Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy. Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed. Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases (7.7％),and 96 cases (92.3％) developed CRS. Patients with high-risk cytogenetics had a higher risk of developing CRS (P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) had a lower risk of developing CRS (P=0.004). There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS (P=0.006). The highest body temperature varied among patients with different treatment regimens (P=0.001). The decrease in total protein in patients with CRS was more significant than in patients without CRS (P=0.002). Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS (P=0.037). Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion (P=0.013),while IL-6,C-reactive protein (CRP),and serum ferritin (SF) also showed significant increases (P=0.007,P<0.001,P=0.003). Conclusion:High-risk cytogenetics is a risk factor for severe CRS. Long duration of fever is a clinical characteristic of severe CRS. CRP can better reflect the severity of CRS.

Objective:To investigate and assess hemolytic transfusion reaction in patient with complex and combined anti-Fya and anti-Jkb which so as to provide a safety blood transfusion strategy.Methods:ABO/Rh blood grouping,antibody screening and identification,and Coombs'tests were performed by the routine serological methods include manual tube and automatic blood group analyzer with matching micro-column gel cards from Diagnostic Grifols and Jiangsu LIBO.The hospital information system and laboratory information system were used to collect dada on patients' blood routine tests,liver and kidney function,coagulation,cardiac function,and other clinical indicators before and after blood transfusion were analyzed and compared in conjunction with the patients'clinical manifestations.Results:The patient's blood group was A/CcDEe.Before two transfusion,the anti-body screening were positive which identification were anti-Fya and anti-Fya combined with anti-Jkb respectively,while the Coomb's test were positive with anti-C3 and anti-IgG combined with anti-C3 respectively.No agglutination and hemolysis was observed in saline medium cross-matching test before two transfusion of Fya-red blood cell.But before re-transfusion agglutinated reaction was observed in cross-matching test by DG Gel Coombs,which strength was 2+on whether major or minor side.The patient developed soy sauce urine/hemoglobinuria and fever after transfused Fya-red blood cell again.Primary laboratory indicators were observed to be elevated,include C-reactive protein from 3.06 mg/L to 29.97 mg/L,total bilirubin from 21.4 μmol/L to 276.3 μmol/L,direct bilirubin from 8.4 μmol/L to 135.6 μmol/L,lactate dehydrogenase from 166 U/L to 1453 U/L.Urinary free hemoglobin test was 4+.The main laboratory indicators reflecting the heart,liver,kidney and circulatory coagulation function also have vary increased and gradually returned to normal after a week. Conclusion:Jkb-incompatible transfusion of the Kidd blood group system can lead to acute hemolytic transfusion reaction,but in emergency implementing incompatible transfusion due to IgG antibodies outside of the primary blood group (such as ABO/RhD)can ensure the implementation of emergency operation.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Diabetic kidney disease is an important microvascular complication of diabetes and the leading cause of end-stage renal disease. Its pathological characteristics mainly include epithelial mesenchymal transition(EMT) in glomerulus, podocyte apoptosis and autophagy, and damage of glomerular filtration barrier. Transforming growth factor-β(TGF-β)/Smad signaling pathway is specifically regulated by a variety of mechanisms, and is a classic pathway involved in physiological activities such as apoptosis, proliferation and differentiation. At present, many studies have found that TGF-β/Smad signaling pathway plays a key role in the pathogenesis of diabetic kidney disease. Traditional Chinese medicine has significant advantages in the treatment of diabetic kidney disease for its multi-component, multi-target and multi-pathway characteristics, and some traditional Chinese medicine extracts, traditional Chinese medicines and traditional Chinese medicine compound prescription improve the renal injury of diabetic kidney disease by regulating TGF-β/Smad signaling pathway. This study clarified the mechanism of TGF-β/Smad signaling pathway in diabetic kidney disease by expounding the relationship between the key targets of the pathway and diabetic kidney disease, and summarized the research progress of traditional Chinese medicine in the treatment of diabetic kidney disease by interfering with TGF-β/Smad signaling pathway in recent years, to provide reference for drug research and clinical treatment of diabetic kidney disease in the future.
Humans ; Diabetic Nephropathies/genetics* ; Medicine, Chinese Traditional ; Kidney/pathology* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Epithelial-Mesenchymal Transition ; Smad Proteins/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Diabetes Mellitus/genetics*

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
Commerce ; Medicine, Chinese Traditional ; Tablets ; Water ; Drug Compounding

Humans ; Gemcitabine ; Neoplasms

OBJECTIVE: To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM). METHODS: Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed. RESULTS: After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively. CONCLUSION The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.
Humans ; Receptors, Chimeric Antigen ; Immunotherapy, Adoptive ; Burkitt Lymphoma ; Antigens, CD19 ; Neoplasm, Residual ; Adaptor Proteins, Signal Transducing

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates