OBJECTIVE: To observe the efficacy of chimeric antigen receptor T cell (CAR-T) in the treatment of children with refractory/recurrent B acute lymphocytic leukemia (B-ALL). METHODS: Thirty-two patients with r/r B-ALL were treated by CAR-T, the recurrence and death respectively were the end point events to evaluate the efficacy and safety of CAR-T. RESULTS: The median age of the patients was 7.5 (2-17.5) years old; 40 times CAR-T were received in all patients and the median number of CAR-T was 0.9×107/kg; efficacy evaluation showed that 2 cases died before the first evaluation. Thirty patients showed that 3, 6, and 9-moth RFS was (96.3±3.6)%, (81.4±8.6)% and (65.3±12.5)%, respectively, while 3, 6, and 9-month OS was all 100%, and 12, 24-month OS was (94.7±5.1)% and (76±12.8)%. BM blasts≥36% before reinfusion and ferritin peak≥2 500 ng/ml within two weeks of CAR-T cell reinfusion were associated with recurrence. Adverse reactions mainly included cytokine release syndrome (CRS) and CART-cell-related encephalopathy syndrome (CRES), CRS appeared in 26 patients within a week of CAR-T cell reinfusion. CRES reaction was detected in 12 patients. Eighteen patients received intravenous drip of tocilizumab, among them, 12 combined with glucocorticoid. CRS and CRES reactions were relieved within one week after treatment. Hormone dosage was related to the duration of remission in patients, and the cumulative dose of methylprednisolone≥8 mg/kg showed a poor prognosis. CONCLUSION CAR-T is a safe and effective treatment for r/r B-ALL, most CRS and CRES reactions are reversible. BM blasts ≥36% before reinfusion and cumulative dose of methylprednisolone ≥8 mg/kg after reinfusion both affect the therapeutic effect. Ferritin≥2 500 ng/ml within two weeks after reinfusion is related to disease recurrence and is an independent prognostic risk factor.
Adolescent ; Antigens, CD19 ; Child ; Child, Preschool ; Chronic Disease ; Ferritins ; Humans ; Immunotherapy, Adoptive ; Methylprednisolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen/metabolism* ; Recurrence ; T-Lymphocytes

Objective: To understand the prevalence of HIV, hepatitis C virus (HCV) and syphilis and related factors among cross-border couples in Mangshi county, Dehong autonomous prefecture, Yunnan province. Methods: From May, 2017 to April, 2019, 2 500 couples with 5 000 cross-border marriages were selected by using cluster sampling method. The demographic characteristics, AIDS-related health services, HIV, HCV, syphilis infection and other information were collected through questionnaires and laboratory tests. The influencing factors of HIV, HCV and syphilis infection were analyzed by multivariate logistic regression model. Results: A total of 2 500 couples with cross-border marriage were investigated, among which 2 438 (97.5%) couples were Chinese men with Myanmar women. The average age of 5 000 participants was (34.16±9.00) years. Most of them were minority groups (59.9%), farmers (98.5%), education years ≤6 years (81.4%), marriage years>3 years (80.0%), and from mountainous areas (61.7%). The HIV prevalence of Chinese and Myanmar populations was 1.7% (43/2 500) and 2.0% (49/2 500), respectively. The HCV infection rates were 2.0% (49/2 500) and 1.3% (32/2 500), respectively and the infection rates of syphilis were 0.4% (10/2 500) and 0.2% (4/2 500), respectively. There were no statistically significant differences in the prevalence of three diseases among Chinese and Myanmar populations (P>0.05). The multivariate analysis showed that compared with those aged ≤ 30 years, having lower AIDS awareness, never receiving HIV testing, without HCV and syphilis infection, HIV prevalence was higher among those aged>30 years (OR=3.21, 95%CI: 1.80-5.73), having higher AIDS awareness (OR=17.41, 95%CI: 4.27-70.91), receiving HIV testing (OR=4.93, 95%CI: 2.72-8.92), with HCV infection (OR=5.64, 95%CI: 2.72-11.70) and syphilis infection (OR=8.37, 95%CI: 1.63-43.08). Compared with those aged ≤ 30 years, having marriage years ≤ 3 years, and with HIV negatives, HCV infection rate was higher among those age>30 years (OR=3.02, 95%CI: 1.69-5.38), having marriage years>3 years (OR=2.24, 95%CI: 1.34-3.74), and with HIV positives (OR=6.69, 95%CI: 3.29-13.59). Compared with those having HIV negatives, the syphilis infection rate was relatively higher among participants with HIV positives (OR=9.07, 95%CI: 2.00-41.10). Conclusion: The prevalence of HIV, HCV, and syphilis among cross-border couples in Mangshi county, Dehong autonomous prefecture of Yunnan province is relatively high. Age, AIDS awareness, HIV testing history, and the length of marriage are associated with the HIV, HCV, and syphilis infection.
Acquired Immunodeficiency Syndrome ; China/epidemiology* ; Female ; HIV Infections/epidemiology* ; Hepacivirus ; Hepatitis C/epidemiology* ; Humans ; Male ; Prevalence ; Risk Factors ; Syphilis/epidemiology*

