ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

As the largest cancer in the world, breast cancer has both benefits and risks from its diversified treatments. Shared decision-making can respect the patient's right to information and autonomy, consider their preferences and value orientations, and help patients obtain the most suitable treatment plan, it also can reduce their decision-making difficulties and improve their disease knowledge awareness and decision-making satisfaction. This paper reviews the definition of shared decision-making, the influencing factors, steps, tools and clinical effects of shared decision-making in the treatment decision-making of breast cancer patients, in order to provide reference for the research of shared decision-making in breast cancer patients in China.

Breast cancer has now become the most common malignancy in women globally. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the common adverse reactions in chemotherapy for breast cancer, and when severe, it can significantly impact the treatment outcomes and quality of life of patients. This article provides an overview of the incidence, influencing factors, assessment tools, and intervention strategies for CIPN in breast cancer patients, with the aim of offering a reference for healthcare professionals to enhance symptom management in breast cancer patients.

Cardiovascular dysfunction and reduced exercise capacity are common adverse effects of anti-cancer treatments, severely impacting the prognosis and quality of life of cancer patients. This review summarizes the intervention protocols and application effects of resistance training on cardiovascular function and/or exercise capacity in cancer patients. The aim is to provide a reference for the practice of exercise interventions targeting cardiovascular function and exercise capacity among cancer patients in China.

OBJECTIVE To explore the material basis and potential mechanism of Kazakh classic prescription Wuzdekh （WZDK） in the treatment of enteritis. METHODS LC-MS/MS technology was used to analyze the chemical components in WZDK. Through network pharmacology and molecular docking technology， the main chemical components of WZDK were screened and the target was predicted； therapeutic effect and target of WZDK on acute enteritis were verified through in vivo experiments. The acute enteritis model of mice was induced by dextran sulfate sodium salt； the general condition of the mice was observed during administration and the disease activity index （DAI） score was calculated； pathological changes of the intestine and mRNA expression of core target were validated by HE staining and quantitative real-time PCR. RESULTS A total of 316 chemical components were obtained by LC-MS/MS. The core targets of network pharmacological analysis mainly included interleukin 1β（IL- 1β）， protein kinase B1 （AKT1）， tumor protein p53 （TP53）， IL-6， tumor necrosis factor （TNF） and so on. The results of molecular docking showed that chemical components such as mairin， lappadilactone， costunolide and dehydrocostus lactone were stable in binding to the core target. The results of in vivo experiment showed that， compared with model group， high dose （5.00 g/kg） of WZDK could significantly reduce the DAI score （P＜0.05）， improve inflammatory cell infiltration and mucosal tissue damage of colon tissue， and significantly down-regulated mRNA expressions of IL-6， TNF-α， IL-1β and TP53 in colon tissue（P＜ 0.05 or P＜0.01）. CONCLUSIONS Chemical components of WZDK such as mairin， lappadilactone， costunolide and dehydrocostus lactone may play the role of improving the imbalance of local inflammatory factors in the intestine and repairing damage of colonic mucosal tissue by down-regulating mRNA expressions of TNF-α， IL-6， IL-1β and TP53 in colon tissue.

