Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

AIM: To explore the current status, research hotspots, and trends of global uveitis research to provide a theoretical basis and references for researchers in the field of uveitis, and promote further development in this area.METHODS: Relevant literatures on uveitis were retrieved from the China National Knowledge Infrastructure(CNKI)database, Wanfang database, and Web of Science core collection database since their establishment until 24 August 2023. The country/publishing institutions, research authors, high-frequency keywords, and burst keywords were visual analyzed by using software such as GraphPad Prism 9, CiteSpace 6.2. R2, and VOSviewer.RESULTS: Research teams for uveitis have been formed in various countries globally. The top three countries in terms of publications are the United States of America(7 585 papers), the United Kingdom(2 412 papers)and Germany(1 679 papers). The top three foreign institutions in terms of publications are Harvard University, Oregon Health & Science University, and Moorfields Eye Hospital, while the top three domestic institutions are Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Chongqing Medical University, and Zhongshan Ophthalmic Center, Sun Yat-sen University. The analysis of high-frequency keywords and burst keywords in Chinese and English shows that research hotspots mainly focus on exploring pathogenesis and different treatment methods for uveitis. The research hotspots related to uveitis treatment are transitioning to molecular biology-related research topics, such as molecular biological signaling pathways(NF-κB signaling pathway with a strength value of 22.89), biological agents(adalimumab with a strength value of 32.21), and tumor necrosis factor(with a strength value of 48.44). Related research is also expanding to basic experiments on relevant rats.CONCLUSIONS: In recent years, the research hotspots and trends of global uveitis mainly focus on precise diagnosis, pathogenesis, and more effective treatment methods. It is important for more scholars to dedicate themselves to uveitis-related research in the future to make breakthroughs and progress in the field. More large-scale and multicenter clinical studies on uveitis can provide high-quality research evidence.

Acute liver failure(ALF)is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people.Due to its high morbidity and mortality rates,unclear pathogenesis,and limited treatment methods,ALF has become a major problem that needs to be solved urgently in the field of liver diseases.In recent years,more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF,and the IRE1α/TRAF2/JNK pathway,as a part of endoplasmic reticulum stress signaling,plays a role in amplifying inflammatory response,promoting hepatocyte apoptosis,and inhibiting liver regeneration ability during the progression of diseases.As a traditional treasure of China,traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs.This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway,such as salidroside,Fructus Broussonetiae,Fructus Psoraleae+Schisandra chinensis,baicalein,genipin,kaempferol,resveratrol,sea buckthorn polysaccharide extract,and luteol,in order to provide a reference for further research and clinical practice of ALF.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Objective:To investigate the efficacy of hemodiafiltration combined with hemoperfusion in the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing maintenance hemodialysis (MHD).Methods:A total of 40 patients with SHPT undergoing MHD who received treatment at the Blood Purification Center of The First Affiliated Hospital of Anhui University of Science and Technology from February 2021 to March 2023 were included in this prospective cohort study. They were randomly divided into a control group and an observation group ( n = 20/group).The control group received a single high flux hemodialysis, while the observation group used a combination of hemodialysis filtration and hemoperfusion for 3 months. In both groups, the changes in hemoglobin, blood urea nitrogen, serum creatinine, serum calcium, serum phosphorus,and parathyroid hormone levels were compared before and after dialysis. Results:After dialysis, the hemoglobin level in the observation group was (119.45 ± 5.27) g/L, which was significantly higher than (106.30 ± 6.52) g/L in the control group ( t = -7.02, P < 0.001). The serum phosphorus level in the observation group was (1.18 ± 0.17) mmol/L, which was significantly lower than (1.52 ± 0.22) mmol/L in the control group ( t = 5.49, P < 0.001). The parathyroid hormone level in the observation group was (122.14 ± 40.57) ng/L, which was significantly lower than (168.78 ± 78.27) ng/L in the control group ( t = 2.39, P = 0.023). Conclusion:Hemodiafiltration combined with hemoperfusion can reduce clinical symptoms, increase hemoglobin level, and reduce phosphorus and parathyroid hormone levels in patients with SHPT undergoing MHD, which deserves clinical promotion.

Objective:To understand main problems existing in the construction of advanced stroke centers in China and put forward solutions, for reference in promoting the standardization construction of advanced stroke centers and improving the efficiency of acute stroke treatment.Methods:The data were derived from relevant data of on-site export guidance in the construction of advanced stroke centers at 175 tertiary hospitals from 2020 to 2021, and the scores of on-site evaluation indicators for the establishment of stroke centers and their formal approval were compared and analyzed. Based on on-site investigation and expert consultation, the common problems existing in the construction of advanced stroke centers were summarized. All data were analyzed by descriptive analysis, the scores of on-site evaluation indicators were expressed by ± s, and paired t test was used for comparison between groups. Results:Compared with the total score(693.04±72.06) of on-site evaluation at the stage of project launch, the total score(747.94±78.10) of on-site evaluation for formal approval of stroke centers of 70 hospitals was higher, and the difference was significant( P<0.01). There were seven common problems in the construction of stroke centers in 175 hospitals, including insufficient attention paid by hospitals, lack of effective performance incentive policies, imperfect treatment procedures and medical norms, and so on. Conclusions:Experts on-site guidance plays an important role in the construction of stroke centers in China. At present, there were still problems to tackle in the construction of stroke centers in hospitals. In order to promote the standardized construction of stroke centers in China and improve the efficiency of stroke treatment, the authors suggest fuorther strengthening the importance attached by hospital leadership and the coordination and organization of functional departments, establishing stroke center models conforming to the actual situation of the hospital, seting up the post of brain and heart health manager, and improving the regional prevention and treatment level of acute stroke.

