The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Codon optimization was performed for the M and HN genes of bovine parainfluenza virus type 3(BPIV3),and the recombinant shuttle plasmid Dual-M+HN was constructed.BPIV3 VLPs was prepared using the baculovirus expression system,and verified by Western blot,IFA and elec-tron microscopy.The successfully verified virus-like particle(VLPs)were mixed with MF59 adjuvant and CpG-ODN immunoenhancer to immunize mice by intramuscular-injection,and BPIV3 inactivated vaccine group and adjuvant control group were set up.The immune effect of BPIV3 VLPs was evaluated by monitoring mouse serum specific antibodies,neutralizing antibodies and hemagglutination inhibition antibodies.The results showed that the optimized codon adaptation in-dex(CAI)of the M and HN protein genes were 0.96 and 0.95,respectively,and the CG content reached 54.1％and 53.1％,respectively.The constructed recombinant plasmid was transformed in-to DHI0Bac for blue and white spot screening.The validated recombinant rod particles were trans-fected into Sf9 cells to obtain the rod-shaped virus pFastBac-M+HN.Under electron microscopy,BPIV3 VLPs with a diameter of approximately 180 nm were observed.IFA and Western blot ex-periments confirmed the successful expression and biological activity of the target protein.Through protein optimization,it was found that the protein expression was highest at an infection dose of MOI=5.After mixing 50 μg VLPs with MF59 adjuvant and CpG-ODN,mice were immunized by intramuscular injection.The results showed that the antibodies in the VLPs immunized group be-gan to rise at 2 weeks of the first immunization and reached their peak at 21 days of the second im-munization,with an average IgG antibody titer of 1∶40 228;The average titer of neutralizing anti-bodies is 1∶298;The titer of hemagglutination inhibition antibody is 1∶549,reaching the level of inactivated vaccine(P≥0.05),indicating that the VLPs prepared in this experiment can induce hu-moral immune response in the body.In summary,this study successfully prepared VLPs capable of self-assembly expression of BPIV3 HN and M proteins,and induced humoral immune response in mice,providing research basis for subsequent BPIV3 VLPs vaccine research.

The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Codon optimization was performed for the M and HN genes of bovine parainfluenza virus type 3(BPIV3),and the recombinant shuttle plasmid Dual-M+HN was constructed.BPIV3 VLPs was prepared using the baculovirus expression system,and verified by Western blot,IFA and elec-tron microscopy.The successfully verified virus-like particle(VLPs)were mixed with MF59 adjuvant and CpG-ODN immunoenhancer to immunize mice by intramuscular-injection,and BPIV3 inactivated vaccine group and adjuvant control group were set up.The immune effect of BPIV3 VLPs was evaluated by monitoring mouse serum specific antibodies,neutralizing antibodies and hemagglutination inhibition antibodies.The results showed that the optimized codon adaptation in-dex(CAI)of the M and HN protein genes were 0.96 and 0.95,respectively,and the CG content reached 54.1％and 53.1％,respectively.The constructed recombinant plasmid was transformed in-to DHI0Bac for blue and white spot screening.The validated recombinant rod particles were trans-fected into Sf9 cells to obtain the rod-shaped virus pFastBac-M+HN.Under electron microscopy,BPIV3 VLPs with a diameter of approximately 180 nm were observed.IFA and Western blot ex-periments confirmed the successful expression and biological activity of the target protein.Through protein optimization,it was found that the protein expression was highest at an infection dose of MOI=5.After mixing 50 μg VLPs with MF59 adjuvant and CpG-ODN,mice were immunized by intramuscular injection.The results showed that the antibodies in the VLPs immunized group be-gan to rise at 2 weeks of the first immunization and reached their peak at 21 days of the second im-munization,with an average IgG antibody titer of 1∶40 228;The average titer of neutralizing anti-bodies is 1∶298;The titer of hemagglutination inhibition antibody is 1∶549,reaching the level of inactivated vaccine(P≥0.05),indicating that the VLPs prepared in this experiment can induce hu-moral immune response in the body.In summary,this study successfully prepared VLPs capable of self-assembly expression of BPIV3 HN and M proteins,and induced humoral immune response in mice,providing research basis for subsequent BPIV3 VLPs vaccine research.

