ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang （HYT） on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group， a model group， a euthyrox group （20 μg·kg^-1）， a HYT group （12.06 g·kg^-1）， a HYT without Sargassum （HYT-H） group （9.90 g·kg^-1）， a HYT without Glycyrrhizae Radix et Rhizoma （HYT-G） group （10.26 g·kg^-1）， a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma （HYT-HG） group （8.10 g·kg^-1）， and a Sargassum and Glycyrrhizae Radix et Rhizoma （HG） group （3.96 g·kg^-1）. The blank group was given deionized water by gavage， and the others were given propylthiouracil （PTU） to replicate the goiter pathological model. Euthyrox was taken as a positive control drug， and the rest of the Chinese medicine groups were given the corresponding decoction by gavage， the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， and the contents of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， reactive oxygen species （ROS） in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 （Keap1）， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group， the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues （P<0.05， P<0.01）， significantly reduced activities of SOD and GSH-Px in the liver （P<0.01）， significantly increased mRNA expression of Keap1 （P<0.01）， and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. Compared with the model group， the HYT group manifested significantly reduced serum levels of AST， ALT， and ALP （P<0.05， P<0.01）， significantly reduced contents of MDA and ROS in liver tissue （P<0.01）， significantly increased the activities of SOD and GSH-Px （P<0.01）， significantly decreased mRNA expressions of Keap1， p53， and Caspase-3 （P<0.01）， and significantly increased mRNA and protein expressions of Nrf2 and HO-1 （P<0.05， P<0.01）. ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020， Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats， and the effect is better than that of the HG group， the euthyrox group， and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.

Objective To assess the impact of ultrasound-guided fascia iliaca compartment block on major cardiovascular events and postoperative prognosis in patients with lower limb aortoiliac occlusive disease(ASO).Methods This study was a retrospective study including 353 patients with lower limb arterial reconstruction surgery for ASO at Xiamen Hospital Affiliated to Zhongshan Hospital of Fudan University from January 2018 to January 2022.Patients were divided into two groups based on different anesthesia:the group receiving ultrasound-guided fascia iliaca block combined with sciatic nerve block(Group B)and the group receiving monitored anesthesia care(MAC)(Group M).The primary outcome was the occurrence of major adverse cardiovascular events after lower limb arterial reconstruction surgery in ASO patients.The secondary outcomes included the incidence of non-cardiac postoperative myocardial injury,postoperative amputation,and other adverse reactions such as postoperative delirium,nausea,and vomiting as well as postoperative laboratory indicators.By using propensity score matching to balance baseline characteristics before surgery,the impact of different anesthesia methods on the occurrence of MACE and prognosis after surgery in ASO patients was analyzed.Results After propensity score matching,the incidence of MACE in Group B was lower compared with Group M(10%vs.3.4%,P=0.038);The incidence of MINS in Group B(33%vs.25%,P=0.200);The amputation rate of Group B(4.2%vs.3.4%,P＞0.99);The incidence of complications in Group B was(6.8%vs.4.2%,P=0.39);There was no statistically significant differ-ence in postoperative laboratory indicators between the two groups(P＞0.05).Multivariate analysis showed that nerve block(OR=0.25,95%CI:0.05～0.93),postoperative HBG(OR=0.95,95%CI:0.91～0.99)were in-dependent factors in reducing the incidence of MACE.Conclusion Ultrasound-guidance fascia iliaca compartment block and sciatic nerve block could reduce the risk of major adverse cardiovascular events in patients undergoing lower limb arterial revascularization surgery.

