BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To investigate the spatial distribution characteristics and correlation between the prevalence of dental fluorosis and the chemical elemental composition of drinking water sources in coal-fired fluorosis areas. Methods: Based on the survey data on the prevalence of dental fluorosis at CDC in Guizhou Province in 2022, 274 original surface drinking water sources were collected in typical coal-fired fluorosis areas, and fluoride (F), calcium (Ca), magnesium (Mg), aluminum (Al), titanium (Ti), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), barium (Ba), lead (Pb) 17 elements; apply Moran's I index, Getis-Ord Gi* hotspot analysis of the global spatial autocorrelation of chemical elements in drinking water and the degree of aggregation of each element on the local area, and correlation analysis with the prevalence of dental fluorosis in the region. Results: Except for Cu, Zn, and Cd, global spatial autocorrelation Moran's I was negative, and all other elements were positive. F, Ca, Al, Ti, As, Mo, Cd, and Cu elements showed high values of aggregation in the southeastern low-altitude area; Mg, Ba, Pb, Cr, Mn, and Fe elements were mainly aggregated in the central altitude terrain transition area, Zn and Se elements in water sources are significantly positively correlated with the prevalence of dental fluorosis (P<0.05). In contrast, F, Mg, Al, Ti, As, Mo, Cd, Ba, and Pb elements negatively correlate (P<0.05). Elements in the central region were high-high aggregation, as a hot spot aggregation area with high disease incidence, while F, Al, Mn, Mo, Cd, and Ba elements in the western region were low-low aggregation, as a cold spot aggregation area with a low incidence of fluorosis. Conclusions: The risk of population fluoride exposure in surface drinking water sources is shallow. However, the chemical element content of drinking water sources in coal-fired polluted endemic fluorosis areas has prominent spatial geographical distribution characteristics. There is a significant spatial aggregation effect with the prevalence of dental fluorosis, which may play a synergistic or antagonistic effect on the occurrence and prevalence of dental fluorosis.
Humans ; Drinking Water ; Prevalence ; Coal ; Fluorides/adverse effects* ; Cadmium ; Fluorosis, Dental/epidemiology* ; Lead ; Selenium ; Arsenic

Objectives: Hand, foot and mouth disease (HFMD) is a widespread infectious disease that causes a significant disease burden on society. To achieve early intervention and to prevent outbreaks of disease, we propose a novel warning model that can accurately predict the incidence of HFMD. Methods: We propose a spatial-temporal graph convolutional network (STGCN) that combines spatial factors for surrounding cities with historical incidence over a certain time period to predict the future occurrence of HFMD in Guangdong and Shandong between 2011 and 2019. The 2011-2018 data served as the training and verification set, while data from 2019 served as the prediction set. Six important parameters were selected and verified in this model and the deviation was displayed by the root mean square error and the mean absolute error. Results: As the first application using a STGCN for disease forecasting, we succeeded in accurately predicting the incidence of HFMD over a 12-week period at the prefecture level, especially for cities of significant concern. Conclusions This model provides a novel approach for infectious disease prediction and may help health administrative departments implement effective control measures up to 3 months in advance, which may significantly reduce the morbidity associated with HFMD in the future.
China/epidemiology* ; Cities/epidemiology* ; Data Visualization ; Disease Outbreaks/statistics & numerical data* ; Forecasting/methods* ; Hand, Foot and Mouth Disease/prevention & control* ; Humans ; Incidence ; Neural Networks, Computer ; Reproducibility of Results ; Spatio-Temporal Analysis ; Time Factors

