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 investigate the efficacy of different treatment of oral lichen planus (OLP) patients with thyroid antibody positive and its correlation with thyroid antibody, providing more targeted treatment for OLP patients with thyroid antibody positive.Methods:Patients who were admitted to Department of Oral Medicine, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine for OLP with serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) from February 2020 to June 2024 were included. Demographic and clinical data were recorded, and qualitative status and quantitative titers of TPOAb/TGAb were collected. TPOAb and/or TGAb positive patients were included into the thyroid antibody positive group, while patients with both TPOAb and TGAb negative were included into the thyroid antibody negative group. According to the treatment methods, they were divided into topical treatment group, topical treatment combined with oral immunosuppressant group, and topical treatment combined with oral immunoenhancer group. After 2 weeks and 1 month of treatment, the clinical efficacy of thyroid antibody positive group and negative group in OLP patients under different treatment methods were compared, and the correlations of different clinical efficacy with age, sex and thyroid antibody titer were analyzed.Results:A total of 116 OLP patients were included in this study, of which 38 (32.8%) were thyroid antibody positive and 78 (67.2%) were thyroid antibody negative. Compared with untreated, the modified OLP score and pain degree in thyroid antibody negative group were significantly improved after 2 weeks and 1 month of topical treatment and topical treatment combined with oral immunosuppression ( P<0.01). Although the thyroid antibody positive group also showed a remission trend, there was no statistical significance before and after treatment ( P>0.05). For topical treatment combined with oral immunoenhancer, the modified OLP score and pain degree in both groups of antibody positive and negative were statistically significant different after 2 weeks and 1 month of treatment compared with before ( P<0.01), while there was no statistically significant difference between the two groups ( P>0.05). Multivariate Logistic regression analysis showed that the treatment efficacy of OLP in topical treatment group, topical treatment combined with oral immunosuppressant group, and topical treatment combined with oral immunoenhancer group had no significant correlation with age, sex, as well as the TPOAb and TGAb titer ( P>0.05). Conclusions:Thyroid antibody TPOAb and TGAb could be reference factors for the selection of OLP treatment plan. For patients of OLP with positive thyroid antibodies, topical therapy combined with oral immunoenhancers may be preferred.

Objective To investigate the effect of polymyxin B(PMB)combined with tigecycline(TGC)on delaying Klebsiella pneumoniae(KP)resistance to PMB,and to analyze the possible mechanisms involved in the induction and delay of resistance.Methods Six clinical isolates of KP strains from the Intensive Care Unit of First Affiliated Hospital of Army Medical University were subjected and then induced with PMB at 1/2 minimal inhibitory concentration(MIC)alone or combined with TGC at 1/2 and 1/4 MIC,respectively.The MIC changes of PMB in these strains were monitored over 14 consecutive passages.The strain 686K,which showed the most significant delay in resistance,was selected for further analysis.Differences in gene and protein expression were examined among the wild-type strain 686K,PMB-induced resistant strain(686K·R),and PMB combined with TGC delayed resistant strain(686K·DR)using transcriptome sequencing,qRT-PCR,and proteomics.Relevant target genes during the delay of resistance were analyzed through literature and bioinformatics analyses.Additionally,cpxR gene knockout strain 686K/ΔcpxR∷Apr and its complementation strain 686K/ΔcpxR∷Apr/pRK415-cpxR were constructed using homologous recombination technology to assess the expression levels of resistance-related genes and changes in MIC after induction in vitro.Results Under sub-MIC(1/2)PMB alone,resistance developed in all 6 KP strains within 2 d,while,the combination with TGC significantly delayed the development of resistance.Transcriptomic and proteomic analyses indicated that in strain 686K·R,the expression levels of the PhoP/Q two-component system,lipopolysaccharide(LPS)modification enzymes,and efflux pump systems were significantly up-regulated(|Log2FC|≥2,P<0.0001),while TGC co-administration markedly inhibited these expression changes.The cpxR deletion and complementation strains were successfully constructed.The expression levels of resistance-related genes phoP,pmrD,and acrA were decreased in the cpxR deletion strain(P<0.001),and the resistance was delayed until day 6 under PMB monotherapy,whereas the complementation strain restored the resistance phenotype by day 2.In the absence of cpxR,the effect of PMB when combined with TGC on delaying resistance did not differ from that observed with PMB monotherapy.Conclusion The combination of PMB and TGC can delay KP resistance to PMB.cpxR,as a critical regulatory factor,can impact PMB resistance by modulating LPS modifications and the expression of the AcrAB-TolC efflux pump,and plays an important regulatory role in the process of resistance induction.

