[The therapeutic effect and prognostic value of oligoclonal bands after autologous stem cell transplant in patients with multiple myeloma].

Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.

[The characteristics and impact on prognosis of cytopenia after anti-BCMA-CAR-T therapy in patients with relapsed and refractory multiple myeloma].

Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.

[The prognosis and related factors impacting renal response in newly diagnosed multiple myeloma patients with renal impairment].

Objective: To investigate the prognosis and related factors impacting renal response in newly diagnosed multiple myeloma (NDMM) patients with renal impairment. Methods: A total of 375 NDMM patients diagnosed at the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University from August 2012 to April 2022 were retrospectively recruited. Patients were categorized into non-renal impairment group(n=273) and renal impairment group (n=102) according to renal function at initial diagnosis. All patients received≥2 cycles of bortezomib-based induction chemotherapy after admission. The hematological response included stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD). The renal responses were defined as CR, PR, minor response (MR) and non-response (NR). General clinical data of the patients were collected, and patients were followed up by telephone. The follow-up deadline was December 3, 2022, and the median follow-up time [M (Q1, Q3)] was 42 (22, 61) months. Kaplan-Meier analysis was used to plot the survival curve. The log-rank test was utilized for inter-group comparisons. Multivariate logistic regression modeling facilitated the exploration of associated factors impacting renal response. Results: In the renal impairment group, there were 68 males and 34 females with a median age [M (Q1, Q3)] of 64 (58, 69) years. In the non-renal impairment group, there were 149 males and 124 females with a median age of 62 (54, 68) years. Compared with the renal impairment group, the age, lactate dehydrogenase and 24-hour urinary protein quantity were increased, the proportion of patients with light chain M protein and the proportion of patients at the DS-Ⅲ stage, ISS-Ⅲ stage and R-ISS-Ⅲ stage were higher, the hemoglobin level and the proportion of patients receiving autologous hematopoietic stem cell transplantation were lower in the renal impairment group (all P<0.05). In 102 patients with renal impairment, renal responses of CR, PR, MR and NR were obtained in 53 (52.0%), 8 (7.9%), 18 (17.6%), 23 (22.5%) patients, respectively, and the overall response rate was 77.5% (79/102). Kaplan-Meier survival curve revealed that the median progression-free survival (PFS) was 24.0 (95%CI: 18.3-29.7) months in the renal impairment group, which was shorter than 31.0 (95%CI: 24.7-37.3) months in the non-renal impairment group (P=0.003). The median overall survival (OS) was 46.0 (95%CI: 36.5-55.5) months in the renal impairment group, which was shorter than 79.0 (95%CI: 59.9-98.1) months in the non-renal impairment group (P=0.002). Among the renal impairment group, patients with renal response of less than PR exhibited a median PFS of 19.0 (95%CI: 9.7-28.3) months, which was shorter than 28.0 (95%CI: 21.4-34.5) months for those achieving PR or better (P=0.048). The median OS was 31.0 (95%CI: 23.5-38.5) months in renal response with less than PR group, which was also worse than 57.0 (95%CI: 42.8-71.2) months for those who achieved PR or better (P=0.003). The results of multivariate logistic regression showed that hematological response achieving VGPR or better was a factor associated with renal response achieving PR (OR=4.20, 95%CI: 1.20-14.68, P=0.025). Conclusions: The prognosis of NDMM patients with renal impairment is poor. The hematological response with VGPR or better is related to the renal response achieving PR.

Electron-Scale Reconnection in Three-Dimensional Shock Turbulence.

Magnetic reconnection has been observed in the transition region of quasi-parallel shocks. In this work, the particle-in-cell method is used to simulate three-dimensional reconnection in a quasi-parallel shock. The shock transition region is turbulent, leading to the formation of reconnecting current sheets with various orientations. Two reconnection sites with weak and strong guide fields are studied, and it is shown that reconnection is fast and transient. Reconnection sites are characterized using diagnostics including electron flows and magnetic flux transport. In contrast to two-dimensional simulations, weak guide field reconnection is realized. Furthermore, the current sheets in these events form in a direction almost perpendicular to those found in two-dimensional simulations, where the reconnection geometry is constrained.

[A study on longitudinal changes in white matter microstructure of parents who have lost their only child based on diffusion tensor imaging and its relationship with symptoms of posttraumatic stress disorder].

