NF-κB pathway-mediated mismatch repair gene deficiency.

The innate immune molecule NLR family CARD domain-containing 5 (NLRC5) plays a significant role in endometrial carcinoma (EC) immunosurveillance. However, NLRC5 also plays a protumor role in EC cells. Mismatch repair gene deficiency (dMMR) can enable tumors to grow faster and also can exhibit high sensitivity to immune checkpoint inhibitors. In this study, we attempted to determine whether NLRC5-mediated protumor role in EC is via the regulation of dMMR. Our findings revealed that NLRC5 promoted the proliferation, migration, and invasion abilities of EC cells and induced the dMMR status of EC in vivo and in vitro. Furthermore, the mechanism underlying NLRC5 regulated dMMR was also verified. We first found NLRC5 could suppress nuclear factor-kappaB (NF-κB) pathway in EC cells. Then we validated that the positive effect of NLRC5 in dMMR was restricted when NF-κB was activated by lipopolysaccharides in NLRC5-overexpression EC cell lines. In conclusion, our present study confirmed the novel NLRC5/NF-κB/MMR regulatory mechanism of the protumor effect of NLRC5 on EC cells, thereby suggesting that the NLRC5-mediated protumor in EC was depend on the function of MMR.

Digital PCR to Measure SARS-CoV-2 RNA, Variants, and Outcomes in Youth.

BACKGROUND: The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St. Jude Children's Research Hospital between March 28, 2020, and January 31, 2022. METHODS: Demographic and clinical information from children, adolescents, and young adults treated at St. Jude Children's Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus. RESULTS: Four hundred and sixty-two patients aged 0-24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%), and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/mL, and higher viral RNA loads were associated with symptoms (OR 1.32; CI 95% 1.16-1.49) and respiratory disease (OR 1.23; CI 95% 1.07-1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis. CONCLUSIONS: SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, and comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment.

The clinical value of the monocyte to high-density lipoprotein cholesterol ratio and alkaline phosphatase-to-platelet ratio in primary biliary cholangitis.

This study aimed to evaluate the clinical value of the monocyte to high-density lipoprotein cholesterol ratio (MHR) and alkaline phosphatase-to-platelet ratio (APPR) in the diagnosis and prognosis of primary biliary cholangitis (PBC). Clinical and laboratory data were retrospectively collected and analyzed from 92 PBC patients, 92 patients with autoimmune hepatitis (AIH), 120 patients with chronic hepatitis B (CHB) and 124 healthy controls (HCs). We compared the levels of MHR and APPR among the groups with PBC, AIH, CHB and HCs, and analyzed the correlations between MHR and APPR with laboratory indices including aspartate aminotransferase platelet ratio index, fibrosis index based on 4 factors, and Mayo score in PBC. Receiver operating characteristic curves were used to analyze the diagnostic performance of MHR and APPR for PBC, AIH, and CHB, respectively. MHR and APPR were significantly increased in PBC group than that in AIH, CHB and HCs groups (each P < .05). MHR and APPR were significantly higher in Child class B|C than that in class A in PBC patients. (P < .01, P < .05, respectively). MHR and APPR were positively related to the Mayo score [R = 0.508 (P < .001), R = 0.295 (P = .008), respectively]. The area under the receiver operating characteristic curves of MHR and APPR in diagnosing PBC were 0.764 (95% confidence interval [CI]: 0.699-0.821, P < .001) and 0.952 (95% CI: 0.915-0.977, P < .001), respectively, and the area under the curve of the combination of both was 0.974 (95% CI: 0.941-0.991, P < .001). MHR and APPR may prove to be useful prognostic biomarkers for PBC, and the combination of MHR and APPR have some clinical diagnostic value of PBC.

NLRC5 potentiates anti-tumor CD8+ T cells responses by activating interferon-ß in endometrial cancer.

