In situ tumor vaccine has become an important strategy in cancer immunotherapy owing to its ability to induce immune responses locally and overcome tumor heterogeneity. However, the abnormal structure and mechanical properties of the tumor’s physical microenvironment significantly limit the efficiency of vaccine delivery and immune efficacy. In this review, the key factors in the tumor’s physical microenvironment, including solid pressure, interstitial fluid pressure, matrix stiffness, and tissue microstructure, are systematically discussed. Their obstructive roles in immune cell infiltration, antigen presentation, and immune activation are analyzed. The potential of approaches, such as radiotherapy, anti-angiogenic therapy, extracellular matrix degradation agents, nanomaterials, and hydrogel delivery platforms, in reshaping the tumor’s physical microenvironment is explored. This review aims to offer theoretical and practical guidance for optimizing in situ vaccine strategies through the regulation of the tumor’s physical microenvironment, ultimately advancing the precision and effectiveness of cancer immunotherapy.

Objective:To investigate the clinical characteristics of omphalocele, and to assess the risk factors associated with adverse outcomes.Methods:A retrospective cohort study was conducted. Clinical data of 224 patients diagnosed with omphalocele, who were hospitalized at Children′s Hospital, Zhejiang University School of Medicine from January 2013 to December 2022, were collected. Based on their discharge outcomes, the patients were classified into 2 groups: favorable outcomes and unfavorable outcomes. Chi-square test or continuity correction χ2 test or Fisher exact probability method, and Mann-Whitney U test were used for intergroup comparisons. Logistic regression analysis was performed to identify risk factors associated with adverse outcomes in omphalocele. Results:Among the 224 patients with omphalocele, 126 were male. A total of 208 patients (92.9%) had favorable outcomes, while 16 patients (7.1%) had unfavorable outcomes. In the unfavorable outcomes group, 14 patients had giant omphaloceles, while 100 patients had giant omphaloceles in the favorable outcomes group. The rates of herniation of more than two intra-abdominal organs in the hernial sac, congenital heart defects, patent ductus arteriosus, pulmonary hypertension, sepsis and infection of the hernial sac, were all higher in the unfavorable outcomes group compared to the favorable outcomes group (all P<0.05). Patients with unfavorable outcomes had longer mechanical ventilation time, duration of oxygen use, duration of parenteral nutrition, hospital stays, and higher rates of parenteral nutrition-associated cholestasis compared to those with favorable outcomes (all P<0.01). Multivariate Logistic regression analysis indicated that pulmonary hypertension ( OR=9.39, 95% CI 1.20-73.32), sepsis ( OR=8.59, 95% CI 1.32-55.86), and congenital heart defects ( OR=6.55, 95% CI 1.11-38.73) were all independent risk factors for adverse outcomes in omphalocele (all P<0.05). Conclusions:Infants with omphalocele are prone to complications such as cardiovascular malformations, infections, and pulmonary hypertension. Adverse outcomes in omphalocele are associated with pulmonary hypertension, sepsis, and congenital heart defects.

Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Objective To investigate the mechanism by which angiopoietin-like protein 8(ANGPTL8)regulates vascular smooth muscle cell(VSMCs)apoptosis.Methods An in vitro abdominal aortic aneurysm cell model was established by stimulating human VSMCs(HUSMCs)with angiotensin Ⅱ(AngⅡ).Stable ANGPTL8 knockdown and over-expression VSMC cell strains were generated using lentiviral transfection.TUNEL staining was used to de-tect apoptosis.Western blot analysis was performed to measure the protein expression of ANGPTL8,caspase9,caspase3,Bcl-2,Bax,p53,and PUMA,while RT-qPCR was used to assess mRNA expression of ANGPTL8,Bcl-2 and Bax.Results AngⅡ significantly induced ANGPTL8 expression in HVSMCs in a time-and dose-de-pendent manner(P＜0.05).ANGPTL8 knockdown significantly reduced the expression of apoptosis-related proteins caspase9,caspase3,and Bax,while increased the expression of the anti-apoptotic protein Bcl-2(P＜0.05).Con-versely,ANGPTL8 over-expression markedly induced HVSMCs apoptosis,which was significantly suppressed by treatment with the p53 pathway inhibitor pifithrin-α(PFT-α).Conclusions ANGPTL8 may promote VSMC apop-tosis by activation of p53 signaling pathway.