Objective: To investigate the longitudinal changes of white matter microstructural based on diffusion tensor imaging in parents who lost their only child without psychiatric disorders and its relationship with symptoms of posttraumatic stress disorder (PTSD). Methods: Parents who had who lost their only child and without psychiatric disorders in Jiangsu Province, from September 2016 to March 2017, were retrospectively collected (TENP group, 32). MRI scans were performed at baseline and at the end of 5-year follow-up, and the Clinician Administered PTSD Scales (CAPS) were used for assessing the severity of symptoms. Additionally, sex, age and education level matched healthy subjects were recruited as healthy controls (control group, 27) and underwent MRI scanning using the same protocol. The differences of fractional anisotropy (FA) values between TENP group and control group at baseline were analyzed by using Tract-based spatial statistics method, and the brain areas of lateral differences were used as the regions of interest for longitudinal follow-up analysis of TENP group. Partial correlation analysis was used to evaluate the relationship between FA values changes in longitudinal differences in brain regions and CAPS scores. Results: Compared with the control group, FA values of the right cingulate gyrus, Uncinate fasciculus, superior longitudinal fasciculus, corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major in TENP group were decreased at baseline ((0.613±0.032) vs (0.631±0.034), (0.539±0.048) vs (0.563±0.045), (0.534±0.033) vs (0.558±0.039), (0.560±0.038) vs (0.580±0.030), (0.519±0.023) vs(0.549±0.024), (0.489±0.038) vs (0.518±0.027), (0.499±0.027) vs (0.533±0.032); all P<0.05). From baseline to follow-up, scores of trauma reexperience symptoms and avoidance/numbness symptoms were decreased ((5.2±2.8) vs (8.1±4.9), (4.0±3.2) vs (6.6±5.4); all P<0.05); FA values of the right corticospinal tract, Inferior fronto-occipital fasciculus, Inferior longitudinal fasciculus and forceps major were decreased ((0.523±0.049) vs (0.537±0.049), (0.568±0.052) vs (0.590±0.050), (0.540±0.063) vs (0.559±0.059), (0.520±0.059) vs (0.547±0.059); all P<0.05); The decrease of FA values of the right Inferior fronto-occipital fasciculus and right Inferior longitudinal fasciculus was negatively correlated with the decrease of avoidance/numbness symptoms scores (r=-0.458, -0.374, respectively, all P<0.05). Conclusions: The trauma of parents who lost their only child can result in impaired microstructural integrity of white matter. As the post-traumatic time goes by, parents who have lost their only child do not develop to PTSD and other psychiatric disorders, and the clinical symptoms are alleviated, the damage of the white matter microstructure continued to progress.

Lipocalin-2: a role in hepatic gluconeogenesis via AMP-activated protein kinase (AMPK).

PURPOSE: Evidence is accumulating that lipocalin2 (LCN2) is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase (AMPK) or forkhead transcription factor O1 (FoxO1), which influences insulin sensitivity and gluconeogenesis in liver. METHODS: LCN2 knockout (LCN2KO) mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic gluconeogenesis through pyruvate tolerance test (PTT), glucose tolerance test (ipGTT), insulin tolerance test (ITT), and hyperinsulinemic-euglycemic clamps, respectively. LCN2KO mice and WT mice in vivo, and in vitro HepG2 cells were co-transfected with adenoviral FoxO1-siRNA (Ad-FoxO1-siRNA) or adenovirus expressing constitutively active form of AMPK (Ad-CA-AMPK), or dominant negative adenovirus AMPK (Ad-DN-AMPK), the relative mRNA and protein levels of two key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) were measured. RESULTS: Improved insulin sensitivity and inhibited gluconeogenesis in the LCN2KO mice were confirmed by pyruvate tolerance tests and hyperinsulinemic-euglycemic clamps. Nuclear FoxO1 and its downstream genes PEECK and G6P were decreased in the livers of the LCN2KO mice, and AMPK activity was stimulated and directly phosphorylated FoxO1. In vitro, AMPK activity was inhibited in HepG2 cells overexpressing LCN2 leading to a decrease in phosphorylated FoxO1 and an increase in nuclear FoxO1. CONCLUSION: The present study demonstrates that LCN2 regulates insulin sensitivity and glucose metabolism through inhibiting AMPK activity, and regulating FoxO1 and its downstream genes PEPCK/G6P, which regulate hepatic gluconeogenesis.

Efficacy and safety of iguratimod combined with methotrexate vs. methotrexate alone in rheumatoid arthritis : A systematic review and meta-analysis of randomized controlled trials.

