[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 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.

[Validation of the prognostic value of the Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma: A single-center study].

Objective: To evaluate the prognostic value of Mayo MASS and R2-ISS staging systems in patients newly diagnosed with multiple myeloma (MM) . Methods: A total of 371 patients newly diagnosed with MM in Jiangsu Province Hospital were included in the study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was performed to detect cytogenetic abnormality. Clinical characteristics were combined to analyze the disease stage and evaluate the prognosis. Results: There were 37 (10.0%), 264 (71.0%), and 70 (18.8%) patients in R-ISS stage Ⅰ, Ⅱ, and Ⅲ, respectively. The median progression-free survival (PFS) times were 37, 25, and 14 months (P<0.001). The median overall survival (OS) times were not reached (NR), 66, and 30 months (P<0.001). There were 71 (19.1%), 140 (37.7%), and 160 (43.2%) patients in Mayo MASS stages Ⅰ, Ⅱ, and Ⅲ, and the median PFS times periods were 43, 27, and 19 months (P<0.001), and the median OS times were NR, NR, 35 months, respectively (P<0.001). There were, 23 (6.2%), 69 (18.6%), 222 (59.8%), and 57 (15.4%) patients in R2-ISS stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. The median PFS times were 47, 31, 25, and 15 months (P=0.001), and the median OS times were NR, NR, 49, and 55 months, respectively (P<0.001) . Conclusion: Based on the R-ISS staging system, Mayo MASS, and R2-ISS prognostic staging system incorporated 1q21+, which allows a better stratification. However, the proportion of stage Ⅲ patients in Mayo MASS and R2-ISS staging systems is relatively high, which is considered related to the high incidence of 1q21+ and ISS Ⅲ in the Chinese population.

Laboratory Study of Collisionless Magnetic Reconnection.

A concise review is given on the past two decades' results from laboratory experiments on collisionless magnetic reconnection in direct relation with space measurements, especially by the Magnetospheric Multiscale (MMS) mission. Highlights include spatial structures of electromagnetic fields in ion and electron diffusion regions as a function of upstream symmetry and guide field strength, energy conversion and partitioning from magnetic field to ions and electrons including particle acceleration, electrostatic and electromagnetic kinetic plasma waves with various wavelengths, and plasmoid-mediated multiscale reconnection. Combined with the progress in theoretical, numerical, and observational studies, the physics foundation of fast reconnection in collisionless plasmas has been largely established, at least within the parameter ranges and spatial scales that were studied. Immediate and long-term future opportunities based on multiscale experiments and space missions supported by exascale computation are discussed, including dissipation by kinetic plasma waves, particle heating and acceleration, and multiscale physics across fluid and kinetic scales.

[The impact of low T3 syndrome on the prognosis of patients with newly diagnosed multiple myeloma].

Objective: This study aimed to examine the relationship between low T3 syndrome (LT3S) and the prognosis of newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective examination of 211 NDMM patients treated at the Department of Hematology, Jiangsu Provincial People's Hospital from July 2009 to December 2020 was performed, and all patients received thyroid function testing to determine if they had LT3S. We investigated the relationship between LT3S and clinical features, as well as its impact on MM prognosis. Results: Of the 211 patients, 119 were males, and 92 were females, with a median age of 60 (33-86) years. Patients with LT3S had significantly higher levels of ß(2)-microglobulin, C-reactive protein, and blood creatinine compared to those with normal T3 levels. They also had lower levels of hemoglobin, platelets, and serum albumin, as well as more advanced ISS stages (P<0.001) . Patients with LT3S had shorter progression-free survival (PFS) (16 months vs 30 months, P=0.003) and overall survival (OS) (57 months vs 75 months, P=0.004) than patients without LT3S. LT3S was found to be a standalone unfavorable factor in multivariate analysis, LT3S was an independent unfavorable factor in predicting both PFS (HR=2.114, 95% CI 1.271-3.516, P=0.004) and OS (HR=2.231, 95% CI 1.088-4.577, P=0.029) . Conclusions: Low T3 syndrome was an independent unfavorable prognostic predictor for NDMM.

[Clinical study of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of FLT3-ITD(+) acute myeloid leukemia with normal karyotype].

Objective: To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD(+) acute myeloid leukemia (AML) with normal karyotype. Methods: The clinical data of FLT3-ITD(+) AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results: The study included 49 patients with FLT3-ITD(+)AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD(+) (P>0.05) . There were 12 patients with high-frequency FLT3-ITD(+) in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion: Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD(+) patients, particularly those with FLT3-ITD high-frequency mutation.