Objective:This study aimed to investigate the clinical characteristics of oral mucositis (OM) in patients with hematological diseases who received secondary allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed data on 58 patients with hematological diseases who underwent secondary allo-HSCT at the Peking University People’s Hospital from January 2018 to December 2023. The control group included 116 randomized patients after primary allo-HSCT during this period (1:2 ratio) with matched gender, age, and diagnosis. The incidence of OM and overall survival (OS) were compared between the two groups.Results:The secondary allo-HSCT and control groups reported 17 (29.31%) and 16 (13.79%) cases that developed OM ( P=0.014), whereas 10 (17.24%) and 7 (6.03%) developed grade ≥3 OM ( P=0.019). The median time for OM to occur was 4 days (1-9 days) and 5 days (1-10 days) posttransplantation in the secondary allo-HSCT and control groups, respectively. The multivariate analysis revealed that the use of whole-body radiation therapy as the main pretreatment regimen was an independent risk factor for OM occurrence ( P=0.019). Among patients with OM, an age of <55 years is a risk factor for developing grade 3-4 OM ( P=0.028). All patients who underwent the secondary allo-HSCT received granulocyte implantation. The median time of granulocyte implantation in 17 patients with OM was 14 days posttransplantation, whereas the median time of granulocyte implantation in patients without OM was 12 days posttransplantation. The difference was not statistically significant ( P=0.721). The presence of OM did not affect the occurrence of acute graft-versus-host disease ( P=0.938). No statistically significant difference was observed in the 2-year OS rate between patients with and without OM during the secondary allo-HSCT (51.9% vs 50.4%, P=0.943). No statistically significant difference was observed in the 2-year OS rate between patients with OM undergoing the secondary allo-HSCT and those undergoing the primary allo-HSCT (51.9% vs 81.3%, P=0.185) . Conclusions:The proportion of patients with concurrent OM was significantly increased in the secondary allo-HSCT, and the severity was more severe. Whether or not to merge OM does not affect granulocyte implantation, acute graft-versus-host disease incidence, and 2-year OS rate.

From January 1, 2013, to March 1, 2024, nine patients with hematological malignancies complicated by Gilbert’s syndrome in Peking University People’s Hospital underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients comprised seven male and two female cases, with a median age of 38 (13-60) years old. Among them, three cases were acute myeloid leukemia, three cases were acute lymphocytic leukemia, two cases were myelodysplastic syndrome, and one case was chronic myelomonocytic leukemia. None of the patients had viral hepatitis. Of the nine cases, seven cases received the Bu-Cy+ATG regimen, while the other two cases received the TBI-Cy+ATG regimen (Bu, busulfan; Cy, cyclophosphamide; ATG, antithymocyte immunoglobulin; and TBI, total body irradiation). All patients achieved neutrophil engraftment, and eight received platelet engraftment. The median total bilirubin level was 45.4 (22.5-71.2) μmol/L before transplantation and 22.0 (18.0-37.2) μmol/L on -1d of preconditioning. The total bilirubin level on +20d after the transplantation of eight patients decreased compared with the baseline level before transplantation. Moreover, one patient had a transient increase in the total bilirubin level on +5d after transplantation, which was considered to be attributed to the toxicity of Bu. No patients were complicated by hepatic veno-occlusive disease. The median follow-up time was 739 (42-2 491) days. During the follow-up period, one patient died of recurrence, and the remaining eight patients had disease-free survival events.

