B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Melanoma is characterized by high malignancy, ranking the third among skin malignancies, and is associated with lack of specific treatment options and poor prognosis. Therefore, the development of effective therapies for melanoma is imperative. A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier. In this study, we engineered a microneedle (MN) system that integrates chemotherapy, photothermal therapy (PTT), and targeted therapy to enhance anti-tumor efficacy while effectively penetrating the skin barrier. In vitro studies have demonstrated that the MN drug delivery system (DDS) can effectively penetrate the stratum corneum of the skin, deliver therapeutics to subcutaneous tumor sites, and establish a drug reservoir at these locations to exert anti-tumor effects. Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells, exhibiting enhanced cytotoxicity against them. In vivo pharmacological investigations revealed that the combination of PTT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects, achieving a tumor inhibition rate of up to 98.15%. This in situ DDS minimizes involvement with other organs, significantly reducing chemotherapy-related side effects. In summary, the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application potential by enhancing anti-tumor efficacy while minimizing adverse effects.

Objective:To discuss the optimal doping concentration of vanadium(V)and silicon(Si)co-doped TiO? coating(V-Si TiO?)formed on titanium surface by electrochemical treatment,to evaluate its antibacterial effect under visible light irradiation,and to clarify its visible light response mechanism.Methods:The medical pure titanium sheets were subjected to micro-arc oxidation followed by high-temperature calcination,and V-Si TiO2 coatings with different doping concentrations were prepared by adjusting the ratio of V to Si in the electrolyte.The experiment was divided into 1V:10Si(V5Si50)group,2V:10Si(V10Si50)group,and 3V:10Si(V15Si50)group;control group was set up(contains only bacterial culture medium).The optimal doping concentration was screened based on comprehensive evaluation of surface morphology,ion release,photocatalytic ability,and biocompatibility;cell counting kit-8(CCK-8)method was used to detect the proliferation activities and the survival rates of the cells in various group.Subsequently,the optimized coating was characterized and compared by scanning electron microscope(SEM),atomic force microscopy(AFM),digital eddy current coating thickness gauge,X-ray diffraction(XRD),X-ray photoelectron spectroscope(XPS),and ultraviolet-visible absorption spectroscopy(UV-vis).The experiment was divided into PT group(blank control),PEO group(no element doping),V10 group(V doping),Si50 group(Si doping),and V10Si50 group(2V:10Si).The ability of the coating materials to degrade methylene blue(MB)and generation of reactive oxygen species(ROS)under visible light were detected.For antibacterial experiments,Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli)were used.The colony counts on plates in various groups were recorded after visible light irradiation for 2 h and dark treatment for 2 h,respectively.The ROS levels were detected using 2',7'-dichlorofluorescein diacetate(DCFH-DA)ROS probe.ROS scavenging experiment was performed using the optimal doping concentration V10Si50 group,and the two kinds of bacteria were divided into blank control group,N-acetylcysteine(NAC)group,V10Si50 group,and NAC+V10Si50 group.The colony counts on plates in various groups were recorded after visible light irradiation for 2 h.Results:The V concentration of 0.01 mol·L?1 and Si concentration of 0.05 mol·L?1 in the electrolyte solution were the optimal doping concentrations for the V-Si TiO? coating.The SEM observation results showed that compared with V5Si50 group and V15Si50 group,the surface pore size of the coating material in V10Si50 group was significantly decreased(P<0.05),and the coating thickness was significantly increased(P<0.05);its crystal structure was mainly anatase type,and the MB degradation rate of the coating material in V10Si50 group after 9 h of visible light catalysis was significantly increased(P<0.05).Compared with control group,the cell proliferation activity and cell survival rate in V10Si50 group were significantly increased at 1,2,and 4 d of cell culture(P<0.05);at 2 and 4 d of cell culture,the cell proliferation activity and cell survival rate in V5Si50 group and V15Si50 group were significantly decreased(P<0.05).Compared with PT,PEO,and Si50 groups,the colony counts of two kinds of the bacteria in V10 group and V10Si50 group after visible light irradiation for 2 h were significantly decreased(P<0.05).Compared with PT group and PEO group,the ROS levels in two kinds of the bacteria in V10Si50 group after 2 h of irradiation were significantly increased(P<0.05).Compared with V10Si50 group,the colony counts of two kinds of the bacteria in NAC+V10Si50 group were significantly increased(P<0.05).Conclusion:A reasonably loaded V-Si TiO? coating material(V10Si50)was screened out,which maintained good biological activity and significantly enhanced the antibacterial effect under visible light irradiation.

