Objective: To evaluate the effect and safety of neoadjuvant chemotherapy combined with PA-MSHA injection for breast cancer patients. Methods: An open randomized controlled clinical trial was con-ducted. Fourty patients with breast cancer were randomly assigned to neoadjuvant chemotherapy group (the control group, n=20) and neoadjuvant chemotherapy combined with PA-MSHA injection group (the experi-ment group, n=20). The evaluation of therapeutic effect was carried out when the treatment was completed. Kamofsky score was recorded before and after therapy. Venous blood was drawn before and after therapy and immune function (IFN-γ, IL-2, IL-4, and IL-10) and other indicators (Caspase-3, VEGF, MMP-2 and MMP-9) were measured by double antibody ELISA test. Adverse effects of PA-MSHA during therapy were ob-served and recorded. Results: The overall response rate (RR) in the experiment group was significantly higher than that in the control group (P<0.05). No significant difference was found in the pathologic complete remis-sion (pCR) between the experiment group and the control group (P>0.05). In the experimental group, pCR was significantly different before and after therapy (P<0.01). The score in the experimental group was signifi-cantly higher than that in the control group after therapy (P<0.01). With the treatment of chemotherapy and PA-MSHA injection, IFN-γ and IL-2 levels were significantly higher while IL-4 and IL-10 levels were significant-ly lower in the experiment group (P<0.05). A significant increase in serum Caspase-3 and a significant de-crease in serum VEGF, MMP-2 and MMP-9 (P<0.05) after therapy were also observed in the experimental group. The level of serum MMP-9 was decreased significantly (P=<0.05) after therapy in the control group. Con-clusion: Neoadjuvant chemotherapy combined with PA-MSHA injection can significantly improve the RR of breast cancer patients, enhance their cellular immune function, induce the apoptosis and restrain the metasta-sis of breast cancer cells. The PA-MSHA has been proved to be an ideal supplementary therapy for breast cancer.

Hepatocellular carcinoma(HCC)is a highly lethal cancer with significant incidence and mortality rates.The study of the biological features of liver cancer cells is critical for the development of novel treatment strategies for HCC.While traditional cell culture techniques fail to provide information on the growth and diffusion of cells in a threedim-ensional space(3D),3D bioprinting technology provides a new method to study the functional characteristics of HCC cells.With the development of 3D cell culture technology,researches are largely focused on exploring the function and behavior of cells in a three-dimensional environment,particularly in complex tumor models like liver tumors that comprise intricate cellular tissues and blood vessels.This article discussed about the cellular functions that need to be studied in the 3D bioprinting environment of HCC and other tumor cells by reviewing the research progress of 3D bioprinting in HCC and various other cancer cell lines,aiming to help researchers replicate the in vivo growth environment of tumor cells more accurately,expand application scenarios,and further explore cancer treatment methods.In addition,3D bioprinting technology is considered a promising tool for drug development,providing a more clinically relevant model for the pharmacological study of anti-cancer drugs,better revealing the drug sensitivity and resistance of tumors,reducing the need for animal experiments,and providing more possibilities for precision medicine.

Spatial epidemiology and molecular epidemiology have been widely used in the studies of tuberculosis (TB),but each with limitations.Integration of the two methods provides new ideas and methods in TB research.All referenced articles are from CNKI,Wan Fang database,PubMed database and Web of Science database.Method of combining spatial epidemiology and molecular epidemiology has been widely used in determining the local epidemic strains of TB genotype,the transmission mechanism,risk factors of TB,drug-resistant TB,as well as evaluating the effectiveness of TB prevention and control measures.Application of the combined methods is of important significance in the studies of TB,thus worthy to be further introduced to researchers and disease prevention and control workers in this country.

Migraine is a common nervous system disease, which could seriously affect the quality of life. However, the medical treatment of migraine cannot meet the clinical needs at present. With the deepening of research, serotonin 1F receptor agonists and drugs targeting CGRP are more and more developed and marketed. In this paper, the mechanism of action, safety and efficacy, metabolic characteristics of these drugs were systematically evaluated to provide a more scientific basis for clinical prevention and treatment of migraine.

Postnatal heart maturation is the basis of normal cardiac function and provides critical insights into heart repair and regenerative medicine. While static snapshots of the maturing heart have provided much insight into its molecular signatures, few key events during postnatal cardiomyocyte maturation have been uncovered. Here, we report that cardiomyocytes (CMs) experience epigenetic and transcriptional decline of cardiac gene expression immediately after birth, leading to a transition state of CMs at postnatal day 7 (P7) that was essential for CM subtype specification during heart maturation. Large-scale single-cell analysis and genetic lineage tracing confirm the presence of transition state CMs at P7 bridging immature state and mature states. Silencing of key transcription factor JUN in P1-hearts significantly repressed CM transition, resulting in perturbed CM subtype proportions and reduced cardiac function in mature hearts. In addition, transplantation of P7-CMs into infarcted hearts exhibited cardiac repair potential superior to P1-CMs. Collectively, our data uncover CM state transition as a key event in postnatal heart maturation, which not only provides insights into molecular foundations of heart maturation, but also opens an avenue for manipulation of cardiomyocyte fate in disease and regenerative medicine.
Gene Expression Regulation ; Heart ; Myocytes, Cardiac/metabolism* ; Single-Cell Analysis ; Transcription Factors/metabolism*

Background Per- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. Objective To analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. Methods Based on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable. Results Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). Conclusion Although differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.