Objective:To evaluate the efficacy of 1-year subcutaneous immunotherapy (SCIT) with dust mites in polysensitized allergic rhinitis (AR) patients and to analyze the serological markers associated with clinical response.Methods:A retrospective analysis of data from 69 polysensitized AR patients who completed 1-year SCIT with dust mites from Oct 2020 to Mar 2022 in Shandong Provincial ENT Hospital was conducted. The median patient age was 21 years, including 41 males and 28 females. The changes in symptoms and serum IgE, IgG4 assessed before and after treatment were evaluated. The differences in serological markers between effective and ineffective groups were analyzed. Multivariate regression analysis was used to investigate the predictors of clinical response. SPSS 22.0 software was used for data processing.Results:After immunotherapy, there was a significant reduction in symptom scores and a substantial improvement in the quality of life of polysensitized AR patients (all P<0.001). Dust mite specific IgG4 (sIgG4) significantly increased and dust mite specific IgE (sIgE)/sIgG4 significantly decreased (all P<0.05). sIgE, total IgE (tIgE), sIgE/tIgE and sIgE/sIgG4 were significantly lower in ineffective group than those in effective group (all P<0.05). The clinical response of SCIT related only to dust mite sIgE ( r=0.29, P=0.036), and sIgE≥53.86 kU/L had the best sensitivity (77.78%) and specificity (57.89%) to predict effective SCIT in polysensitized AR patients. Conclusions:One-year dust mite SCIT is effective for polysensitized AR patients. Pre-treatment serum dust mite sIgE≥53.86 kU/L may play a role in predicting clinical response of dust mite SCIT in polysensitized AR patients.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Zinc oxide quantum dots (ZnO QDs) were synthesized by gel-sol method and employed as the transdermal aloesin (Alo) carriers. ZnO QDs were surface-functionalized with amino using aminopropyltriethoxysilane (APTES). Alo was covalently bonded on the surface of ZnO QDs via N,N'-carbonyldiimidazole to obtain Alo NPs, which were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA). TEM images showed that ZnO QDs were analogously sphere and monodisperse with a reasonably narrow size distribution, of which was around 4 nm. The size of Alo NPs increased to around 8 nm due to the surface modification. The intense bands at around 3 400 cm and 1 200 cm in the FTIR spectrum of Alo NPs from the vibration of -OH indicated the linkage of Alo on the surface of ZnO QDs. The results of TGA analysis showed that the mass ratio of ZnO QDs and Alo were 39.27% and 35.14%, respectively. The penetration of Alo NPs was much higher than raw Alo according to the passive penetration experiments with Franz-type diffusion cells instrument using full-thickness cavy skin, which manifested the improvement of the penetration for Alo delivered by ZnO QDs. The pH-controlled drug release behavior was investigated. At pH 7.4, only a small amount of Alo (1.45% ± 0.21%) had been released after 2 h. In contrast, as incubation at pH 5.0 of which pH was similar to endosomal environment, Alo was released very fast (87.63% ± 0.46% in 2 h) from Alo NPs, confirming that Alo NPs could response to the pH and realize the intracellular drug release. The inhibitory effect of Alo NPs on tyrosinase was in a dose dependent manner. When the concentration of Alo NPs was 12.5 μg/mL, the inhibition rate was up to 40.32% ± 1.57%. All the results show that the Alo NPs hold a great potential in transdermal tyrosinase inhibition.
Administration, Cutaneous ; Animals ; Chromones ; administration & dosage ; Drug Delivery Systems ; Glucosides ; administration & dosage ; Guinea Pigs ; Monophenol Monooxygenase ; metabolism ; Nanoparticles ; Quantum Dots ; Zinc Oxide

Objective: To explore the expression of CD45 in newly diagnosed multiple myeloma (MM) and its relationship with clinical efficacy and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD45 in 130 cases of newly diagnosed MM, comparing clinical efficacy and prognosis in CD45⁺/CD45^- groups. Results: ①The CD45⁺ group was 33 cases (25.38%) , and CD45^- group was 97 cases (74.62%) . ②The objective remission rate (ORR) of CD45⁺ and CD45^-group was 33.33% and 64.95%, respectively. The difference was statistically significant (P=0.002) . For patients in Bortezomib regimen, the ORR of CD45⁺ and CD45^- group was 35.71% and 66.25%, respectively. The difference was statistically significant (P=0.005) . ③The median progress free survival (PFS) of CD45⁺ group and CD45^- group was 29.8 (95%CI 10.0-59.0) months vs 34.5 (95%CI 6.0-69.0) months (χ²=14.59, P<0.001) and the median overall survival (OS) was 32.5 (95%CI 10.0-68.0) months vs 37.6 (95%CI 6.0-78.0) months (χ²=11.42, P=0.001) , respectively. Among the patients in bortezomib regimen, The median PFS and median OS of CD45 ⁺ group and CD45^- group were 30.3 (95%CI 10.0-59.0) months vs 36.3 (95%CI 6.0-69.0) months (χ²=14.75, P=0.001) and 34.0 (95%CI 10.0-68.0) months vs 39.5 (95%CI 6.0-78.0) months (χ²=10.62, P=0.001) . ④Cox risk regression model analysis showed that serum creatinine≥176.8 μmol/L (HR=5.078, 95%CI 1.744-14.723, P=0.001) , CD45 positive (HR=14.504, 95%CI 0.168-0.42, P=0.001) , LDH≥220 IU/L (HR=1.308, 95%CI 1.16-2.417, P=0.015) were independent risk prognostic factors. Conclusion CD45 expression is a risk prognostic factor of MM patients. Bortezomib did not improve the poor prognosis of CD45⁺ MM patients.