Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

Cardiovascular disease has become the main cause of death worldwide,seriously threatening human life and health.Some studies have shown that cluster of differentiation 74(CD74)is involved in the pathology and inflammatory pathways of cardiovascular diseases,which has attracted wide attention from scholars.CD74 is a major histocompatibility complex(MHC)Ⅱ chaperone and macrophage migration inhibitory fac-tor(MIF)receptor.It activates a variety of signaling pathways and plays a biological role in the occurrence and progression of cardiovascular diseases.This article summarizes the relevant lit-erature advances of CD74 in cardiovascular diseases,to explore the pathogenesis from the perspective of CD74 and seek disease protection and more effective therapeutic targets.

Objective:To investigate the impact of vitamin D deficiency on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with polycystic ovary syndrome (PCOS) and normal ovarian reserve (NOR). Methods:A retrospective cohort study was conducted on infertile women undergoing their first IVF-ET cycle in the Department of Reproductive Genetics, Zhengzhou Maternity and Child Health Care Hospital from January 2018 to December 2023, including 318 PCOS patients (group P) and 528 NOR patients (group N). Each group was divided into three subgroups according to serum 25-hydroxyvitamin D [25(OH)D] levels: severe deficiency [25(OH)D<12 μg/L], deficiency [12 μg/L≤25(OH)D<20 μg/L], and non-deficiency [25(OH)D≥20 μg/L]. The impact of vitamin D deficiency on pregnancy outcomes was analyzed in each group. 1∶1 propensity score matching was applied to match the baseline characteristics between group P and group N , resulting in 158 matched cases of PCOS (group P) and NOR (group N). Pregnancy outcomes were compared between the two groups under the same vitamin D status.Results:1) Among PCOS patients, there were no significant differences in general characteristics and pregnancy outcomes among the three subgroups (all P>0.05). The two pronuclei (2PN) rate in the severe deficiency subgroup [59.93% (721/1 203)] was significantly lower than that in the deficiency subgroup [63.70% (1 032/1 620)], with a statistically significant difference ( P=0.045), and both were lower than that in the non-deficiency subgroup [68.06% (554/814)], with a statistically significant difference ( P<0.001, P=0.037). There were no statistically significant differences in the number of oocytes retrieved and MⅡ oocytes, MⅡ oocyte rate, 2PN number, 2PN rate, cleavage number, cleavage rate, number of available embryos on day 3 (day 3, D3), number of high-quality embryos on D3, D3 high-quality embryo rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, live birth rate, and premature birth rate among subgroups (all P>0.05). Female age ( OR=0.930, 95% CI: 0.871-0.992, P=0.028), endometrial thickness on the day of transfer ( OR=0.877, 95% CI: 0.791-0.971, P=0.012), number of D3 high-quality embryos ( OR=1.135, 95% CI: 1.050-1.228, P=0.001), and ovulation stimulating protocol ( OR=2.230, 95% CI: 1.153-4.314, P=0.017) were independent factors influencing clinical pregnancy. 2) Among NOR patients, there were no significant differences in general characteristics, pregnancy outcomes, laboratory parameters, or other outcome-related indices among the three subgroups (all P>0.05). Female age ( OR=0.944, 95% CI: 0.900-0.990, P=0.018), number of D3 high-quality embryos ( OR=1.070, 95% CI: 1.004-2.597, P=0.037), and number of transferred embryos ( OR=1.753, 95% CI: 1.184-2.597, P=0.005) were independent factors influencing clinical pregnancy. 3) After matching, there were no significant differences in baseline characteristics and pregnancy outcomes between group P and group N (all P>0.05). In the severe vitamin D deficiency state, group P had significantly lower MⅡ oocyte rate [76.64% (525/685)], 2PN rate [59.69% (345/578)], embryo implantation rate [35.71% (30/84)], and live birth rate [34.00% (17/50)] compared with group N [81.58% (465/570), P=0.033; 67.00% (335/500), P=0.013; 51.28% (40/78), P=0.046; 55.32% (26/47), P=0.035]. In the vitamin D deficiency state, the 2PN rate in group P [66.50% (532/800)] was significantly lower than that in group N [72.00% (725/1 007), P=0.012]. Conclusion:Vitamin D deficiency may adversely affect IVF-ET outcomes in patients with PCOS, with more pronounced effects in cases of severe deficiency. However, it has no impact on the assisted reproductive outcomes in NOR patients.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective:To investigate the effect of emergency whole course optimized management model based on first aid effect and blood gas index on the outcome and prognosis of patients with acute myocardial ischemia.Meth-ods:A total of 105 patients with acute myocardial ischemia admitted in People's Hospital of Hai'an City between May 2020 and January 2023 were enrolled in this randomized controlled study.Patients were divided into control group(n=53)and intervention group(n=52).Patients in the control group received routine emergency nursing mode,while those in the intervention group received whole course optimized management mode of emergency nurs-ing.Patients in both groups received a one-week nursing intervention.The indexes of emergency time,cardiac function,psychological condition,blood gas indexes and incidence of adverse events during nursing were compared between the two groups.Results:Compared to those in the control group,participants in the intervention group had significant lower triage assessment time[(0.59±0.22)min vs.(3.57±0.38)min,P＜0.001],time of the first ECG[(5.30±0.84)min vs.(9.58±1.02)min,P＜0.001],venous passage time[(6.22±1.27)min vs.(15.20±2.29)min,P＜0.001],anticoagulant administration time[(9.56±1.46)min vs.(16.23±2.17)min,P＜0.001],total emergency time[(52.50±2.99)min vs.(70.34±5.32)min,P＜0.001],significant higher partial pressure of oxygen in arterial blood(PaO2)[(78.24±3.25)mmHg vs.(70.20±3.02)mmHg,P＜0.001],and sig-nificant lower left ventricular end-diastolic diameter(LVEDd)[(52.27±4.37)mm vs.(57.86±5.59)mm,P＜0.001],left ventricular end-systolic diameter(LVESd)[(35.25±3.77)mm vs.(42.51±4.29)mm,P＜0.001],scores of self-rating anxiety scale(SAS)[(31.17±5.06)points vs.(48.62±5.60)points,P＜0.001],self-rating depression scale(SDS)[(32.19±4.78)points vs.(44.93±5.91)points,P＜0.001]and partial pres-sure of carbon dioxide in arterial blood(PaCO2)[(33.00±2.70)mmHg vs.(40.72±3.15)mmHg,P＜0.001].We detected lower adverse event occurrence(12.00％vs.28.00％)in the intervention group(P=0.046).Conclu-sion:The emergency whole course optimized management may reduce the time consuming of all aspects of emergen-cy,alleviate the anxiety and depression,improve blood gas indexes,and reduce the occurrence of adverse events in patients with acute myocardial ischemia.