OBJECTIVE To compare t he diff erences of the fingerprint and in vitro antioxidant activity between decoction pieces of Polygonum cuspidatum by integrated technology of habitat processing and processing （short for IPDP ）and traditional processing decoction pieces （short for TPDP ）. METHODS Ten batches of IPDP and ten batches of TPDP were prepared by integrated technology and traditional technology ，respectively. HPLC method was used to establish and compare the fingerprints of IPDP and TPDP. The scavenging rates of DPPH free radical ，ABTS free radical ，superoxide free radical and hydroxyl free radical and reducing activity of Fe 3+ were detected for IPDP and TPDP. In vitro antioxidant activities were compared between IPDP and TPDP. RESULTS There were 11 common peaks in the fingerprints of IPDP and TPDP ，among which 17 came from IPDP and 13 came from TPDP. The peak heights of peak 6（polydatin）and peak 15（emodin-8-O-β-D-glucoside）in IPDP were significantly higher than those in the TPDP ，and the peak heights of peak 13（resveratrol），peak 17（emodin）and peak 19（physcion）in the TPDP were significantly higher than those in the IPDP. The results of in vitro antioxidant test showed that IPDP and TPDP had a certain scavenging capacity on DPPH free radical ，ABTS free radical ，superoxide free radical and hydroxyl free radicals ，and also had a certain reducing capacity on Fe 3+. CONCLUSIONS The integrated processing technology of P. cuspidatum has a good retention effect on the glycosides in P. cuspidatum ，and the in vitro antioxidant activity of IPDP is stronger than that of TPDP.

OBJECTIVE: To observe the effect of bloodletting acupuncture at twelve -well points of hand on microcirculatory disturbance in mice with traumatic brain injury (TBI), and to explore the protective effect of bloodletting therapy on TBI. METHODS: Sixty clean adult male C57BL/6J mice were randomly divided into a sham-operation group, a model group and a treatment group, 20 mice in each group. The TBI model was established by using electronic controlled cerebral cortex impact instrument in the model group and the treatment group. The mice in the treatment group were treated with bloodletting acupuncture at bilateral "Shaoshang" (LU 11), "Shangyang" (LI 1), "Zhongchong" (PC 9), "Guanchong" (TE 1), "Shaochong" (HT 9) and "Shaoze" (SI 1) immediately after trauma. The mice in the sham-operation group only opened the bone window but did not receive the strike. The regional cerebral blood flow (rCBF) was monitored by laser speckle contrast analysis (LASCA) using a PeriCam PSI System before trauma, immediately after trauma and 1, 2, 12, 24, 48, 72 h after trauma. The brain water content was measured by wet-dry weight method 24 h after trauma. The severity of functional impairment at 2, 12, 24, 48 and 72 h after trauma was evaluated by modified neurological scale scores (mNSS). RESULTS: ① 2 h after trauma, the mNSS in the model group and treatment group were >7 points, suggesting the successful establishment of model; compared with the sham-operation group, the mNSS was increased significantly from 12 to 72 h after trauma in the model group ( all <0.01), but the mNSS in the treatment group was significantly lower than that in the model group from 2 to 24 h after trauma (<0.01, <0.05). ② Compared with the sham-operation group, rCBF in the model group was decreased significantly immediately after trauma (<0.01), and the rCBF in the model group was lower than that in the sham-operation group from 1 to 72 h after trauma ( all <0.01); rCBF in the treatment group began to rise and was significantly higher than that in the model group 1-2 h after trauma (<0.01); 12-48 h after trauma, the increasing of rCBF in the two groups tended to be gentle until 72 h after injury, and rCBF in the model group was decreased while that in the treatment group continued to rise and was higher than that in the model group (<0.01). ③ 24 h after trauma, the brain water content in the model group was significantly higher than that in the sham-operation group (<0.01), and brain water content in the treatment group was significantly lower than that in the model group (<0.01). CONCLUSION The bloodletting acupuncture at twelve -well points of hand could improve microcirculation disturbance, increase microcirculation perfusion, alleviate secondary brain edema and promote the recovery of nerve function in mice with TBI.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Bloodletting ; Brain Injuries, Traumatic ; therapy ; Male ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Random Allocation

Objective: Renal fibrosis is the most common manifestation of chronic kidney disease(CKD).Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it,there is an urgent need to identify novel therapies.Hydrogen sulfide(H2S)is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body.This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application.Data sources: Literature was collected from PubMed until February 2019,using the search terms including "Hydrogen sulfide,""Chronic kidney disease," "Renal interstitial fibrosis," "Kidney disease," "Inflammation factor," "Oxidative stress," "Epithelial-to-mesenchymal transition," "H2S donor,""Hypertensive kidney dysfunction,""Myofibroblasts,""Vascuar remodeling,""transforming growth factor(TGF)-beta/Smads signaling,"and "Sulfate potassium channels."Study selection: Literature was mainly derived from English articles or articles that could be obtained with English abstracts.Article type was not limited.References were also identified from the bibliographies of identified articles and the authors' files.Results: The experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress,inhibiting the activation of fibrosis-related cells and their cytokine expression,ameliorating vascular remodeling and high blood pressure,stimulating tubular cell regeneration,as well as reducing apoptosis,autophagy,and hypertrophy.Therefore,H2S represents an alternative or additional therapeutic approach for renal fibrosis.Conclusions: We postulate that H2S may delay the occurrence and progress of renal fibrosis,thus protecting renal function.Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.

