The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

As an optional method for the treatment of hypospadias, free tube graft urethroplasty has been applied in some centers in recent years. It has the advantages of convenient urethra materials, high freedom of surgery, and satisfactory urine flow and appearance, but there are fewer reported cases and many complications. Therefore, it is recommended to be used cautiously. This paper summarizes the experience of 497 cases of free surgical surgery based on Buck fascia reconstruction, including key points such as full correction of penile lower curvature, no tension-free urethra, long-inclined plane anastomosis, and reliable coverage enhancement.

Objective:To observe the clinical effects and adverse reactions of meropenem in the treatment of severe lung infection. Methods:Totally 62 severe bacterial lung infection patients were randomly divided into two groups randomly. The patients in the con-trol group (31 cases ) were treated with cefoperazone / sulbactam 2-8 g in 100 ml 0. 9% sodium chloride injections,ivd,q12h, and the treatment group (31 cases ) was treated with meropenem 1 g in 100 ml 0. 9% sodium chloride injections,ivd,q8h. The treatment course was 14 days. The bacterial clearance rate, dual infection rate, clinical efficacy and adverse drug reactions of the two groups were observed and compared. Results:The bacterial clearance rate in the control group was 85. 2% and that in the treatment group was 92. 85% (P>0. 05). The incidence rate of dual infection in the treatment group (3. 6%) was significant lower than that in the control group (P<0. 05). The total effective rate in the treatment group (96. 77%) was significant higher than that in the control group ( P<0. 05). The adverse reactions of the two groups had no significant difference (P>0. 05). Conclusion:Meropenem is ef-fective in the treatment of severe bacterial lung infection. It can clear bacteria and reduce dual infection effectively, which shows better efficacy than cefoperazone / sulbactam.

Objective To develop a three-dimensional finite element model of atlantoaxial instability and compare the biomechanical properties of percutaneous anterior transarticular screw (ATS) and posterior transarticular screw (PTS) fixations.Methods A pathologic three-dimensional finite element model of atlantoaxial instability was developed from CT images of the upper cervical spine of volunteers with the aid of softwares,such as Mimics,Freeform,and Ansys.Percutaneous C1-2 ATS and PTS fixation modes were simulated and implanted to the model.Under the preload of 40 N and force moment of 1.5 Nm in anterior flexion,posterior extension,lateral bending,and axial rotation,biomechanical properties of the two fixation modes were compared.Results Under the four loading modalities,both fixation techniques provided maximal inhibition on C1-2 movement.The maximal stress for ATS was larger than that for PTS and maximal displacement for ATS was smaller than that for PTS.Conclusions Both ATS and PTS provide similar outlook and are effective to stabilize the atlantoaxial joint.Biomechanical performance of percutaneous C1-2 ATS is better than that of percutaneous C1-2 PTS.

Objective To explore the relationship of professional stress,social support and somatic symptoms of sub-health status of Ningbo normal senior school teachers. Methods 128 normal senior school teachers were selected and investigated by professional stress scale,social support scale and somatic symptoms of sub-health status scale, and canonical correlation analysis was used. Results The canonical correlation coefficient were 0.563, 0.471( P <0.01) with the existence of social support variable. The somatic symptoms of sub-health status would be greater with the rise of their professional stress and the decline of their social support. The canonical correlation coefficient was 0.497( P <0.01) with the elimination of social support variable. The factor loading of "examination pressure","professional burden" and "career expectation" in canonical variable ξ add to 0.801,0.855,0.726 respectively. The factor loading of "feeling of fatigue","sleep disorders" in canonical variable η add to 0.774,0.859 respectively. Conclusion The social support have adjustment function between the professional stress and somatic symptoms of sub-health status.

Objective To explore possible associations between host polymorphism of HLA classⅡgenotypes and advanced hepatosplenic schistosomiasis japonica.Methods 45 advanced schistosomiasis patients(experimental group) and 44 age,and sex,matched patients with chronic schistosomiasis(control group) from the same area were investigated for their HLA class II gene DRB genotypes by genotyping the alleles using microarray DNA chip.The correlation of allele frequencies to advanced hepatosplenic schistosomiasis was compared for the two groups.Results HLA,DRB1*04x exhibited markedly higher frequency in advanced patients than that in control group(P