As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

Objective To investigate the relationship between prolactin and mild cognitive impairment(MCI)in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods A total of 319 postmenopausal women with T2DM who were hospitalized in the Department of Endocrinology,Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University were enrolled in this study from August 2016 to October 2023.All the patients were divided into two groups according whether they had MCI:T2DM group(n=161)and MCI group(n=158).Differences in clinical characteristics were compared between the two groups.Pearson correlation was used to analyze the correlation between sex hormones and cognitive domains,and Logistic regression analysis was used to evaluate the influencing factors for MCI development.Results Serum prolactin levels were significantly lower in the MCI group than in the T2DM group[(5.5±2.1)vs(7.2±2.9)μg/L,P<0.05].Serum prolactin level was positively correlated with mini-mental state examination score,Montreal cognitive assessment score,immediate memory score,visuopatial constructional score,attention score and hippocampal volume(P<0.05),and negatively correlated with processing speed test(time)and executive function test(time)(P<0.05).Logistic regression analysis demonstrated that serum prolactin level was an influencing factor for the risk of MCI in postmenopausal women with T2DM(OR 0.715,95%CI 0.605～0.845,P<0.01).Conclusions The decrease of serum prolactin level is associated with an increased risk of MCI in postmenopausal women with T2DM.

As a critical component of global agriculture,the dairy industry is essential for the food security and economic development.In China,the dairy sector in plateau regions plays an important role in addressing the nutritional needs of residents,boosting farmers' incomes,and fostering re-gional economic growth.However,the harsh high-altitude conditions,such as low oxygen,low at-mospheric pressure,and severe climate,pose significant challenges to the health and survival of dairy cows.This article summarizes the changes in physiological characteristics,metabolic perform-ance,production performance,and health status of dairy under high altitude areas,providing in-sights for the identification of adaptive traits in dairy to plateau.Also,the genetic and epigenetic mechanisms behind these phenotypic adaptations are discussed,and future directions and strategies for enhancing adaptability of dairy of dairy n plateau regions are outlined,thereby guiding re-searchers in adaptation evolution and breeding of dairy cattle.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Population aging in China has led to an increase in the incidence of abdominal aortic aneurysm(AAA).AAA rupture is one of the most severe life-threatening diseases,with high mortality.The main histopathological features of AAA include elastin degradation,smooth muscle cell depletion,extracellular matrix digestion,and mural leukocyte accumulation.Clinically,drug therapy is still lacking,and open/endovascular repair remains the most effective treatment strategy for AAA management.Notably however,the detailed molecular mechanism of AAA remains unclear,representing an important bottleneck affecting the development of potential drug targets.Animal models are the most powerful tools for clarifying the pathogenesis of AAA,and although some medium-to-large laboratory animal models(e.g.,rabbits,guinea pigs,dogs,pigs)have been established for AAA studies,rodent models(mice and rats)are still the main models used in this field.Current method of inducing AAA include intra-infrarenal aortic infusion of elastase,subcutaneous infusion of angiotensin Ⅱ,periaortic calcium chloride painting,and decellularized aortic xenografting;however,AAA tends to stabilize in most models after ceasing pre-induced stimulation(medical or surgical),and there remains a need for ideal animal models that maintain continuous aortic dilation and even rupture.AAA animal models are helpful for elucidating the pathogenesis of AAA,screening new drug targets,and promoting clinical translation.This review aims to discuss the application of current AAA modeling method and their translational relevance.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic bio-markers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the"masking"effect caused by high-abundance proteins.The relative abundance of middle-and low-abundance proteins increased substantially from 2.54％to 54.41％,and the top 20 high-abundance proteins decreased from 83.63％to 25.77％.Notably,our method can quantify approxi-mately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins iden-tified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Objective:To investigate the curative effects of Beck's cognitive therapy (BCT) combined with transcranial magnetic stimulation (TMS) on post-stroke sleep disorders in patients.Methods:A total of 120 patients with post-stroke sleep disorders who were diagnosed and treated in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine between January and December 2020 were included in this study. They were randomly assigned to undergo TMS (TMS group), BCT (BCT group), or TMS plus BCT (combined group) ( n = 40/group). Before and after treatment, sleep quality and mental state scores were evaluated in each group. Results:After treatment, the Pittsburgh Sleep Quality Index (PSQI) score in the combined group [(5.68 ± 0.33) points] was significantly lower than that in the TMS group [(9.11 ± 0.83) points] and BCT group [(11.37 ± 1.06) points, F = 512.63, P < 0.001]. Sleep efficiency in the combined group [(56.73 ± 2.62)%] was significantly higher than that in the TMS group [(39.55 ± 3.02)%] and BCT group [(35.23 ± 1.41)%, F = 863.59, P < 0.001]. The Self-Rating Anxiety Scale (SAS) scores and Self-Rating Depression Scale (SDS) scores were significantly lower in the combined group compared with the TMS and BCT groups ( F = 412.52, 310.60, both P < 0.001). Conclusion:BCT combined with TMS can effectively improve sleep quality and reduce negative emotions in patients with post-stroke sleep disorders.