Circular RNA(circRNA)is a type of noncoding RNA with tissue specificity and high stabil-ity, which forms a closed continuous loop and is abundantly expressed in tissue cells. According to re-cent research, the regulatory function of circRNA elucidating in the occurrence and development of dis-ease shows a potential for diagnosing clinical disease and revealing disease mechanism. This paper re-views the biological characteristics, analysis methods of circRNA and its research progress in clinical ap-plication as biomarker, and outlooks its application in the field of forensic medicine.

ObjectiveTo investigate the pathological characteristics, diagnosis, and differential diagnosis of embryonal rhabdomyosarcoma (ERMS) in the male reproductive system.

METHODSWe obtained the clinicopathological features, immunophenotypes, and electron microscopic findings of 11 male patients with ERMS in the reproductive system from 2000 to 2015, analyzed the data, and reviewed relevant literature.

RESULTSERMS developed in these patients at a median age of 17 (9－58) years, 3 cases in the testis, 4 in the scrotum, 1 in the epididymis, and 3 in the prostate. ERMS presented no clinical specificity, which made it difficult to be differentiated from inflammatory and other benign lesions. Microscopically, the tumor cells were arranged in a diffuse or fascicular distribution and mainly composed of short spindle-like, round, or irregularly shaped cells with nuclear hyperchromatism, the cytoplasm strongly eosinophilic, with differentiation of the striated muscle. Some of the cells were naively differentiated or tennis racket-shaped and some exhibited vacuolar degeneration in the cytoplasm. The nuclei were round or short spindle-shaped with visible nucleoli and mitoses. Immunohistochemically, the tumor cells were positive for Myogenin (5/6), Desmin (11/11), MyoD1 (8/9), and Myosin (1/2). Electron microscopy revealed early myofibrils in the cytoplasm of the tumor cells.

CONCLUSIONSERMS is a rare and highly malignant tumor characterized by local invasion and early metastasis and apt to develop in the reproductive system of young males. The diagnosis of the malignancy is mainly based on its histopathological and immunohistochemical manifestations, combined with electron microscopy when necessary. Early surgical resection in combination with radio- and chemotherapy is recommended for its treatment, which could reduce the recurrence of the tumor and improve the survival of the patients.

OBJECTIVESTo introduce a classification system of upper sacral segment and its significance based on the continuous pelvic axial computed tomography scan.

METHODSThe whole pelvis 2.0 mm thick axial scan images of 127 cases were observed, the sacroiliac screw channel of S1 were measured, according to the size of the transverse screw channel the upper sacral segment were classified. Such as transverse screw channel existed and in at least 4 layer scan images its width was > 7.3 mm, it was defined as sacral segment of the normal type. Such as transverse screw channel existed and its maximum width was 7.3 mm or less on scanning level, it was defined as a transitional. Such as transverse channel did not exist, or its width on all scanning level was 0 mm or less, it was defined as dysplastic. Various cases,percentage, and the average of the transverse screw channel were calculated.

RESULTSThere were 58 normal (45.7%),42 transitional (33.1%), and 27 dysplastic (21.2%) upper sacral segments with an averaged width of the tansverse screw channel of 13.9 mm, 5.2 mm, and 0.9 mm, respectively. Each specimen could be defined as one of the three types of upper sacral segment without exceptions.

CONCLUSIONIt is possible to insert a transverse iliosacral screw into a normal upper sacral segment when indicated because of the capacious transverse screw channel. The transverse iliosacral screw placement into the transitional and dysplastic upper sacral segments was contraindicated because of the limited or none transverse screw channel. The transitional upper sacral segment was superior to the dysplastic segment due to its starting point location restriction on the true lateral sacral view.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Density ; Bone Screws ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Pelvic Bones ; diagnostic imaging ; surgery ; Sacrum ; diagnostic imaging ; surgery ; Tomography, X-Ray Computed ; Young Adult