The current systematic review and meta-analysis aims to evaluate the efficacy and safety of iguratimod (IGU) combined with methotrexate (MTX) versus MTX alone in rheumatoid arthritis (RA). Two independent investigators searched for original randomized controlled trials (RCTs) related to the combination of IGU and MTX in RA published before November 1, 2019, in PubMed, Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), and WanFang Data. Additionally, we searched clinical trial registry websites. We assessed the methodological quality of the included trials using the Cochrane Collaboration tool and the seven-point Jadad scale. Statistical analyses were performed using Review Manager (RevMan) 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Meta-regression and publication bias analyses were performed using Stata version 14 software (StataCorp., College Station, TX, USA). A total of 7 RCTs consisting of 665 participants, with 368 participants in the active arm and 297 in the placebo arm, were included in the meta-analysis. The American College of Rheumatology (ACR) value was better in the IGU + MTX group than in the MTX alone group, with a pooled relative risk (RR) for ACR20 (American College of Rheumatology 20% improvement criteria), ACR50, and ACR70 of 1.40 (95% CI, 1.13-1.74), 2.09 (95% CI, 1.67-2.61), and 2.24 (95% CI, 1.53-3.28), respectively. The results of the meta-analysis demonstrated that there was no statistical significance in adverse events (1.06 (95% CI, 0.92-1.23)). The combined treatment is an effective, safe, and economical treatment option for patients who do not respond well to methotrexate alone or for patients who cannot afford expensive biologics that have no confirmed efficacy.

[Effects of remote ischemic preconditioning on contrast-induced acute kidney injury after percutaneous coronary intervention in patients with chronic total occlusion].

Objective: To investigate the effect of remote ischemic preconditioning (RIPC) on contrast-induced acute kidney injury (CI-AKI) in patients with chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). Methods: A total of 282 patients undergoing PCI at Zhongda Hospital Affiliated to Southeast University between June 2017 and January 2019 were prospectively enrolled. The patients were randomly divided into RIPC group (n=142) and control group (n=140). CI-AKI was defined as an increase in level of cystatin C (CysC)≥10% above baseline at 24 h after contrast administration. Baseline characteristics and the incidence of CI-AKI were compared between the two groups. The multivariate logistic regression analysis was further used to analyze the independent risk factors of CI-AKI. Results: There were no significant differences in age, gender, smoking, hypertension, diabetes, stroke and old myocardial infarction, coronary artery bypass graft surgery, previous PCI history and laboratory test indicators, target vessel and pathological characteristics of CTO lesions, contrast agent dosage, J-CTO (Multicenter CTO Registry in Japan) score, SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score, PCI success rate and stent number between the two groups (P>0.05). The incidence of CI-AKI was significantly lower (18.3% vs 29.3%, P=0.036) in RIPC group than that of control group. Multivariate logistic analysis found that creatinine [odds ratio (OR)=1.018,95%CI: 1.006-1.030, P=0.003], CysC (OR=5.200, 95%CI:2.714-9.963, P<0.001),contrast agent dosage (OR=1.013,95%CI: 1.007-1.019, P<0.001) and J-CTO score (OR=1.834, 95%CI: 1.145-2.939, P=0.012) were independent risk factors of CI-AKI. However, RIPC was an independent protective factor of CI-AKI (OR=0.391, 95%CI: 0.199-0.765, P=0.006). Conclusion: RIPC before contrast agent administration prevents CI-AKI in CTO patients undergoing PCI.

[Evaluation of fast nucleic acid detection system in severe acute respiratory syndrome coronavirus 2].

Objective: To evaluate the performance and application of a fast nucleic acid detection system for testing severe acute respiratory syndrome virus 2 (SARS-COV-2). Methods: Clinical samples were collected from February to July 2020 from Beijing Center for Diseases Prevention and Control and the Laboratory Department of China-Japan Friendship Hospital, to evaluate the sensitivity, specificity, anti-interference ability, precision and clinical sample coincidence rate of fast nucleic acid detection system for SARS-CoV-2. The analytical sensitivity was determined by a dilution series of 20 replications for each concentration. Analytical specificity study was performed by testing organisms whose infection produces symptoms similar to those observed at the onset of corona virus disease 2019 (COVID-19), and of the normal or pathogenic microflora that may be present in specimens collected. Potential interference substances were evaluated with different concentration in the interference study. Precision study was conducted by estimating intra-and inter-batch variability. Clinical evaluation was performed by testing 230 oropharyngeal swab specimens and 95 sputum specimens in fast nucleic acid detection system, comparing with conventional real-time fluorescent quantitative PCR (RT-qPCR) and clinical diagnostic results. Results: The analytical sensitivity of SARS-CoV-2 using fast nucleic acid detection system was 400 copies/ml. The result is negative for testing with the organisms that may likely in the circulating area or causing similar symptoms with SARS-CoV-2 and human nucleic acid, indicating that no cross reactivity with organisms. The results of precision test showed that the Coefficient of variation of Ct value of high, medium and low concentration samples was 1.90%-3.92%, and all of them were less than 5% in intra-and inter-batch testing. The results of the samples were still positive after adding the potential interfering substances, indicating that the possible interfering substances in the samples had no effect on the results. 98.46% and 97.85% diagnosis results of fast nucleic acid detection system were consistent with RT-qPCR and clinical diagnostic results, respectively. Conclusion: The fast nucleic acid detection system based on molecular parallel reaction can be used as a selection method for SARS-CoV-2 testing.