OBJECTIVES: NLR family CARD domain containing 5 (NLRC5) could promote major histocompatibility complex class I (MHC-I)-dependent CD8+ T cell-mediated anticancer immunity. In this study, the immunosurveillance role and underlying mechanisms of NLRC5 in endometrial cancer (EC) were characterized. METHODS: CD8+ T cells were separated from healthy women's peripheral blood by using magnetic beads. The effect of NLRC5 and interferon-ß (IFN-ß) on immunosurveillance of EC were examined through a mouse tumor model and a CD8+ T cell-EC cell coculture system after NLRC5 overexpression and IFN-ß overexpression or depletion. The effect of NLRC5 on IFN-ß expression was examined with gain- and loss-of-function experiments. RESULTS: NLRC5 overexpression in the EC cell and CD8+ T cell coculture system inhibited EC cell proliferation and migration and promoted EC cell apoptosis and CD8+ T cell proliferation. In vivo, NLRC5 overexpression increased the proportion of CD8+ T cells and inhibited EC progression. Furthermore, IFN-ß overexpression in the EC cell and CD8+ T cell coculture system activated CD8+ T cell proliferation; however, genetic depletion of IFN-ß exerted the opposite effects. In addition, NLRC5 could negatively regulate IFN-ß expression in EC cells. Mechanistically, NLRC5 potentiated the antitumor responses of CD8+ T cells to EC by activating IFN-ß. CONCLUSIONS: Taken together, our findings demonstrated that NLRC5 potentiates anti-tumor CD8+ T cells responses by activating interferon-ß in EC, suggesting that genetically escalated NLRC5 and IFN-ß may act as potential candidates for the clinical translation of adjuvant immunotherapies to patients with EC.

Prediction of Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Quantitative Digital Polymerase Chain Reaction Normalized to International Units.

Although numerous studies have evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using cycle threshold (Ct) values as a surrogate of viral ribonucleic acid (RNA) load, few studies have used standardized, quantitative methods. We validated a quantitative SARS-CoV-2 digital polymerase chain reaction assay normalized to World Health Organization International Units and correlated viral RNA load with symptoms and disease severity.

Clinical significance of serum ferritin in patients with systemic sclerosis.

OBJECTIVE: The purpose of this study was to explore the clinical significance of serum ferritin (SF) in patients with systemic sclerosis (SSc). METHODS: The levels of SF were measured in 115 patients with SSc and 117 healthy controls (HCs). Clinical characteristics and laboratory indexes between the high ferritin SSc group and the normal ferritin SSc group were analyzed. RESULTS: The level of SF in SSc patients was significantly higher than that in HCs (319.78 [179, 554.33] ng/ml vs. 99 [49.03, 164.29] ng/ml, p < 0.01). Compared with the normal ferritin SSc group, the high ferritin SSc group was more likely to develop skin diffuse cutaneous SSc, fingertip arthralgia, and cardiac involvement. In addition, the levels of glutamine transaminase (GGT), alanine aminotransferase (ALT), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LD), immunoglobulin G (IgG), immunoglobulin A (IgA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the positive rate of anti-Scl70 antibody in the high ferritin SSc group were significantly higher (each p < 0.05). SF was positively correlated with GGT, ALT, CK, CK-MB, LD, IgA, CRP, and ESR (each p < 0.05). Multiple linear regression analysis showed that cardiac involvement, ALT, and ESR were independent influencing factors of SF in SSc. CONCLUSION: Our study shows that the level of SF in patients with SSc is increased, and the elevated SF is related to abnormal liver function, myocardial involvement, inflammatory status, and production of autoantibodies in SSc. Cardiac involvement, ALT, and ESR are independent factors affecting SF in SSc.

A case of CIC-rearranged sarcoma with CIC-LEUTX gene fusion in spinal cord.