Objective:To investigate the efficacy of different treatment of oral lichen planus (OLP) patients with thyroid antibody positive and its correlation with thyroid antibody, providing more targeted treatment for OLP patients with thyroid antibody positive.Methods:Patients who were admitted to Department of Oral Medicine, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine for OLP with serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) from February 2020 to June 2024 were included. Demographic and clinical data were recorded, and qualitative status and quantitative titers of TPOAb/TGAb were collected. TPOAb and/or TGAb positive patients were included into the thyroid antibody positive group, while patients with both TPOAb and TGAb negative were included into the thyroid antibody negative group. According to the treatment methods, they were divided into topical treatment group, topical treatment combined with oral immunosuppressant group, and topical treatment combined with oral immunoenhancer group. After 2 weeks and 1 month of treatment, the clinical efficacy of thyroid antibody positive group and negative group in OLP patients under different treatment methods were compared, and the correlations of different clinical efficacy with age, sex and thyroid antibody titer were analyzed.Results:A total of 116 OLP patients were included in this study, of which 38 (32.8%) were thyroid antibody positive and 78 (67.2%) were thyroid antibody negative. Compared with untreated, the modified OLP score and pain degree in thyroid antibody negative group were significantly improved after 2 weeks and 1 month of topical treatment and topical treatment combined with oral immunosuppression ( P<0.01). Although the thyroid antibody positive group also showed a remission trend, there was no statistical significance before and after treatment ( P>0.05). For topical treatment combined with oral immunoenhancer, the modified OLP score and pain degree in both groups of antibody positive and negative were statistically significant different after 2 weeks and 1 month of treatment compared with before ( P<0.01), while there was no statistically significant difference between the two groups ( P>0.05). Multivariate Logistic regression analysis showed that the treatment efficacy of OLP in topical treatment group, topical treatment combined with oral immunosuppressant group, and topical treatment combined with oral immunoenhancer group had no significant correlation with age, sex, as well as the TPOAb and TGAb titer ( P>0.05). Conclusions:Thyroid antibody TPOAb and TGAb could be reference factors for the selection of OLP treatment plan. For patients of OLP with positive thyroid antibodies, topical therapy combined with oral immunoenhancers may be preferred.

Objective To analyze the distribution characteristics of 9 hypertension drug related gene polymorphisms in the population of essential hypertension(EH)in Xi'an area,providing an objective basis for personalized treatment.Methods A total of 306 EH patients who visited the Shaanxi Provincial Armed Police Force Hospital from January 2022 to December 2023 were selected as the research subjects.The PCR melting curve method was used to detect 9 hypertension drug related gene polymorphisms,their genotype and allele distribution frequency were analyzed,and the correlations of gene polymorphism among patients of different genders,ages,and hypertension grading groups were compared.Results Among 306 patients,the distribution frequencies of each gene were consistent with Hardy Weinberg equilibrium(x2=0.153～2.941,all P＞0.05).Mutation rates of various gene were as follows:SLCO1B1 c.388A＞G,ADRB1 c.1165G＞C,MTHFR C677T,ADD1 c.1378G＞T,CYP2D6 c.100C＞T,ACE I/D,CYP3A5 c.806-4288C＞T,SLCO1B1 c.521T＞C,AGTR1 c.1166A＞C and CYP2C9 c.1075A＞C were 77.29％,73.20％,56.54％,48.37％,50.82％,35.13％,29.41％,11.76％,7.68％and 3.43％,respectively,and CYP2C9 c.403C＞T had no mutation.Comparing with patients of different genders,the mutation rate of SLCO1B1 c.388A＞G genotype and allele mutations in male group were higher than those in the female group(x2=5.221,8.237),the mutation rate of CYP2D6 c.100C＞T genotype and allele in the female group were higher than those in the male group(x2=5.093,9.661),the mutation rate of ACE I/D allele in the male group was higher than that in the female group(x2=6.118,8.032),with significant differences(all P＜0.05).The mutation rates of CYP2C9 c.1075A＞C,SLCO1B1 c.388A＞G,CYP2D6 c.100C＞T genotypes and alleles in the middle-aged and young age group were higher than those in the elderly group,and the differences were statistically significant(x2=11.683,10.243;9.003,9.803;10.617,9.931,all P＜0.05).There was no significant difference in the comparison of other genotypes and alleles among different gender and age groups and in the frequency of genotype and allele mutations among different hypertension grading groups(x2=1.321～7.733,1.031～5.198,all P＞0.05).Conclusion The distribution of gene polymorphisms related to antihypertensive drugs in the Xi'an area was related to the gender and age of EH patients.Thus,the genotype testing of antihypertensive drugs may have important guiding significance for personalized medication treatment of EH patients.

For the current lighting system for operating room,the manual adjustment of lighting position to eliminate shadow caused by obstruction will lead to distraction of surgeons'attention and potential contamination of the sterile environment in the surgical area.To address this issue,an intelligent dual-arm shadowless lamp system is proposed.A serial-type 5-degree-of-freedom dual-arm robotic system is adopted to construct the lighting system,and a D-H mathematical model is established to solve the forward and inverse kinematics of the robotic arms.For the clinical lighting scenarios of cross-focused illumination and master-slave supplementary illumination,the corresponding constraint mechanisms and motion planning methods are proposed for dual-arm cooperative control.Finally,a simulation analysis on the algorithm for the cooperative control of the dual-arm shadowless lamp system is conducted in MATLAB environment.The research results show that the dual-arm cooperative control algorithm is feasible and performs well,and that the motion trajectories of both the end effectors and joints of the arms are smooth and continuous,demonstrating that the intelligent dual-arm shadowless lamp system can meet the lighting adjustment requirements during operation.