[Clinical features of children with cow's milk sensitization].

Objective: To investigate sensitization rate of cow's milk in children, and explore its clinical features. Methods: This study enrolled a total of 818 patients under 18 years old with suspected food allergy who were admitted to the Allergy department in Beijing Shijitan Hospital during June 2018 to November 2020. The ImmunoCAP fluorescent enzyme-linked immunoassay system was used to quantify cow milk-specific immunoglobulin E (sIgE). Mild sensitization to cow's milk was defined as Radio-Allergo-Sorbent-Test (RAST) class 1, moderate sensitization was defined as class 2-3 and severe sensitization was class 4-6. Statistical methods such as χ2 test, independent sample t-test, one-way analysis of variance, and Spearman correlation analysis were used to retrospectively clarify differences of cow's milk sensitization rate between ages of children and elaborate its clinical features. Results: Overall sensitization rate of cow's milk reached 25.7% (210/818). Positive rate of cow milk sensitization (39.2%), cow milk sIgE levels [0.93 (0.52, 2.62)] kU/L, and moderate to severe sensitization rate (23.5%) were highest in infants aged between 0-3 years old. The sensitization rate and severity of sensitization declined with age. Most common clinical manifestation of cow milk sensitization was skin symptoms (50.0%), followed by respiratory symptoms (38.9%) and gastrointestinal symptoms (36.1%). Skin symptoms were the most common manifestation in 0-3 year-old group (47.3%), and respiratory symptoms were more common in 4-6 and 7-18 year-old groups (58.7%, 56.0%). Multiple-sensitization rate of patients with moderate to severe cow milk sensitization was 74.1%, most of which (70.4%) were co-sensitized by other food allergens, and 31.5% were co-sensitized by inhaled allergens. Conclusions: In population with age under 18 years old, infants aged between 0-3 years old suffered highest cow milk sensitization rate and increased sensitization severity. Then the severity decreased with age increasing. Patients with cow milk sensitization manifested skin symptoms most.

[Prognosis and related risk factors of acute respiratory distress syndrome in elder patients].

Objective: To study the risk factors associated with the hospital survival rate of elder patients with acute respiratory distress syndrome (ARDS) in Medical/Respiratory Intensive Care Units (MICUs/RICUs) by evaluating the prognosis, and therefore to provide insight into patient treatment strategy. Methods: Twenty MICUs/RICUs of 19 general hospitals in mainland China participated in the multicenter prospective cohort study carried out from Mar 1st, 2016 to Feb 28th, 2018. Patients who met the criteria of Berlin ARDS and older than 65 years were recruited. Baseline data, risk factors of ARDS, ventilator setup and prognosis data were collected from all patients. Univariant and multivariant regression analysis were conducted to analyze the factors associated with the prognosis. Results: 170 elder ARDS patients (age≥65 years) met the Berlin ARDS criteria, among whom 8.8% (15/170), 42.9% (73/170) and 48.2% (82/170) patients had mild, moderate and severe ARDS, respectively. The most common predisposing factor for elder ARDS was pneumonia, which was present in 134 patients (78.8%). 37.6% (64/170) patients were treated with noninvasive mechanical ventilation (NIV), but 43.8% (28/64) cases experienced treatment failure. 76.5% (130/170) patients were treated with invasive mechanical ventilation. All patients 80 years or older were given invasive mechanical ventilation. 51.8% (88/170) cases had complications of non-pulmonary organ failure. 61.8% (105/170) patients deceased during hospital stay. Multivariant logistic analysis showed that the independent risk factors for hospital survival rate in elder patients with ARDS were SOFA score (P=0.030, RR=0.725, 95% CI 0.543-0.969), oxygen index after 24 hours of ARDS diagnosis (P=0.030, RR=0.196, 95% CI 0.045-0.853), accumulated fluid balance within 7 days after diagnosis of ARDS (P=0.026, RR=1.000, 95% CI 1.000-1.000) and shock (P=0.034, RR=0.140, 95% CI 0.023-0.863). Conclusion: Among 20 ICUs, the high mortality rate of elder patients with ARDS was correlated with higher 24 hour SOFA score, lower 24 hour oxygen index after ARDS diagnosis, more positive fluid balance within 7 days and concomitant shock. The conservative fluid strategy within 7 days of ARDS diagnosis may benefit the elder ARDS patients.