A 16-year-old male was admitted to the hospital for weakness of both lower extremities. Magnetic resonance imaging revealed an intraspinal extramedullary subdural mass at the thoracic 9 level. Microscopically, the tumor cells were small to medium sized and round to ovoid in shape. They were distributed in diffuse sheets or showed nodular appearance. The nucleus of the tumor had mild-to-moderate atypia, with vesicular chromatin and prominent nucleoli. A smaller proportion of tumor cells demonstrated rhabdoid morphology. Focal myxoid stromal change was present, in which tumor cells exhibited spindle shapes. Approximately two mitoses were counted per 10 high-power fields. No necrosis was observed. The tumor cells were focal positive for CD99; multifocal positive for WT1; diffuse positive for nestin, synaptophysin, and D2-40; partial positive for GFAP; focal positive for desmin and SSTR2; and scattered positive for S-100 protein. The Ki-67 labeling index was approximately 20%. Genetic testing revealed CIC-LEUTX gene fusion. Considering the patient's history, clinical data, pathological findings and genetic findings, we rendered a rare tumor named CIC-rearranged sarcoma with CIC-LEUTX gene fusion.

Epidemiology and risk factors for diabetes in the suburbs of Beijing: a retrospective cohort study.

OBJECTIVE: We aimed to detect the incidence and risk factors of type 2 diabetes mellitus (T2DM) development in the suburbs of Beijing. DESIGN: Cohort study with record linkage to incidence data. SETTING: We performed a 5-year follow-up study in a randomly selected suburban population including 1114 subjects aged ≥18 years living in the suburbs of Beijing. PARTICIPANTS: 118 subjects with T2DM at baseline according to the 1999 WHO criteria were excluded, and 895 subjects attended the follow-up assessment in 2012. The non-diabetic subjects at baseline were classified into two groups: normal glucose tolerance (NGT) group (n=673) and impaired glucose regulation (IGR) group(n=222).The incidence and risk factors of diabetes development in each group were investigated. OUTCOME MEASURES: A structured questionnaire about sociodemographic characteristics, height, weight, waist circumference, hip circumference, blood pressure, oral glucose tolerance test and serum lipid levels. RESULTS: Out of the 895 non-diabetic subjects, 67 developed diabetes with 29 in the NGT group and 38 in the IGR group, respectively, after a 5-year follow-up, producing an overall 5-year cumulative incidence of diabetes of 13%. The incidence of diabetes was 15.5 cases per 1000 person-years, 8.9 cases per 1000 person-years in the NGT group and 35.7 cases per 1000 person-years in the IGR group (p<0.01; RR 4.03; 95% CI 2.58 to 9.29). Binary logistic regression analysis showed that the risk factors for diabetes development included fasting plasma glucose (FPG) in the NGT group, and sex, the waist-to-hip ratio, FPG and diastolic blood pressure (DBP) in the IGR group. CONCLUSIONS: During a mean follow-up of 5.0 years, the incidence of T2DM in the suburbs of Beijing was 15.5 per 1000 person-years. Early prevention of diabetes should focus on IGR subjects. Elevated FPG predicted diabetes development for both NGT and IGR subjects. Female sex, overweight/obesity and DBP are risk factors for diabetes development in IGR subjects.

H2S quartz-enhanced photoacoustic spectroscopy sensor employing a liquid-nitrogen-cooled THz quantum cascade laser operating in pulsed mode.

In this work, we report on a quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor for hydrogen sulfide (H2S) detection, exploiting a liquid-nitrogen-cooled THz quantum cascade laser (QCL) operating in pulsed mode. The spectrophone was designed to accommodate a THz QCL beam and consisted of a custom quartz tuning fork with a large prong spacing, coupled with acoustic resonator tubes. The targeted rotational transition falls at 2.87 THz (95.626 cm-1), with a line-strength of 5.53 ∙ 10-20 cm/mol. A THz QCL peak power of 150 mW was measured at a heat sink temperature of 81 K, pulse width of 1 µs and repetition rate of 15.8 kHz. A QEPAS record sensitivity for H2S detection in the THz range of 360 part-per-billion in volume was achieved at a gas pressure of 60 Torr and 10 s integration time.

Family History of Diabetes and the Effectiveness of Lifestyle Intervention on Insulin Secretion and Insulin Resistance in Chinese Individuals with Metabolic Syndrome.