Objective To explore the joint contact force, ligament tensile force and force transmission mode of foot internal structure in Down’s syndrome child (DSC) during standing. Methods The finite element models of foot were constructed based on CT image data from one DSC and one typically developing child (TDC). The models were validated by plantar pressure measurement during static standing. To simulate foot force during standing, the ground reaction force and the triceps surae force were applied as the loading condition. Contact pressure of the tibiotalar, talonavicular and calcaneocuboid joints, tensile force of the spring and plantar calcaneocuboid ligaments, and force transmission mode in transverse tarsal joints were calculated and analyzed. Results The finite element models of foot were validated to be reliable. Compared with the TDC, the DSC showed higher contact pressure at the tibiotalar joint and lower contact pressure at the talonavicular joint. The tensile force of spring and plantar calcaneocuboid ligaments of DSC was 10 times and 58 times of TDC, respectively. The forces transmitted through both mediate and lateral columns in DSC were lower than those in TDC. Conclusions Abnormal contact pressure of the tibiotalar joint, larger tensile force of midfoot ligaments and smaller force of the transverse tarsal joint were found in DSC during standing. The abnormal alteration of stress patterns in foot internal structure of DSC should be fully considered in clinical rehabilitation, so as to provide theoretical references for screening and making intervention plans for early rehabilitation, as well as designing individualized orthopedic insoles.

The purpose of this study is to analyze the biomechanics of ankle cartilage and ligaments during a typical Tai Chi movement-Brush Knee and Twist Step (BKTS). The kinematic and kinetic data were acquired in one experienced male Tai Chi practitioner while performing BKTS and in normal walking. The measured parameters were used as loading and boundary conditions for further finite element analysis. This study showed that the contact stress of the ankle joint during BKTS was generally less than that during walking. However, the maximum tensile force of the anterior talofibular ligament, the calcaneofibular ligament and the posterior talofibular ligament during BKTS was 130 N, 169 N and 89 N, respectively, while it was only 57 N, 119 N and 48 N during walking. Therefore, patients with arthritis of the ankle can properly practice Tai Chi. Practitioners with sprained lateral ligaments of the ankle joint were suggested to properly reduce the ankle movement range during BKTS.
Ankle ; Ankle Joint ; Biomechanical Phenomena ; Humans ; Knee Joint ; Lateral Ligament, Ankle ; Male ; Tai Ji

Objective:To investigate the clinical efficacy of percutaneous endoscopic lumbar discectomy (PELD) with the aid of neurophysiological monitoring under general anesthesia.Methods:From August 2016 to October 2019, 58 patients underwent PELD under general anesthesia were selected in our hospital; 30 were via transformational approach and 28 were via interlaminar approach. The whole operative procedures were performed under continuous monitoring of spontaneous electromyography (SEMG), and the peak value, waveform and motor unit of SEMG at the surgical side were observed. The clinical outcomes were evaluated by visual analogue scale (VAS) and Oswestry disability index (ODI).Results:PELD was successfully performed in all 58 patients. Abnormal SEMG reactions were recorded in 8 patients (13.8%), manifested as clustered or frequent high amplitude action potentials; 5 patients (16.7%, 5/30) were via transformational approach and 3 (10.7%, 3/28) were via interlaminar approach. Two patients relapsed at 3 and 6 weeks after surgery, respectively; one was treated with PELD again and the other one was treated with lumbar fusion and instrument fixation. The pain at the lumbago and leg was alleviated obviously after surgery in the 56 patients; the VAS scores were 7.43±1.32, 2.55±0.87 and 1.59±0.87 before surgery, and 3 d and 3 months after surgery, respectively, with significant differences ( P<0.05); the mean ODI before surgery and 3 months after surgery were 67.36±7.13 and 12.39±5.48, respectively, with significant difference ( P <0.05). Conclusion:PELD with the aid of neurophysiological monitoring under general anesthesia is safe and reliable, which can achieve good clinical efficacy.

Objective To explore the effects of individualized medical nutrition therapy on patients with end-stage renal disease receiving hemodialysis.Methods Totally 82 patients with end-stage renal disease who received hemodialysis in Beijing Rehabilitation Hospital of Capital Medical University between July 2015 and June 2017 were selected by convenient sampling and randomized divided into the control group (n=41) and the observation group (n=41) according to the treatment time. Patients in the control group received conventional nursing, while patients in the observation group received individualized medical nutrition therapy on this basis for three consecutive months. Nutritional status, quality of life and adverse effects were compared between the two groups.Results There was no significant difference in nutritional status and quality of life between the two groups before intervention (P>0.05). However, the observation group scored higher in body mass index (BMI), hemoglobin (HGB), plasma-albumin (Alb), creatinine (CRE) and quality of life than the control group post intervention (P<0.05), while its malnutrition-inflammation score (MIS) was lower than that of the control group (P<0.05). The incidence rate of adverse effects was lower in the observation group than in the control group (P<0.05).Conclusions Individualized medical nutrition therapy can effectively improve the nutritional status and quality of life, as well as reduce the incidence rate of adverse effects in the patients with end-stage renal disease who receive hemodialysis.