Objective To develop a Behavioral Decision-making Scale for Glycemic Management in pregnant women with gestational diabetes and to test its reliability and validity.Methods Based on the trans-theoretical model and behavioral decision theory,the test version of the scale was formed through literature review,semi-structured interview,brainstorming,2 rounds of expert consultation and cognitive interview.A total of 560 pregnant women with gestational diabetes mellitus were recruited from 10 hospitals in Quanzhou,Fujian Province by convenience sampling method from 21 July to November 2023.The data were divided into 2 parts by random number method for exploratory factor analysis and confirmatory factor analysis.Results The scale included 4 dimensions of"behavioral decision-making motivation""behavioral decision-making influencing factors""behavioral decision-making intention"and"behavioral decision-making effectiveness"with 34 items.The Cronbach's αcoefficient of the total scale was 0.971;the split-half reliability was 0.919;the test-retest reliability was 0.863;the content validity index of the scale was 0.853.The exploratory factor analysis extracted 4 common factors,and the cumulative variance contribution rate was 78.28％.The confirmatory factor analysis showed that the factor structure of the scale was stable.Conclusion The scale has ideal reliability and validity,which can be used to measure the level of glycemic management behavior decision-making of pregnant women with gestational diabetes mellitus.

The eating habits of children developed during infancy and toddlerhood is the foundation of their eating behaviors in later life, and have great influence on their nutritional status and health.Caregivers′ feeding practices affect children′s eating behaviors.Feeding practices are modifiable and can be used as an intervention.In recent years, responsive feeding practices have been extensively recommended.In order to expand knowledge of responsive feeding practices, and promote optimal feeding practices and children′s healthy eating behaviors, evidence about the associations between responsive feeding and infant and toddler′s eating behaviors was summarized in this paper.

By using Doppler sensor and pressure sensor, the cerebrovascular stroke detector can be used to measure the blood flow velocity and blood pressure of the carotid artery. In this study, a variety of signal conversion and isolation processing techniques are proposed for processing and feature extraction of the output signals from the sensors. Finally, effective signal output waveforms that can be used to evaluate the cerebrovascular hemodynamics index (CVHI) are obtained, and the sound signal outputs that can reflect the change characteristics of blood flow velocity and blood pressure signals are generated, which realizes the application functional requirements of the detector.
Blood Flow Velocity/physiology* ; Cerebrovascular Circulation/physiology* ; Hemodynamics/physiology* ; Humans ; Stroke ; Technology

Objective:To investigate the characteristics and cytotoxicity in vitro of the residual leukemia cells in the culture system that caused the accidental transfer of CD19 chimeric antigen receptor (CAR) into leukemia cells during the preparation of autologous CD19 CAR-T cells of relapsed/refractory B-cell acute lymphoblastic leukemia.Methods:①Peripheral blood mononuclear cells (PBMC) of 30 patients with relapsed/refractory B-cell acute lymphoblastic anemia (R/R B-ALL) who accepted CD19 CAR-T cell therapy and six healthy volunteers were collected. ②The residual leukemia cells were analyzed by flow cytometry in the system after the PBMCs of R/R B-ALL patients were sorted by CD3 magnetic beads. ③ CD3 + T cells from patients and healthy volunteers were transfected with CD19 CAR and CD22 CAR lentivirus to prepare CD19 CAR-T and CD22 CAR-T cells. ④The Nalm-6 cell line was resuscitated and the Nalm-6 cells with CD19 CAR lentivirus were transfected to prepare CD19 CAR-Nalm-6 cells. The patient's primary ALL cells were transfected with CD19 CAR lentivirus at the same time. ⑤The transfection rates were analyzed by flow cytometer, the cell proliferation was analyzed by the CCK-8 method, and the cell-killing activities were detected by the lactate dehydrogenase method. Results:① Among the 30 R/R B-ALL patients who received CD19 CAR-T cell therapy, two patients had 2.04% and 3.32% residual leukemia cells in CD3 + T cells. After 4 days in culture, the residual leukemia cells disappeared and could not be detected by a flow cytometer with prolonged cultivation in vitro. ② The proliferation of CD19 CAR-Nalm-6 cells was higher than that of the Nalm-6 cells. ③ The killing activity of the CD19 CAR-T cells on Nalm-6 cells was higher than that of the CD19 CAR-Nalm6 cells at a target ratio of 1∶1 on 24, 48, 72 h, respectively. The cytotoxicity of CD22 CAR-T cells on CD19 CAR-Nalm-6 cells was significantly higher than that of CD19 CAR-T cells. ④ The cytotoxicity of CD22 CAR-T alone on CD19 CAR-Nalm-6 cells was higher than that of CD19 CAR-T combined with CD22 CAR-T at the same target ratio. Conclusion:The residual leukemia cells in the culture system in the preparation of CD19 CAR-T cells may lead to the introduction of CD19 CAR into leukemia cells and results in the failure of the CD19 CAR-T cell therapy. Detecting the residual leukemia cells in the culture system via flow cytometry before transfection with CD19 CAR lentivirus is needed. Thus, CD22 CAR-T cell therapy could be used as one of the salvage treatments.