[Clinical characteristics and prognosis of newly diagnosed multiple myeloma patients with FGFR3 gene mutations].

Objective: This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients. The prognostic significance of FGFR3 mutation and clinical features were analyzed using the Log-rank test and Cox proportional hazards model. Results: Among 198 patients, 28 carried the FGFR3 gene mutation. These patients had significantly lower serum albumin levels, higher ß(2)-microglobulin levels, advanced Revised International Staging System stages, more frequent occurrence of t (4;14) , and shorter median progression-free survival (PFS) time (28 months vs 33 months, P=0.024) and overall survival (OS) time (54 months vs undefined, P=0.028) than patients without FGFR3 mutation. Additionally, patients carrying either FGFR3 mutation or t (4;14) had lower PFS (30 months vs 38 months, P=0.012) and OS (54 months vs undefined, P=0.017) than those without. The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. Conclusion: FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.

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.

[Influence of the number of high-risk cytogenetic abnormalities on the clinical characteristics and prognosis in 360 patients with newly diagnosed multiple myeloma].

Objective: To investigate the influence of the number of high-risk cytogenetic abnormalities (HRCA) on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (MM) . Methods: A total of 360 patients with newly diagnosed MM admitted to Jiangsu Province Hospital between November 2013 and September 2020 were included in this study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was used to detect HRCA. Cytogenetic abnormalities were combined with clinical characteristics and outcomes for further analysis. Results: Among the 360 patients, 120 patients (33.3%) presented with no HRCAs, and 175 (48.6%) , 61 (16.9%) , and four (1.1%) patients had one, two, and three HRCA (s) , respectively. Patients were divided into three groups, including the no-HRCA group, one-HRCA group, and ≥two-HRCA group, according to the number of HRCAs. There were significant differences in the R-ISS stage, hemoglobin level, albumin level, and the proportion of bone marrow plasma cells among the three groups (P<0.05) . The COX proportional-hazards model identified extramedullary disease (P=0.018) , HRCA ≥ 2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P<0.001) as independent risk factors for progression free survival (PFS) and identified lactate dehydrogenase (LDH) level ≥ 220 U/L (P<0.001) , HRCA ≥2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P=0.005) as independent risk factors for overall survival (OS) . The median PFS was 28 months, 22 months, and 14 months (P=0.005) for the three cohorts, and their OS was not reached,60 months, and 30 months (P=0.001) , respectively. Conclusions: HRCA ≥ 2 is an independent risk factor for decreased survival in patients with newly diagnosed MM. More HRCAs result in heavier tumor burden, as well as a higher risk of disease progression and death.

[In vitro pharmacodynamic studies of novel class â and â ¡b selective histone deacetylase inhibitor purinostat mesylate in the treatment of diffuse large B-cell lymphoma and its mechanism].

Objective: To investigate the in vitro inhibitory activity of a novel class Ⅰ and Ⅱb selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism. Methods: The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot. Results: PM significantly inhibited the proliferation of lymphoma SUDHL-4 and SUDHL-6 cells and increased the acetylation levels of HDAC substrates H3, H4, and α-tubulin. In cell cycle experiments, PM induced G(0)/G(1) phase arrest in SUDHL-4 and SUDHL-6 cells. Western blot experiment showed that PM could significantly downregulate the expression of cyclin-dependent kinases Cdk2, Cdk4, Cdk6, cyclin D1, and cyclin E and upregulate the expression of CDK inhibitor protein p21. In the apoptosis experiment, PM could induce the apoptosis of SUDHL-4 and SUDHL-6 cells. Western blot experiment demonstrated that PM promoted endogenous apoptosis by activating caspase-3 kinase and affecting antiapoptotic protein Bcl-2. In addition, PM could downregulate the expression of oncogene marker proteins MYC, IKZF1, and IKZF3. Conclusion: PM has an efficient biological activity in vitro for diffuse large B-cell lymphoma, including double-hit lymphoma, and provides valuable experimental evidence for PM in clinical treatment.

Hybrid Simulations of the Cusp and Dayside Magnetosheath Dynamics Under Quasi-Radial Interplanetary Magnetic Fields.