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

Objective: High PM concentration is the main feature of increasing haze in developing states, but information on its microbial composition remains very limited. This study aimed to determine the composition of microbiota in PM in Guangzhou, a city located in the tropics in China. Methods: In Guangzhou, from March 5 to 10 , 2016, PM was collected in middle volume air samplers for 23 h daily. The 16S rDNA V4 region of the PM sample extracted DNA was investigated using high-throughput sequence. Results: Among the Guangzhou samples, , , , , and were the dominant microbiota accounting for more than 90% of the total microbiota, and was the dominant gram-negative bacteria, accounting for 21.30%-23.57%. We examined the difference in bacterial distribution of PM between Beijing and Guangzhou at the genus level; was found in both studies, but was only detected in Guangzhou. Conclusion In conclusion, the diversity and specificity of microbial components in Guangzhou PM were studied, which may provide a basis for future pathogenicity research in the tropics.
Air Microbiology ; Air Pollutants ; analysis ; Bacteria ; classification ; isolation & purification ; China ; Cities ; Environmental Monitoring ; Microbiota ; Particle Size ; Particulate Matter ; analysis ; RNA, Bacterial ; analysis ; RNA, Ribosomal, 16S ; analysis

Objective To characterize a species of the genus Tricula and parasitized trematodes in schistosomiasis-endemic areas of Yunnan Province using a molecular analysis, so as to understand their taxonomic positions. Methods Tricula spp. and Oncomelania snails were collected from Xiangyun County, Yunnan Province, and cercaria parasitizing snails were observed using crushing followed by microscopy. Cercaria parasitizing Tricula snails at various morphologies were sampled using a shedding method. Genomic DNA was extracted from snail soft tissues and cercariae, and the 16S rRNA, COI, 28S rDNA genes in snails and the ND1 and 28S rDNA genes in cercariae were amplified using a PCR assay and sequenced. The species of Tricula snails and their parasitized trematodes was characterized using sequence alignment and phylogenetic analysis. Results Among 382 Tricula snails detected, there were three types of trematode cercariae found, including the non-forked (20.94%, 80/382), double-forked (3.40%, 13/382) and swallow shapes (7.07%, 27/382). Sequence and phylogenetic analyses showed that the 16S rRNA, COI and 28S rDNA gene sequences of this species of Tricula had high homology to those in Delavaya dianchiensis, and were clustered in a branch. Sequencing analysis of the ND1 and 28S rDNA genes revealed that the non-forked cercariae belonged to the family Pleu- rogenidae, the swallow-shaped cercariae belonged to the family Opecoelidae, and the double-forked cercariae belonged to another species of the genus Schistosoma that was different from S. sinensium and S. ovuncatum. Conclusion The species and taxonomy of Triculla spp. and their parasitized trematodes are preliminarily determined in schistosomiasis-endemic areas of Yunnan Province; however, further studies are required to investigate the more definite taxonomy and pathogenicity.