Objective:To observe the local reactions and efficacy of CD19 CAR-T therapy in recurrence/refractory B-cell non-Hodgkin's lymphoma (R/R NHL) patients with >7.5 cm lesions.Methods:32 R/R NHL patients with >7.5 cm lesions were enrolled and injected with CD19 CAR-T cells. Flow cytometry was used to detect and observe the amplification of CD19 CAR-T cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines in peripheral blood of patients. The side effects of CD19 CAR-T cell therapy included systemic side effects and local reactions of tumor. The local side effects were observed by Ultrasound, Computed tomography and Magnetic resonance imaging. Treatment options included glucocorticoid, interleukin-6 antibody and drainage of exudate. Overall response rate (ORR) and overall survival rate (OS) were observed.Results:①Among the 32 patients, CR (40.63%) , PR (31.25%) and ORR (71.88%) were 13, 10 and 23, respectively. ②In all 23 patients received ORR, 13 patients had grade 1-2 CRS, while 10 patients had grade 3-4 CRS. All the 9 patients in the SD+PD group had grade 1-2 CRS ( P=0.030) . ③A total of 15 patients with tumor local reactions, included 9 patients with CR, 5 patients with PR and 1 patient with SD. The local reactions of the tumor included that the diameter of the superficial lesions increased with redness, swelling and heat pain. The deep lesions presented abdominal pain, abdominal distension, suffocation and local pain, and burning of the tumor. The deep lesions were enlarged or accompanied by local edema. The local exudative lesions were found in the abdominal cavity and pleural cavity. ④ Peak proportion of CD19 CAR-T cells in ORR group was higher than that of in SD+PD group[16.8% (5.3%-48.2%) vs 2.9% (1.5%-5.7%) , z=-4.297, P<0.001]. The peak proportion of CD19 CAR-T cells in ORR group with local reactions was higher than that of in patients without local reactions [22.2% (10.5%-48.2%) vs 12.6% (5.3%-21.6%) , z=-3.213, P=0.001]. The peak proportion of CD19 CAR-T cells in multiple lesion group was higher than that of in single lesion group [35.8% (1.5%-48.2%) vs 16.8% (10.5%-18.5%) , z=-2.023, P=0.040]. ⑤Occurrence of local reactions and tumor shrinkage time were both delayed compared with systemic side effects. ⑥In the ORR group, the OS of patients with tumor local reactions was longer than that of patients without tumor local reactions, but there was no difference in the two groups (75% vs 34.6%, P=0.169) . Conclusions:CD19 CAR-T cell therapy in R/R NHL patients with >7.5 cm lesions might cause tumor local reactions later than systemic side effects.Clinicaltrial::ChiCTR1800018059