ObjectiveA method was proposed for the determination of the concent of total glucoside of peaony(TGP) fromPaeonia lactifloriaPall. by UV spectrophotometry.MethodsBased on the extract with 80% acidities alcohol, extracted by aether and n-butyl alcohol, TGP was obtained fromPaeonialactifloriaPall.. The determination was established with paeoniflorin which was the main component of TGP as a contrast by UV spectrophotometry at 230 nm.ResultsA good liner relationship between concentrationof paeoniflorin and its absorbance was obtained,and the liner range was between 0.040 2~0.201 1 mg/ml. The averagerecovery was 101.81%.ConclusionThis method is simple rapid and reliable. It could be used for the semi-quantitative determination of TGP of paeony in paeonialactifloria pall..

Objective To investigate the incidence and clinical characteristics and look for assay or examination indexes or indicators with higher sensitivity and specificity of heart damage induced by exhaustive exercise in order to establish its preliminary clinical classification and diagnostic criteria. Methods In a military region for training staff,the clinical data of 88 soldiers who were admitted to the departments of cardiology in 6 general or central hospitals because of exhaustive exercise from January 2000 to December 2010 were analyzed. The myocardial enzyme, electrocardiogram(ECG),echocardiography and other related examination indexes or indicators were observed,and the changes of symptoms,signs and other relevant assay and examination indexes before and after treatment were recorded. Results Exhaustive exercise could cause the symptoms such as chest tightness,palpitations,chest pain, dizziness,shortness of breath,fatigue,syncope and other symptoms,as well as cardiac auscultation abnormalities. After treatment, aspartate aminotransferase〔AST(U/L):20.34±6.33 vs. 35.43±25.25〕,α-hydroxybutyrate dehydrogenase〔α-HBDH(U/L):130.47±9.04 vs. 168.93±62.69〕,lactate dehydrogenase〔LDH(μmol?s-1?L-1):2.48±0.62 vs. 3.58±1.34〕,creatine kinase〔CK(U/L):125.58±67.56 vs. 556.42±381.89〕,creatine kinase isoenzyme〔CK-MB(U/L):11.20±4.08 vs. 23.09±15.61〕were significantly lower than those before treatment(P<0.05 or P<0.01);cardiac troponin T(cTnT)was detected in 5 patients,its level after treatment was significantly lower than that before treatment(μg/L:0.07±0.05 vs. 1.26±0.78,P<0.05). The ECG abnormalities included primarily sinus bradycardia (16 cases),sinus arrhythmia (13 cases) and premature ventricular contractions (11 cases). Echocardiographic abnormalities appeared in 18 cases,they were chiefly as follows:valvular regurgitation, cardiac dysfunction,cardiac enlargement,etc,among which the most common one was valvular regurgitation(all the refluxes were of small amount). Based on the above clinical manifestations and examination results,the exhaustive cardiac injuries were preliminarily divided into common type(20 cases),arrhythmia type(56 cases),heart failure type(2 cases)and sudden death(10 cases). Conclusions The clinical manifestations of exhaustive heart damage may appear in different types. Abnormal changes of myocardial enzymes,ECG and echocardiography are the strong evidences for the damage. Clinicians should pay attention to its prevention and treatment.