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Salvage Therapy

BACKGROUNDAmyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders.

METHODSWe compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls.

RESULTSThe ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients.

CONCLUSIONSThe different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

Action Potentials ; Adult ; Aged ; Amyotrophic Lateral Sclerosis ; pathology ; physiopathology ; Diagnosis, Differential ; Female ; Hand ; pathology ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; physiopathology ; Muscular Atrophy ; pathology ; physiopathology ; Retrospective Studies ; Spinal Muscular Atrophies of Childhood ; pathology ; Spondylosis ; pathology

BACKGROUNDHirayama disease is a rare disease characterized by juvenile-onset of asymmetric amyotrophy, of which etiology has not been clarified. The aim of our study was to investigate the clinical and neurophysiologic characteristics of Hirayama disease.

METHODSNeurophysiological tests, including nerve conduction studies (NCS), F-wave and routine electromyography (EMG), were performed in seventy-three patients with Hirayama disease. EMG was selectively performed on upper and lower extremities, sternocleidomast and thoracic paravertebral muscles according to the clinical features of the patients.

RESULTSAbnormal NCS parameters, including decreased compound muscle action potentials or delayed distal motor latency, were found in 34.2% (25/73) and 12.3% (9/73) of the patients, respectively. A total of 24.6% (18/73) of the patients showed decreased F-wave frequency. EMG demonstrated the presence of neurogenic lesions in all patients with spontaneous potentials, prolonged duration or augmentation of amplitude in motor unit potentials (MUPs), or a single pattern of MUP recruitment. About 17.8% (13/73) of the patients showed neurogenic lesions, mostly in the C7-8 level of the cervical cord, only in the upper extremity of affected side, whereas 35.6% (26/73) of the patients possessed lesions in the upper extremities bilaterally. A total of 46.6% (34/73) of patients exhibited abnormalities in the lower extremities, sterno- cleidomast or thoracic paravertebral muscle. Changes in motor NCS were significantly correlated with muscle strength.

CONCLUSIONSEMG detects diffused subclinical neurogenic lesion in a high proportion of patients with Hirayama disease. Results of our study challenge the hypothesis that Hirayama disease is a type of cervical myelopathy.

Adolescent ; Adult ; Electromyography ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Conduction ; Spinal Muscular Atrophies of Childhood ; pathology ; physiopathology ; Young Adult

BACKGROUNDMyocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown.

METHODSA total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC.

RESULTSSTEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021).

CONCLUSIONSSTEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; pathology ; therapy ; Myocardial Reperfusion ; Myocardium ; metabolism ; pathology

This study was aimed to prepare the polyclonal antibody against the soluble proliferation-inducing ligand (sAPRIL) antigen and to investigate its effects in suppressing sAPRIL mediated lymphocyte proliferation. Mutated recombinant sAPRIL protein, which lacks biological activity but maintains immunogenicity, was used as antigen to immunize humanized SCID mice. Sera were obtained at 6 weeks after immunization. Indirect ELISA and Western blot were used to detect the antibody titer and specificity. The inhibition of polyclonal antibodies on Raji and Jurkat cell proliferation stimulated by sAPRIL was assessed by the MTT assay. The results showed that the mutant of sAPRIL could induce the production of polyclonal antibodies against human sAPRIL. Western blot and indirect ELISA analyses indicated that the anti-serum had higher specificity with a titer of 1:640. Functional analysis revealed that these polyclonal antibodies significantly inhibited the proliferation of Raji and Jurkat cell stimulated by sAPRIL (p < 0.05). It is concluded the polyclonal antibody against human sAPRIL is successfully prepared, which can inhibit the proliferation of Raji and Jurkat cells stimulated by sAPRIL in vitro.
Animals ; Antibodies ; genetics ; immunology ; pharmacology ; Antibody Specificity ; immunology ; Cell Proliferation ; drug effects ; Cloning, Molecular ; Humans ; Immune Sera ; analysis ; immunology ; Jurkat Cells ; Mice ; Tumor Necrosis Factor Ligand Superfamily Member 13 ; genetics ; immunology