Lower-Hybrid Drift Waves Driving Electron Nongyrotropic Heating and Vortical Flows in a Magnetic Reconnection Layer.

We report measurements of lower-hybrid drift waves driving electron heating and vortical flows in an electron-scale reconnection layer under a guide field. Electrons accelerated by the electrostatic potential of the waves exhibit perpendicular and nongyrotropic heating. The vortical flows generate magnetic field perturbations comparable to the guide field magnitude. The measurements reveal a new regime of electron-wave interaction and how this interaction modifies the electron dynamics in the reconnection layer.

Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

Survey of infection and determination of the transmission vector of Onchocerca fasciata in camels (Camelus bactrianus) in Inner Mongolia, China.

Onchocerciasis in camels is caused by adult Onchocerca spp. and results in great economic losses to the camel industry. However, only a few studies on Onchocerca have been conducted, especially regarding the intermediate host and vector(s). In the present study, 192 camels were examined from December and January during 2013 and 2016, and the filarial larvae suspected to be Onchocerca spp. were further identified. Furthermore, aquatic dipteran insects in the living environment of camels were collected from May to September between 2013 and 2017 and dissected. Eventually, onchocercal lesions were observed in 95 of 192 (49%) camels and the captured insects were classified into 49 species from 42 genera in 21 families, among which 18 species were newly recorded in Inner Mongolia and 14 were haematophagous species. The filarial larvae were found in Culicoides puncticollis and identified as Onchocerca fasciata, indicating that C. puncticollis is the vector of O. fasciata in Inner Mongolia. These findings provide an estimate of onchocerciasis infection in camels and an alternative method of identifying insects and screening vectors using molecular methods. Important data are also provided for the diagnosis and control of onchocerciasis, thereby further filling the gap in knowledge regarding transmission vectors in China.

[Application of plasma glucosylsphingosine detection in the follow-up of patients with Gaucher disease].

Objective: Explore the application of plasma glucosylsphingosine level in the follow-up treatment of patients with Gaucher disease. Methods: Two groups of patients with Gaucher disease were enrolled, who regularly received imiglucerase treatment in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between January 2017 and July 2020. Group 1 was 6 initially treated patients, including 1 case of chitotriosidase deficiency, aged 10-43 years old, 4 females and 2 males. The blood routine test, chitotriosidase activity and plasma glucosylsphingosine level were measured during pre-and post-treatment. Group 2 were 6 cases of Gaucher disease including 3 cases of chitotriosidase deficiency, who received long-term specific treatment in the same hospital, aged 17 to 32 years, 2 females and 4 males. The plasma glucosylsphingosine level was detected in the follow-up treatment during January 2017 to July 2020. Results: Patients in group 1 had a significant increase in plasma platelets after 12 months of treatment (P<0.05), and also a significant increase in plasma hemoglobin after 30 months of treatment (P<0.05). The chitotriosidase activity of 5 patients in group 1 significantly decreased after 18 months of treatment (P<0.05), the median value of the chitotriosidase activity decreased by 7 278 nmol·ml(-1)·h(-1) at 30 months of treatment. While only 3 months after treatment, the plasma glucosylsphingosine levels of 6 patients in group 1 decreased significantly (P<0.05), the median value of the glucosylsphingosine levels decreased by 259.7 µg/L at 30 months of treatment. The plasma glucosylsphingosine levels in group 1 patients were positively correlated with chitotriosidase activity, with spearman of 0.863, P<0.001. In group 2, 6 patients with Gaucher disease that had been treated for a long period of time, showed normal peripheral blood routine tests, normal liver and spleen volume. However, the plasma glucosphingosine levels in group 2 patients decreased significantly during 2017-2020 (P<0.05). Compare to the initial values, the median value of the last glucosphingosine levels in group 2 patients had been reduced by 23.4 µg/L. Conclusion: The detection of plasma glucosylsphingosine levels in patients with Gaucher disease could be used for short-term and long-term follow-up of treatment.