AIMS: The current study aims to explore if a family history of diabetes can influence the efficiency of lifestyle intervention on insulin secretion and study the insulin resistance in Chinese men and women with metabolic syndrome in a cohort with a 2-year follow-up. METHODS: 151 individuals (90 individuals did not have a family history of diabetes (DMFH (-)) and 61 with a family history of diabetes (DMFH (+)) with metabolic syndrome participated in the lifestyle intervention program at baseline and finished with 1-year follow-up. 124 individuals have two-year follow-up data. A family history of diabetes was ascertained by self-report. Lifestyle interventions were individual sessions on lifestyle changes. RESULTS: During the 1-year follow-up, Ln Insulinogenic index (Δbaseline-1year = 0.29 ± 0.65, P = 0.001) and 30-min glucose (Δbaseline-1year = -0.41 ± 1.71, P = 0.024) changed significantly in the DMFH(-) group; in the DMFH(+) group, Ln ISIm (Δbaseline-1year = -0.22 ± 0.60, P = 0.022) and 30-min glucose (Δbaseline-1year = 0.53 ± 1.89, P = 0.032) changed significantly, and there was no significant change of other parameters. The change of 30 min glucose during a 1-year intervention has shown a significant difference between the two groups (P = 0.002). During the 2 years intervention, Ln Insulinogenic index changed significantly in the DMFH(-) group (Δbaseline-1year = 0.33 ± 0.66, P < 0.001 and Δbaseline-2year = 0.43 ± 1.17, P = 0.034). Fasting insulin (Δbaseline-2year = 2.95 ± 8.69, P = 0.034), 2 h insulin (Δbaseline-2year = 23.75 ± 44.89, P = 0.002), Ln HOMA-B (Δbaseline-2year = 0.43 ± 1.02, P = 0.009), Ln HOMA-IR (Δbaseline-2year = 0.53 ± 1.04, P = 0.002), Ln ISIm (Δbaseline-2year = 0.52 ± 0.95, P = 0.004), and Ln Insulinogenic index (Δbaseline-2year = 0.66 ± 1.18, P = 0.047) changed significantly after 2 years of intervention, compared to the baseline in the DMFH(+) group. The change of Ln ISIm (P = 0.023), fasting (P = 0.030), and 2 h insulin (P = 0.007) during the 2-year intervention has shown a significant difference between the two groups. Family history of diabetes was related with a 0.500 unit increase in 2-year ISIm (P = 0.020) modified by lifestyle intervention adjusted for age, baseline BMI, sex, and baseline waist circumference and a 0.476 unit increase in 2-year ISIm (P = 0.027) with extra adjustment for weight change. CONCLUSIONS: Patients with a family history of diabetes benefit more from lifestyle intervention in regard to insulin resistance than those without a family history of diabetes adjusting for age, baseline BMI, sex, baseline waist circumference, and weight change.

Maternal and paternal histories differentially influence risks for diabetes, insulin secretion and insulin resistance in a Chinese population.