OBJECTIVE To investigate the factors influencing the changes in purchasing quantity in the procurement varieties of the first batch of volume-based drug centralized procurement （hereinafter referred to as centralized procurement）. METHODS Using 25 procurement varieties of the “4+7” policy as research objects， the changes in purchasing quantity of procurement varieties were analyzed before and after the implementation of the “4+7” pilot， renewal and expansion policies. The influential factors were determined from the three levels of drugs， medical institutions and regions； and the multiple linear regression model was used to analyze the influential factors for the changes in the purchasing quantity of procurement varieties. RESULTS Before and after the implementation of the “4+7” pilot， renewal and expansion policies， the purchasing quantity increased by 52.1， －0.2， 85.8 ten thousand DDDs on average， compared with base period. During pilot， renewal and expansion period， DDDc decrease in procurement varieties was positively correlated with the increase in purchasing quantity （P＜0.01）. During the pilot and renewal period， the number of absolutely alternative varieties was positively correlated with the increase in purchasing quantity （P＜0.1）. During the pilot and expansion period， the number of alternative varieties to a certain extent was negatively correlated with the increase in purchasing quantity （P＜0.05）. During the renewal period， the increment of purchasing quantity in tertiary hospitals was smaller than that of primary medical institutions （P＜0.05）. CONCLUSIONS There is a relationship between the decline of DDDc and the changes in the purchasing quantity， that is， the more the drug price dropped， the more the purchasing quantity increased. The number of alternative varieties for centralized procurement will affect the changes in their purchasing quantity， but it is not always stable. With the implementation of the policy， the volume of primary medical institutions gradually exceeds that of tertiary institutions， indicating that the consumption of centralized purchased varieties is transferred to the primary medical institutions， and centralized procurement has promoted the implementation of the hierarchical diagnosis and treatment system.

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

Objective Using the concept of allostatic load(AL)to evaluate aging of male SD rats and the effectiveness of Zuogui Pill in naturally aging rats.Methods Naturally aging male SD rats were tested at the ages of 2,5,8,14,18,and 21 months.They were divided into an elderly control group,low-dose Zuogui Pill group,and high-dose Zuogui Pill group.Intervention with Zuogui Pill was trialed for 3 months.Blood samples were taken from the tails of rats each month,and the number of T lymphocytes and rate of apoptosis were measured by flow cytometry.Low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),25 hydroxyvitamin D(25-OH-D),corticosterone(CORT),C-reactive protein(CRP),and interleukin-6(IL-6)were detected in rat sera.By identifying the collinearity between indicators and professional considerations,LDL-c,TC,HDL-c,FFA,TG,CORT,IL-6,CRP,25-OH-D,CD3+T cell count,and CD3+T cell apoptosis rate were included in the AL scoring.The threshold for each indicator was established with data from 5-month-old rats,and the score was 1 point below or/and above the threshold.Results The serum levels of LDL-c,TG,TC,25-OH-D,CRP,and IL-6 of rats showed significant changes with age,although the patterns of change differed.The CD3+T lymphocyte count significantly decreased with age(P＜0.01),while the apoptosis rates of CD3+,CD4+,and CD8+T lymphocytes significantly increased with age(P＜0.01).Zuogui Pill significantly increased serum CORT levels in elderly rats(P＜0.01)and reduced the apoptosis rate of CD8+T lymphocytes(P＜0.05).The AL score began to increase in rats at 5 months of age and reached its peak in those of 18 months of age.Conclusions AL can better characterize the aging process compared to a single indicator.Zuogui Pill can improve the stress response ability of aging rats and alleviate immunosenescence.

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10^-3 g·kg^-1·（3 d）^-1］， Shenqi Yiliu prescription group （27 g·kg^-1·d^-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To investigate the efficacy of a machine learning model based on radiomics of brain lesions on T 2WI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD). Methods:Totally 223 MS and NMOSD patients who were treated from January 2009 to September 2018 in Beijing Tiantan Hospital Affiliated to Capital Medical University, Donghu Branch of the First Affiliated Hospital of Nanchang University, Tianjin Medical University General Hospital, and Xuanwu Hospital of Capital Medical University were analyzed retrospectively, and according to the proportion of 7∶3, 223 patients were completely randomly divided into training set (156 cases) and test set (67 cases). A total of 74 patients with MS and NMOSD who were treated in Huashan Hospital Affiliated to Fudan University and China-Japan Friendship Hospital of Jilin University from January 2009 to September 2018 and in Xianghu Branch of the First Affiliated Hospital of Nanchang University from March 2020 to September 2021 were collected as an independent external validation set. All patients underwent brain cross-sectional MR T 2WI, radiomics features were extracted from T 2WI, and features were selected by max-relevance and min-redundancy and least absolute shrinkage and selection operator algorithms. Then various machine learning classifier models (logistic regression, decision tree, AdaBoost, random forest or support vector machine) were constructed to differentiate MS from NMOSD. The area under curve (AUC) of receiver operating characteristics was used to evaluate the performance of each classifier model in the training set, test set and external validation set. Results:Based on multi-center T 2WI, a total of 11 radiomics features related to the discrimination between MS and NMOSD were extracted and classifier models were constructed. Among them, the random forest model had the best efficiency in distinguishing MS from NMOSD, and its AUC values for distinguishing MS from NMOSD in the training set, test set and external validation set were 1.000, 0.944 and 0.902, with specificity of 100%, 76.9% and 86.0%, and sensitivity of 100%, 92.1% and 79.7%, respectively. Conclusion:The random forest model based on the radiomic features of T 2WI of brain lesions can effectively distinguish MS from NMOSD.

Hepatocellular carcinoma cells interact with tumor microenvironment, and exhibits There are temporal and spatial heterogeneity of hepatocellular carcinoma which interacts with tumor microinvironment. In this paper, we summarized the characteristics of hepatocellular carcinoma heterogeneity, the mechanism of heterogeneity, and the impact of hepatocellular carcinoma heterogeneity on diagnosis and treatment, so as to provide a new thinking direction for the diagnosis and treatment of hepatocellular carcinoma.