[Analysis of pathogenic composition and clinical characteristics of viral acute gastroenteritis in children under five years old in Beijing].

Objective: To understand the epidemiological characteristics and clinical features of rotavirus-, norovirus-, adenovirus-and astrovirus-associ ated acute gastroenteritis in children under 5 years old in Beijing from Octorber, 2015 to March, 2017. Methods: In the intestinal clinic of 6 hospitals in 6 districts of Beijing, information and stool samples of the first 30 patients with acute gastroenteritis who are under the age of 5 years are collected monthly.Rotavirus, norovirus, adenovirus and astrovirus are identified by PCR.Descriptive epidemiological method was used to describe the epidemiological characteristics of diarrhea caused by rotavirus, norovirus, adenovirus and astrovirus in Beijing. One-way analysis of variance was used to analyze the Vesikari clinical severity score of of acute gastroenteritis caused by each virus. Unconditional logistic regression analysis was used to analysis the associated factors of clinical features. Results: Of the 2 052 samples, 709 (34.6%) were non-mixed infections: the positive rate of rotavirus, norovirus, adenovirus and astrovirus were 20.0%, 7.5%, 4.2% and 2.9%, respectively. A total of 135 cases (6.6%) were mixed infection. The mean and standard deviation of Vesikari clinical severity score was 8.0±3.1 for rotavirus associated acute gastroenteritis, which was significantly higher than norovirus (6.4±2.4, P<0.001), adenovirus (6.2±2.1, P<0.001) and astrovirus (6.1±2.0, P<0.001). The comparison of clinical features showed that compared with astrovirus, the children under 5 years old infected with rotavirus were more likely to have a diarrhea ≥5 days (OR=3.334), have vomiting ≥3 times within one day (OR=8.788), have vomiting≥1 day (OR=3.963), have a Vesikari clinical severity score ≥11 severe cases (OR=13.194). Norovirus infected cases were prone to have vomiting≥3 times in 1 day (OR=5.710).Adenovirus infected cases were prone to have a diarrhea≥5 days (OR=2.616). When using rotavirus as a reference, children under 5 years of age were less likely to develop fever≥38.4 ℃ after infection with norovirus (OR=0.397) or adenovirus (OR=0.280). Conclusions: The results of this study showed that the characteristics of acute gastroenteritis caused by different viruses are different. The clinical symptoms caused by rotavirus are more serious. Children under 24 months of age are at high risk of rotavirus infection. Effective preventive measures such as vaccination should be taken as soon as possible.

Retrospective Analysis of 291 Cases of Medical Malpractice Involving Death.

ABSTRACT: Objective To study the medical malpractice cases involving death, and discuss the identification ideas and methods of medical malpractice cases. Methods A total of 291 medical malpractice cases involving death accepted and settled from January 2012 to December 2017 at the Judicial Appraisal Center of Southern Medical University were collected. Based on the age, gender, hospital level, clinical department, whether or not autopsy was performed, cause of death, cause of medical mistakes, causality and causative potency of the appraised person, statistical analysis was made. Results There were more males than females in medical malpractice cases involving death. Mostly young adults or children were involved in these cases. The number of cases involving tertiary hospitals was the highest; among the clinical departments, the internal medicine department had the largest number of cases, followed by surgery, obstetrics and gynecology, pediatrics, etc. Autopsy rate has a trend of increasing year by year. Most patients die from the natural outcomes of their disease or ineffective treatment. Most hospitals have certain medical mistakes, and have an indirect correlation with the patient's death, mainly slight factors. Conclusion Judicial appraisal of medical malpractice should follow the principle of "one-effect and multi-cause", and comprehensively consider various factors such as, the diseases and constitution of the patient, natural outcomes of the diseases, the current medical technology and the level of diagnosis and treatment of the hospital, etc.

Differential expression profile of hepatic circular RNAs in chronic hepatitis B.

CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs associated with CHB, we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB-associated circRNAs and in silico analysis of the circRNA-miRNA-mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA-miRNA-mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB-related circRNA-miRNA-mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV-associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFß2 and a negative correlation between hsa_circ_0000650 and miR-6873-3p, which hinted that hsa_circ_0000650 interacted with TGFß2 mediated by miR-6873-3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.

Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock.

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.