Objective:To induce an experimental autoimmune encephalomyelitis(EAE)model by MOG-specific TCR trans-genic mice(2D2TCR transgenic mice),and to investigate effect of exogenous ERMAP on T cells in spleen of MOG35-55-induced 2D2TCR transgenic mice.Methods:EAE models were established in two groups of 2D2TCR transgenic mice(Control-Ig treatment for control group and ERMAP-Ig fusion protein treatment for experimental group),with 9 mice per group.Severity of spinal cord injury of MOG35-55-induced EAE in mice was assessed based on daily clinical scores(DAI),HE and LFB staining results;autoreactive T cells(CD4+Vα3.2+Vβ11+),T cell proliferation activation indicators CD69(CD4+Vα3.2+Vβ11+CD69+)and Ki67(CD4+Vα3.2+Vβ11+Ki67+),Treg(CD4+Vα3.2+Vβ11+CD25+Foxp3+)and Th17 cells(CD4+Vα3.2+Vβ11+IL-17A+)in spleen were detected by flow cytome-try;IL-17A,IL-6,IFN-γ and TGF-β expressions in spinal cord tissues were detected by qRT-PCR.Results:In MOG35-55-induced 2D2TCR transgenic mouse EAE model,ERMAP-Ig fusion protein treatment group showed milder inflammatory infiltration and demye-lination in spinal cord,decreased proportion of autoreactive T cells,decreased proportion of activated and proliferating T cells,increased proportion of Treg,inhibition of Th17 cell differentiation,less inflammatory cell aggregation and cytokine production,and increased expression of anti-inflammatory factors in spinal cord.Conclusion:ERMAP may be involved in development of EAE in 2D2TCR transgenic mice by inhibiting T cell proliferative activation and promoting Treg cell production.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the pregnancy outcomes and prognosis following in vitro fertilization,and tumor prognosis of infertility patients with borderline ovarian tumor(BOT)after fertility-sparing surgery(FSS).Methods A retrospective study was conducted and 35 infertility patients with BOT after FSS from Shanghai Jiai Genetics and IVF Institute,Obstetrics and Gynecology Hospital,Fudan University were enrolled.The pregnancy outcomes and tumor prognosis were analyzed.Results Among the patients,serous BOT accounted for 62.9％.Twenty-five cases were International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ,2 stage Ⅱ,and 8 stage Ⅲ.Twelve patients experienced borderline tumor recurrence before assisted reproductive therapy,of which 5 patients were stage Ⅲ and 7 stage Ⅰ.After FSS,the 35 patients firstly underwent controlled ovarian stimulation(COS)at an average interval of(47.3±32.6)months.A total of 79 ovulation induction cycles were taken and mild stimulation protocol was adopted first(41.8％),followed by the natural cycle protocol(25.3％).Twenty-seven patients underwent embryo transfer in 37 cycles,resulting in 21 clinical pregnancies in 19 patients.The clinical pregnancy rate was 56.8％,with a cumulative pregnancy rate of 54.3％.The live birth rate was 43.2％,and the cumulative live birth rate was 42.9％.For patients with anti-Müllerian hormone levels<1.0 ng/mL(n=13),the pregnancy rate was 42.9％,and the cumulative clinical pregnancy rate was 23.1％.Among 30 patients,4(13.3％)patient with stage Ⅲ BOT experienced recurrence,and none had malignant transformation at the median follow-up period of 61 months after the first COS.Conclusion Assisted reproductive technology was safe and could improve pregnancy rates in infertile women with BOT.

Cardiovascular disease has become the main cause of death worldwide,seriously threatening human life and health.Some studies have shown that cluster of differentiation 74(CD74)is involved in the pathology and inflammatory pathways of cardiovascular diseases,which has attracted wide attention from scholars.CD74 is a major histocompatibility complex(MHC)Ⅱ chaperone and macrophage migration inhibitory fac-tor(MIF)receptor.It activates a variety of signaling pathways and plays a biological role in the occurrence and progression of cardiovascular diseases.This article summarizes the relevant lit-erature advances of CD74 in cardiovascular diseases,to explore the pathogenesis from the perspective of CD74 and seek disease protection and more effective therapeutic targets.