Objective To investigate the effects of Huangqin Qingrechubi Capsule(HQC)on inflammation and uric acid and lipid metabolism in rats with gouty arthritis(GA)and its mechanism.Methods SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline,colchicine and HQC at low,medium and high doses(n=10)by gavage for 7 days.Toe swelling of the rats was detected at 4,8,24,48 and 72 h after modeling,and synovial histological changes were observed with HE staining.Serum levels of interleukin-10(IL-10),IL-18,tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),adiponectin,leptin,resistin and visfatin were measured by ELISA,and the levels of high-density lipoprotein cholesterol(HDL-C),triglyceride(TG),total cholesterol(TC),and uric acid(BUA)were detected.RT-qPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog(PTEN),phosphatidylinositol-3-kinase(PI3K)and protein kinase B(AKT)and the protein expressions of PTEN,PI3K,p-PI3K,AKT and p-AKT.Results The rat models of GA showed obvious toe swelling,which reached the peak level at 48 h.HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia.The rat models showed significantly increased expressions of TNF-α,TGF-β1,IL-18,TC,TG,leptin,resistin and visfatin,BUA,p-PI3K,and p-AKT and lowered levels of IL-10,APN,HDL-C,and PTEN.Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models.Conclusion HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

Objective To investigate the effects of Huangqin Qingrechubi Capsule(HQC)on inflammation and uric acid and lipid metabolism in rats with gouty arthritis(GA)and its mechanism.Methods SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline,colchicine and HQC at low,medium and high doses(n=10)by gavage for 7 days.Toe swelling of the rats was detected at 4,8,24,48 and 72 h after modeling,and synovial histological changes were observed with HE staining.Serum levels of interleukin-10(IL-10),IL-18,tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),adiponectin,leptin,resistin and visfatin were measured by ELISA,and the levels of high-density lipoprotein cholesterol(HDL-C),triglyceride(TG),total cholesterol(TC),and uric acid(BUA)were detected.RT-qPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog(PTEN),phosphatidylinositol-3-kinase(PI3K)and protein kinase B(AKT)and the protein expressions of PTEN,PI3K,p-PI3K,AKT and p-AKT.Results The rat models of GA showed obvious toe swelling,which reached the peak level at 48 h.HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia.The rat models showed significantly increased expressions of TNF-α,TGF-β1,IL-18,TC,TG,leptin,resistin and visfatin,BUA,p-PI3K,and p-AKT and lowered levels of IL-10,APN,HDL-C,and PTEN.Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models.Conclusion HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

Objective:This study aimed to investigate the clinical characteristics of oral mucositis (OM) in patients with hematological diseases who received secondary allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed data on 58 patients with hematological diseases who underwent secondary allo-HSCT at the Peking University People’s Hospital from January 2018 to December 2023. The control group included 116 randomized patients after primary allo-HSCT during this period (1:2 ratio) with matched gender, age, and diagnosis. The incidence of OM and overall survival (OS) were compared between the two groups.Results:The secondary allo-HSCT and control groups reported 17 (29.31%) and 16 (13.79%) cases that developed OM ( P=0.014), whereas 10 (17.24%) and 7 (6.03%) developed grade ≥3 OM ( P=0.019). The median time for OM to occur was 4 days (1-9 days) and 5 days (1-10 days) posttransplantation in the secondary allo-HSCT and control groups, respectively. The multivariate analysis revealed that the use of whole-body radiation therapy as the main pretreatment regimen was an independent risk factor for OM occurrence ( P=0.019). Among patients with OM, an age of <55 years is a risk factor for developing grade 3-4 OM ( P=0.028). All patients who underwent the secondary allo-HSCT received granulocyte implantation. The median time of granulocyte implantation in 17 patients with OM was 14 days posttransplantation, whereas the median time of granulocyte implantation in patients without OM was 12 days posttransplantation. The difference was not statistically significant ( P=0.721). The presence of OM did not affect the occurrence of acute graft-versus-host disease ( P=0.938). No statistically significant difference was observed in the 2-year OS rate between patients with and without OM during the secondary allo-HSCT (51.9% vs 50.4%, P=0.943). No statistically significant difference was observed in the 2-year OS rate between patients with OM undergoing the secondary allo-HSCT and those undergoing the primary allo-HSCT (51.9% vs 81.3%, P=0.185) . Conclusions:The proportion of patients with concurrent OM was significantly increased in the secondary allo-HSCT, and the severity was more severe. Whether or not to merge OM does not affect granulocyte implantation, acute graft-versus-host disease incidence, and 2-year OS rate.