AIMS/INTRODUCTION: To investigate the differential effects of maternal versus paternal history of diabetes on the risks for diabetes and prediabetes, as well as on insulin secretion and resistance in Chinese individuals. MATERIALS AND METHODS: From the 2007 to 2008 China National Diabetes and Metabolism Disorders Study, 39,244 participants were included and divided into four categories: negative parental history, paternal history only (PH), maternal history only (MH), and both paternal and maternal history. RESULTS: The age- and sex-standardized prevalence rates of diabetes in the negative parental history, PH, MH, and both paternal and maternal history groups were 8.59, 12.56, 15.86 and 29.81%, respectively. The prevalence rates of impaired glucose metabolism were 24.13, 25.41, 31.13 and 50.80%, with the prevalence in the MH group being significantly higher than that in the PH group. Compared with that in the FH0 group, the risks of diabetes in the PH, MH, and both paternal and maternal history groups were 2.01-, 2.67- and 6.37-fold greater, and the risks of impaired glucose metabolism were 1.28-, 1.65- and 3.45-fold greater. In addition, MH had a significantly greater impact on impaired glucose metabolism than PH (PMHvsPH  = 0.0292). Regression analyses suggested MH was associated with homeostatic model assessment for ß-cell function (ß[SE] = -0.0910[0.0334], P = 0.0065), insulinogenic index (-0.1866[0.0550], P = 0.0007), homeostatic model assessment for insulin resistance (0.0662[0.0227], P = 0.0036) and Matsuda Index [-0.0716(0.0203), P = 0.0004]. PH was specifically associated with homeostatic model assessment for insulin resistance (0.1343[0.0267], P < 0.0001) and Matsuda Index (-0.1566[0.0243], P < 0.0001), but the effects were stronger than those of MH (PMHvsPH  = 0.0431, 0.0054). CONCLUSIONS: MH and PH differentially influence the risks for diabetes, insulin secretion, and insulin resistance in the Chinese population, suggesting they participate in the pathogenesis of diabetes through different mechanisms.

Association Between Cannabinoid Receptor-1 Gene Polymorphism and the Risk of Diabetic Nephropathy Among Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The cannabinoid receptor 1 (CNR1) gene polymorphism is reportedly associated with components of metabolic syndrome and coronary artery diseases in patients with type 2 diabetes mellitus (T2DM). We investigated whether the common variant rs10493353 polymorphism is associated with diabetic nephropathy (DN) in T2DM patients. PATIENTS AND METHODS: T2DM patients with DN were enrolled as a case group, and patients with only T2DM as a control group. Demographic data and biochemical parameters were collected. The polymerase chain reaction-based restriction fragment length polymorphism technique was used for genotyping. The odds ratio and 90% confidence interval were calculated to assess the association between genotypes and the risk of DN. RESULTS: In total, 320 T2DM patients and 320 DN patients were enrolled. Compared with T2DM patients, the DN patients have a significantly larger body mass index (BMI), longer duration of disease, and higher proportions of smokers, drinkers, and hypertension. The risk of DN was significantly decreased by genotypes AA (OR=0.39, 95% CI=0.23-0.67) and GA (OR=0.53, 95% CI=0.37-0.75) vs GG (codominant model), GA/AA vs GG (OR=0.49, 95% CI=0.35-0.67; dominant model), AA vs GG/GA (OR=0.47, 95% CI=0.28-0.80; recessive model), and the A allele (OR=0.52, 95% CI=0.40-0.68; allele model). Multiple logistic regressions still show significant levels. Negative interactions were found between gene and clinical parameters, including drinking, smoking, BMI, and hypertension. CONCLUSION: The A allele of CNR1 gene rs10493353 may be a protective factor for DN in T2DM patients. The risk factors of DN can affect the protective role of A allele in the progression of DN.

Modeling and improving the output power of terahertz master-oscillator power-amplifier quantum cascade lasers.

A model based on carrier rate equations is proposed to evaluate the gain saturation and predict the dependence of the output power of a terahertz master-oscillator power-amplifier quantum cascade laser (THz-MOPA-QCL) on the material and structure parameters. The model reveals the design rules of the preamplifier and the power extractor to maximize the output power and the wall-plug efficiency. The correction of the model is verified by its agreement with the experiment results. The optimized MOPA devices exhibit single-mode emission at ∼ 2.6 THz with a side mode suppression ratio of 23 dB, a pulsed output power of 153 mW, a wall-plug efficiency of 0.22%, and a low divergence angle of ∼6°×16°, all measured at an operation temperature of 77 K. The model developed here is helpful for the design of MOPA devices and semiconductor optical amplifiers, in which the active region is based on intersubband transitions.

Genotypic and phenotypic spectra of hemojuvelin mutations in primary hemochromatosis patients: a systematic review.

Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10-2). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10-3, 1.69×10-2). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10-2). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10-2). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10-2, 3.93×10-2). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.