Objective:To evaluate the effects of glucocorticoids (dexamethasone and methylprednisolone) on the proliferation of CD19 Chimeric antigen receptor (CAR) modified T cells in vitro.Methods:Peripheral blood mononuclear cells from healthy volunteers were collected as T cells. CD19 CAR-T cells were prepared by CD3 magnetic beads sorting and CD19 CAR lentivirus transfection. The transfection rates and the proportion of CD19 CAR-T cells in the culture system were analyzed using a flow cytometer. The mean fluorescence intensity (MFI) of CD19 CAR-T cells was measured after staining with Carboxyfluorescein diacetate succinimidyl ester cell proliferation tracer fluorescent probe, Lactate dehydrogenase (LDH) cytotoxicity assay was used to detect the effects of different concentrations of glucocorticoid on the killing activity of B-cell tumor cell lines.Results:In this study, the CD19 CAR transfection rate of CD19 CAR-T cells was (51.34±5.28) %. The killing activities of different doses of methylprednisolone on Nalm6, Pfeiffer, and U2932 tumor cells were higher than that of dexamethasone at 24 h. The killing activities of 4 mg/mL methylprednisolone on Nalm6, Pfeiffer, and U2932 were higher than that of 0.75 mg/ml group, while the killing activity of 12 mg/ml methylprednisolone was lower than that of 2.25 mg/ml dexamethasone at 48 h. However, the killing activities of different doses of methylprednisolone on EHEB tumor cells were lower than those of different doses of dexamethasone at 24 and 48 h. The average MFI and proportion of CD19 CAR-T cells under different concentrations of glucocorticoid the proliferation inhibition of CD19 CAR-T cells by dexamethasone was higher than that of methylprednisolone. The proliferation inhibition of CD19 CAR-T cells of the two glucocorticoids in high concentration groups were more obvious than that in low concentration groups. When CD19 CAR-T cells were co-cultured with different tumor cells, the proportion and average MFI of CD19 CAR-T cells showed that the proliferation inhibition of dexamethasone was higher than that of methylprednisolone. The proliferation inhibition of CD19 CAR-T cells of the two glucocorticoids in high concentration groups was more obvious than that in low concentration groups.Conclusion:Dexamethasone inhibits the cell proliferation of CD19 CAR-T cells more than methylprednisolone during the targeting of different tumor cell lines. The inhibition effect of dexamethasone on the proliferation and amplification of CD19 CAR-T cells was greater than that of methylprednisolone during the targeting of CD19 CAR-T cells to different tumor cell lines. Moreover, the inhibition effect of the high dose group was more obvious.

Objective To investigate the immunophenotypic characteristics of potential leukemia cells transfected with CD19 antigen receptor( CAR) during CAR-T cell preparation. Methods Morphological chan-ges in CD19 CAR-transfected cells were observed under inverted microscope. The transfection rate and immuno-phenotype of transfected Nalm-6 cells were analyzed by flow cytometry. Secretion of cytokines in the culture sys-tem was detected by chemiluminescence. Results The transfection rate of Nalm-6 cells by CD19 CAR was (46. 50±3. 78) ％ and that of KG1a cells was (15. 70±1. 22) ％. CD19 CAR-transfected Nalm-6 cells prolifer-ated more rapidly than Nalm-6 cells ( P values on 0 d, 4 d, 7 d and 12 d were 6. 339, 3. 447, 0. 012 and 0. 009). In the culture of CD19 CAR-transfected Nalm-6 cells, cell aggregation and adhesion were observed and they gradually gathered into a group. The rate of CD19 expression was only 1. 19％ in the CD19 CAR-transfect-ed Nalm-6 cell culture system with the transfection rate of (46. 50±3. 78) ％. After increasing the proportion of Nalm-6 cells in the culture system, CD19 expression was gradually increased, while the expression of CD22 re-mained stable. CD19 expressed by Nalm-6 cells cultured in the supernatant of CD19 CAR-transfected Nalm-6 cell culture system was decreased gradually. The levels of IL-10 and TNF-αsecreted by CD19 CAR-transfected Nalm-6 cells were higher than those by Nalm-6 cells. Conclusions Results of the immunophenotypic analysis of CD19 CAR-transfected leukemia cells suggested that CD22 CAR-T cell therapy could be used as a rescue or combination therapy for CD19 CAR transfection into leukemia cells.