As a normal physiological substance,D-galactose can induce a process similar to natural brain aging in vivo and in vitro when administered excessively,and thus it is widely used to induce brain aging models in China and abroad.The model of brain failure induced by D-galactose has the advantages of a short modeling time,low cost,and significant effect.However,the induction mechanisms are complex and diverse,and the relationships between the mechanisms are unclear,which limit the practical applications of the model.This article reviews the in vivo metabolism of D-galactose and the various mechanisms involved in the induction of brain aging,as well as the links between the mechanisms,to provide a reference for the application and development of this model and the in-depth study of brain aging.

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

A retrospective analysis of the clinical data of seven acute B-lymphoblastic leukemia (B-ALL) patients with TCF3-HLF fusion gene-positive admitted to the First Affiliated Hospital of Soochow University from June 2017 to August 2022 was conducted to summarize their clinical features and prognoses. The seven B-ALL patients comprised four males and three females, with a median age of 18 (11-33) years. Five patients tested positive for CD33 expression, and four patients had a normal karyotype. Two patients had hypercalcemia at the initial diagnosis, and one patient developed hypercalcemia at relapse. Six patients presented with coagulation dysfunction at diagnosis. After induction chemotherapy, five out of seven patients achieved complete remission, of which four subsequently relapsed. Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy. Three patients underwent chimeric antigen receptor T cell therapy, whereas three patients subsequently underwent hematopoietic stem cell transplantation. Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

Objective To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. Methods A “admission-hospitalization-discharge” whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. Results The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = −7.688, −3.576 and −4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ² = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ² = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ² = 11.767, P < 0.01). Conclusions The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients’ cure.

Objective:To study the clinical effect of Microbotox in improving mandibular fat accumulation, lifting mandibular contour and achieving lower face and neck rejuvenation.Methods:From May 2020 to January 2021, patients with mandibular fat accumulation and skin relaxation of mandible and neck were treated in Plastic Surgery Hospital, Chinese Academy of Medical Sciences. Multiple microdroplets of botulinum toxin type A was injected into the dermis or the interface between the dermis and the superficial muscle layer in lower face and neck. Botulinum toxin was diluted to 20 U/ml and injected with 0.6 U per point. The scope of Microbotox was demarcated by the line between earlobe-mouth corner as the upper border, the depressor anguli oris as the anterior border, the front edge of sternocleidomastoid muscle front edge as the posterior border, and the jugular notch as the inferior border. Treatment effect was evaluated postoperatively by the subjective satisfaction of patients and the accessment of a third-party physicians.Results:A total of 25 patients were included, including 10 males and 15 females, with the age of 39.4±3.7 years. The patient subjective satisfaction was 96%(24/25), and 96%(24/25) of patients received improved result , evaluated by a third-party physician. There were no serious complications except one case of local congestion and four cases of local pain and swelling, which could be relieved in a short time.Conclusions:Characterized by improving mandibular fat accumulation, lifting mandibular contour, reducing cervicomental angle, improving skin texture and neck wrinkles, Microbotox is effective and practical.

Objective:To study the clinical effect of Microbotox in improving mandibular fat accumulation, lifting mandibular contour and achieving lower face and neck rejuvenation.Methods:From May 2020 to January 2021, patients with mandibular fat accumulation and skin relaxation of mandible and neck were treated in Plastic Surgery Hospital, Chinese Academy of Medical Sciences. Multiple microdroplets of botulinum toxin type A was injected into the dermis or the interface between the dermis and the superficial muscle layer in lower face and neck. Botulinum toxin was diluted to 20 U/ml and injected with 0.6 U per point. The scope of Microbotox was demarcated by the line between earlobe-mouth corner as the upper border, the depressor anguli oris as the anterior border, the front edge of sternocleidomastoid muscle front edge as the posterior border, and the jugular notch as the inferior border. Treatment effect was evaluated postoperatively by the subjective satisfaction of patients and the accessment of a third-party physicians.Results:A total of 25 patients were included, including 10 males and 15 females, with the age of 39.4±3.7 years. The patient subjective satisfaction was 96%(24/25), and 96%(24/25) of patients received improved result , evaluated by a third-party physician. There were no serious complications except one case of local congestion and four cases of local pain and swelling, which could be relieved in a short time.Conclusions:Characterized by improving mandibular fat accumulation, lifting mandibular contour, reducing cervicomental angle, improving skin texture and neck wrinkles, Microbotox is effective and practical.