Terahertz master-oscillator power-amplifier quantum cascade laser with a grating coupler of extremely low reflectivity.

A terahertz master-oscillation power-amplifier quantum cascade laser (THz-MOPA-QCL) is demonstrated where a grating coupler is employed to efficiently extract the THz radiation. By maximizing the group velocity and eliminating the scattering of THz wave in the grating coupler, the residue reflectivity is reduced down to the order of 10-3. A buried DFB grating and a tapered preamplifier are proposed to improve the seed power and to reduce the gain saturation, respectively. The THz-MOPA-QCL exhibits single-mode emission, a single-lobed beam with a narrow divergence angle of 18° × 16°, and a pulsed output power of 136 mW at 20 K, which is 36 times that of a second-order DFB laser from the same material.

Which Patients Will Benefit from a Switch in Therapy from Premixed Insulin to Insulin Glargine plus Oral Antidiabetic Drugs? Further Analysis of the Lantus Registry Study.

INTRODUCTION: This subgroup analysis of data from the 16-week Lantus Registry Study in China investigated the characteristics of patients with type 2 diabetes mellitus (T2DM) associated with clinical benefits of transitioning therapy from premixed insulin to insulin glargine (100 U/ml) plus oral antidiabetic drugs (OADs). METHODS: The modified intention-to-treat population of the Lantus Registry Study, comprising 1847 patients with T2DM, were included in the current subgroup analyses. Enrolled patients were divided into subgroups based on efficacy variables of endpoint glycated hemoglobin (HbA1c), endpoint fasting plasma glucose (FPG), and change in HbA1c from baseline. The baseline characteristics of those who did and did not achieve HbA1c <7.0% were compared, as were those with improvement, no change, or deterioration in HbA1c. Characteristics of patients who were unable to achieve HbA1c <7.0%, further grouped according to whether or not they achieved FPG ≤6.1 mmol/L, were also compared. Logistic regression analysis was used to identify factors associated with achieving HbA1c <7.0%. RESULTS: Comparison between subgroups demonstrated that patients with endpoint HbA1c <7.0% were significantly younger, with a shorter duration of diabetes and lower baseline FPG, HbA1c, body mass index, and dose of premixed insulin than patients with endpoint HbA1c ≥7.0%. Logistic regression analysis revealed a negative correlation between baseline age, HbA1c, FPG, and duration of diabetes with achieving HbA1c <7.0%. When stratified according to change in HbA1c, the improvement group was younger, with higher baseline HbA1c and a greater number of patients with duration of diabetes ≤5 years. Three-quarters of patients unable to achieve HbA1c <7.0% also failed to reach FPG ≤6.1 mmol/L. CONCLUSION: Younger patients with a shorter duration of diabetes and lower HbA1c, FPG, and premixed insulin dose following a switch in treatment to insulin glargine (100 U/ml) plus OADs from premixed insulin have greater potential to achieve HbA1c <7.0%. Poorly controlled patients with higher baseline HbA1c are most likely to experience an improvement in HbA1c following the switch in therapy. The majority of patients unable to achieve HbA1c <7.0% also failed to reach FPG ≤6.1 mmol/L, highlighting the importance of adequate titration of insulin glargine to achieve adequate FPG control, which can enable achievement of target HbA1c. FUNDING: Sanofi.

CD30 Expression in Pediatric Neoplasms, Study of 585 Cases.

CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8), and its normal expression is restricted to activated T and B cells. In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody. CD30 expression has been reported also in mostly adult non-lymphoid malignancies, raising the possibility of CD30-targeted therapy for additional tumors. In this study, we examined the incidence of CD30 expression in 251 hematopoietic and 334 non-hematopoietic cases of pediatric tumors. As expected, strong and membranous CD30 staining was seen in anaplastic large cell lymphoma, classical Hodgkin lymphoma, and embryonal carcinoma while variable staining was seen in diffuse large B cell lymphoma. In addition, positive CD30 staining was also seen in cases of neuroblastoma (33 of 56), neoplasm with chondroid differentiation (8 of 25), myeloid neoplasms (11 of 120), hemangioma (2 of 12), and mature teratoma (1 of 11). In neuroblastoma, the CD30 expression was generally restricted to cells with ganglion differentiation; staining of ganglion cells was also seen in the one positive case of mature teratoma. In neoplasm with chondroid differentiation, the positive cases were chondrosarcoma (3 of 5), chondroblastic osteosarcoma (2 of 10), and chondroblastoma (3 of 7). In acute myeloid leukemia, the CD30 positive cases were more common in AML with monocytic differentiation but did not correlate with any specific molecular change. We conclude that CD30 expression in pediatric tumors is more general than anticipated and future studies are warranted to understand the biologic and therapeutic significances.

Epidemiology of Diarrheal Illness in Pediatric Oncology Patients.

BACKGROUND: Diarrhea is common in children with cancer, but this has not been systematically studied to date. METHODS: Remnant stool samples collected between January 2010 and June 2011 from pediatric oncology patients with diarrhea were tested for bacterial, viral, and parasitic enteropathogens using a combination of standard-of-care (SOC) diagnostic tests, including broad-range, real-time polymerase chain reaction (PCR) assays for adenoviruses, astroviruses, and sapoviruses and 2 commercially available multiplexed PCR assays. Corresponding demographic and clinical data were abstracted from patients' medical records. RESULTS: One hundred fourteen episodes of diarrhea in 93 patients (median age, 3.7 years; range, 0.2-18.8) were included in the study. No patients died, but morbidity was significant. A total of 158 potential pathogens were detected in 114 diarrhea episodes, with >1 organism in one third of these; the most common were Clostridium difficile, noroviruses, adenoviruses, and astroviruses. Clostridium difficile, in combination with norovirus or adenovirus, was most common when >1 pathogen was detected. When both studies were obtained, SOC and broadly multiplexed PCR tests were concordant in 64 episodes (56%). Forty-five pathogens (28%) were identified retrospectively by broadly multiplexed PCR assays only. A total of 19 (13%) were detected by SOC real-time PCR assays but not by either commercially available multiplexed PCR assay. CONCLUSIONS: Most pediatric oncology patients in this study had 1 or more potential infectious causes for their diarrhea. Additional studies are warranted to understand the natural history of gastroenteritis in this patient population. Although broadly multiplexed PCR assays offer some advantages over conventional testing, there may be disadvantages to their use for the diagnosis of infectious gastroenteritis that are unique to pediatric oncology patients.

Comparative study of CD4 and CD45RO T cells and CD20 B cells in cerebrospinal fluid of syphilitic meningitis and tuberculous meningitis patients.

This study was to investigate the differences of lymphocyte in the cerebrospinal fluid (CSF) of patients with syphilis meningitis (SM) and tuberculous meningitis (TBM) for new diagnostic insights. Totally, 79 cases of SM and 45 cases of TBM were enrolled. In the CSF, the CD4, CD45RO or CD20 positive lymphocytes were detected by immunohistochemistry. The proportion of CD4 T cells in the CSF lymphocytes in patients with SM was significantly higher than that in patients with TBM (p < 0.05). After medical therapy, there was a significantly decline trend of the CD4 T-cell proportion in both groups (p < 0.05). The proportion of CD45RO T cells in CSF lymphocytes of patients with SM was less than that of patients with TBM (p < 0.05). After medical therapy, the positive ratio of CD45RO T cells was increased in the CSF of both group patients (p < 0.05). The proportion of CD20B cells in the CSF lymphocytes was not obviously different between the two groups during every stage. In conclusion, there are strong differences of CD4 and CD45RO T-cell ratio, but not the CD20 B cells in the meningitis. CD4 and CD45RO T cells in CSF are a useful complement in differentially diagnosing SM and TBM; it contributes to further understand the pathogenesis and prognosis of SM and TBM.