Objective:To investigate the risk factors affecting the prognosis of patients with acute kidney injury (AKI) in the intensive care unit (ICU) based on the Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database, and to establish a prognostic model for AKI.Methods:Patients (aged ≥ 18 years) with acute renal failure, admitted to the ICU for the first time, and had complete hospital records (the RIFLE diagnostic criteria were used in the database, and the diagnosis was expressed as AKI in this article) were screened from MIMIC-Ⅲ database according to diagnostic codes. Patients were divided into two groups based on survival state at discharge, and the general information, underlying diseases, injury factors, vital signs and laboratory indicators within 24 hours after AKI, related intervention and prognostic indicators were analyzed. Univariate and multivariate Logistic regression analysis were used to determine the risk factors affecting mortality in patients with AKI and established a prediction model. The receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of the prediction model for the prognosis of AKI patients.Results:There were 4 554 patients with AKI included and 862 died, with mortality of 18.93%. Univariate Logistic regression analysis was performed for factors that might be associated with death in AKI patients, and the results showed that age, hypertension, lymphoma, metastatic carcinoma, vancomycin, aspirin, coagulation abnormalities, cardiac arrest, sepsis or septic shock, invasive mechanical ventilation, white blood cell count (WBC), platelet count (PLT), K +, blood urea nitrogen (BUN), total bilirubin (TBil), renal replacement therapy (RRT) and length of stay (LOS) were independent risk factors [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.002 (1.001-1.003), 0.764 (0.618-0.819), 1.749 (1.112-2.752), 2.606 (1.968-3.451), 1.779 (1.529-2.071), 0.689 (0.563-0.842), 1.871 (1.590-2.201), 2.468 (1.209-5.036), 2.610 (2.226-3.060), 2.154 (1.853-2.505), 1.105 (1.009-1.021), 0.998 (0.997-0.998), 1.132 (1.057-1.212), 1.008 (1.006-1.011), 1.061 (1.049-1.073), 2.142 (1.793-2.997), 0.805 (0.778-1.113), all P < 0.05]. Further binary Logistic regression analysis showed that lymphoma, metastatic cancer, vancomycin, cardiac arrest, sepsis or septic shock, coagulation dysfunction, invasive mechanical ventilation, increased BUN, increased TBil, increased or decreased blood K + and increased WBC were independent risk factors for death [β values were 0.636, 1.005, 0.207, 0.894, 0.787, 0.346, 0.686, 0.006, 0.051, 0.085, and 0.009; OR and 95% CI were 1.889 (1.177-3.031), 2.733 (2.027-3.683), 1.229 (1.040-1.453), 2.445 (1.165-5.133), 2.197 (1.850-2.610), 1.413 (1.183-1.689), 1.987 (1.688-2.338), 1.006 (1.003-1.009), 1.052 (1.039-1.065), 1.089 (1.008-1.176), and 1.009 (1.004-1.015), respectively, all P < 0.05]. The Hosmer-Lemeshow test showed that the AKI prognostic model was able to fit the observed data well ( P = 0.604). ROC curve analysis showed that the area under ROC curve (AUC) of the AKI prognostic model was 0.716 (95% CI was 0.697-0.735), when the cut-off value was 0.320, the sensitivity was 71.9%, the specificity was 60.1%, the positive likelihood ratio was 1.80, and the negative likelihood ratio was 0.47. Conclusion:The prognostic prediction model of AKI in critically ill patients established and based on the MIMIC-Ⅲ database may have practical significance for prognostic risk assessment of AKI and later intervention.

【Objective】 To investigate the effect of cold agglutination on blood group typing. 【Methods】 37℃ water bath, absorption elution test and 2-mercaptoethanol method were used to eliminate the influence of cold agglutination. Forward and reverse blood group typing, cross matching, DAT and IAT experiments were then performed on red blood cells and serum after treatment. 【Results】 Before treatment, obvious discrepancy in forward /reverse typing and nontypable cross matching in 16 blood samples were noticed due to cold agglutination. After corresponding treatments, all samples were consistent or negative in forward/reverse typing, cross matching and antibody screening. No adverse reactions to cross matching blood transfusion occurred in patients, and the increase of hemoglobin was in line with the effective standard of transfusion. 【Conclusion】 37℃ water bath, absorption elution test and 2-mercaptoethanol method can be used to eliminate the interference caused by cold agglutination to obtain correct typing results. The strong reactivity caused by cold agglutination in AIHA patients were different from other cases, which deserved our attention.