Under quasi-radial interplanetary magnetic fields (IMF), foreshock turbulence can have an impact on the magnetosheath and cusps depending on the location of the quasi-parallel shock. We perform three-dimensional simulations of Earth's dayside magnetosphere using the hybrid code HYPERS, and compare northward and southward quasi-radial IMF configurations. We study the magnetic field configuration, fluctuations in the magnetosheath and the plasma in the regions around the northern cusp. Under northward IMF with Earthward B x , there is a time-varying plasma depletion layer immediately outside the northern cusp. In the southward IMF case, the impact of foreshock turbulence and high-speed jets, together with magnetopause reconnection, can lead to strong density enhancements in the cusp.

[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.

[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.

Treatment and long-term outcome of breast cancer in very young women: nationwide population-based study.

BACKGROUND: The study aimed to assess the correlation between long-term survival and treatment in very young women with breast cancer. METHODS: Data on women with breast cancer were retrieved from the Taiwan Cancer Registry between 2004 and 2014. Patients who did not undergo surgery or who had stage 0 or IV disease were excluded. Survival analysis was conducted. The participants were divided into very young (20-29.9 years), young (30-39.9 years), and adult (40-50.0 years) groups. RESULTS: Among 104 115 women, 24 474 (572 very young, 5565 young, and 18 337 adult) were eligible for the study. Median follow-up was 79.5 (range 24-158) months. The mortality rates in the very young, young, and adult groups were 12.9, 10.0, and 8.2 per cent respectively (P < 0.001). Very young patients had higher histological grade, unfavourable subtype, higher TNM stage, and received more breast-conserving surgery (BCS). Kaplan-Meier survival analysis showed that very young patients had the poorest long-term survival. Very young patients with stage II disease had the worst prognosis. In the multivariable regression model, radiotherapy was associated with decreased local recurrence but not with improved overall, cancer-specific, or disease-free survival for stage II disease in the very young group. Surgery type and chemotherapy were not associated with significant improvement in overall survival. CONCLUSION: Very young patients with stage II disease had poor long-term outcomes. BCS had no detrimental effects on long-term outcomes.

[Scoping review on prevention of central venous catheter-related bloodstream infection in burn patients].

Objective: To investigate the research trend and scope of prevention of central venous catheter-related bloodstream infection (CRBSI) in burn patients. Methods: The scoping review method was adopted. Pre-retrieval was carried out with search terms of ", , " and "central venous catheter, infection, catheter-related bloodstream infection, burn". On the basis of pre-retrieval, different retrieval formulas were formulated to retrieve researches related to central venous CRBSI in burn patients in China National Knowledge Internet, Wanfang Database, VIP Database, PubMed, Embase, CINAHL, and Cochrane Library from the establishment of each database to August 2020. Data were extracted from the included literature, including the first author, research publication time, research country, research type, diagnosis basis and intervention measures of central venous CRBSI, research sample selection, incidence related to infection, and research conclusion. Results: A total of 20 randomized controlled trials, quasi-experimental studies, case-control studies, cohort studies, and implementation researches published in 1990-2020 were included in this study with the first authors from China, the United States of America, or Argentina. The diagnostic bases for central venous CRBSI in burn patients were not uniform in the included literature, including adopting the Guidelines of American Centers for Disease Control and Prevention, Diagnostic Criteria for Nosocomial Infection, and other diagnostic criteria without specifying the source. The intervention measures included the use of new materials such as antibiotics coated catheter and ethanol impregnated port protectors, multidisciplinary cooperation, and comprehensive preventive measures. The sample size in the included literature was small, and the sample selection was different, including the number of patients and the the number of placement of central venous catheter. The outcome indicators for infection in the included literature were diversified. The incidence per 1 000 days of central venous CRBSI was 20.41‰-29.1‰ of patients in control group in China, the incidence per 1 000 days of central venous CRBSI was mostly <16.6‰ in control group in foreign countries, and the incidence of central venous CRBSI was decreased to varying degrees after implementing the corresponding intervention measures. Related research conclusions showed that new materials, multidisciplinary cooperation, and comprehensive preventive measures had good effects on prevention of central venous CRBSI in burn patients. Conclusions: The researches on prevention of central venous CRBSI in burn patients in China start early and the research types are diversified. The diagnostic criteria of central venous CRBSI in burn patients are not uniform, intervention measures have shifted from standardizing relevant operational measures to exploring the prevention effects of new materials, multidisciplinary cooperation, and multiple measures, and the latter has good effects on preventing central venous CRBSI in burn patients.

[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.