ObjectiveTo observe the effect of Astragali Radix combined with Angelicae Sinensis Radix on the activation of adventitial fibroblasts in the rabbit model of intimal hyperplasia and decipher the underlying mechanism. MethodClean white rabbits of the same number of males and females were selected. They were randomly assigned into a sham operation group， a model group， an Astragali Radix group （1 g·kg^-1）， an Angelicae Sinensis Radix group （1 g·kg^-1）， and Astragali Radix-Angelicae Sinensis Radix groups at the ratios of 1∶1 （Astragali Radix 1 g·kg^-1 + Angelicae Sinensis Radix 1 g·kg^-1）， 1∶5 （Astragali Radix 1 g·kg^-1 + Angelicae Sinensis Radix 5 g·kg^-1）， and 5∶1 （Astragali Radix 5 g·kg^-1 + Angelicae Sinensis Radix 1 g·kg^-1）， and an atorvastatin calcium group （5 mg·kg^-1）. The rabbit model of intimal hyperplasia was established by common carotid artery cannula combined with high-cholesterol diet. The sham operation group only underwent the separation operation and not the cannula. The sham operation group had been fed with normal diet and the other groups with high-cholesterol diet （2% cholesterol + 3% olive oil + 95% common diet） since the first day after operation. At the same time， drugs were administrated in corresponding groups， and the sham operation group and model group were administrated with distilled water （15 mL·kg^-1） for 28 days. At the end of the experiment， blood was collected from abdominal aorta， and the morphological changes of adventitia were observed by Masson staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in adventitia was detected by immunohistochemical method. The expression of adventitial fibroblast marker vimentin and myofibroblast marker α-smooth muscle actin （α-SMA）， which can reflect the activation of adventitial fibroblasts， was detected by immunofluorescence double staining. Western blot was employed to determine the protein levels of transforming growth factor-β₁ （TGF-β₁）， Smad2， and p-Smad2. ResultCompared with the normal group， the modeling caused adventitial hyperplasia and up-regulated the expression of TNF-α， IL-1β， α-SMA， Vimentin， TGF-β₁， Smad2， and phosphorylation（p）-Smad2 in the injured vessels （P<0.05， P<0.01）. Compared with the model group， Astragali Radix combined with Angelicae Sinensis Radix at the ratios of 1∶1 and 5∶1 alleviated the adventitial hyperplasia and down-regulated the expression of TNF-α， IL-1β， α-SMA， Vimentin， TGF-β₁， Smad2， and p-Smad2 （P<0.05， P<0.01）. ConclusionAstragali Radix combined with Angelicae Sinensis Radix， especially at the ratios of 1∶1 and 5∶1， can ameliorate the adventitial hyperplasia in the rabbit model of intimal hyperplasia by inhibiting the transformation of adventitial fibroblasts to myofibroblasts and reducing the local inflammation of blood vessels. The mechanism may be associated with the inhibition of TGF-β₁/Smad2 signaling pathway.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.

Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.

Hepatic fibrosis is a common pathological process in the development of various chronic liver diseases into liver cirrhosis. Based on current research findings, it is widely believed that the process of hepatic fibrosis is reversible, and effective treatment cannot only delay the development of hepatic fibrosis into liver cirrhosis, but also alleviate the degree of hepatic fibrosis. Therefore, the research on the treatment of hepatic fibrosis is of great clinical significance. The article reviews the recent research advances in the treatment of hepatic fibrosis.

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy.However,many challenges remain in extending its application toward the treatment of solid tumors.The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy.One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3).We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture.LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model,which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

AIM:To investigate the influence and mechanisms of human pancreatic cancer tumor microenvironments on T-cell immunoglobulin mucin-3 (TIM-3) expression and function of dendritic cells (DCs).METHODS:Tumor-infiltrating dendritic cells (TIDC) and para-carcinoma tissue DCs were isolated by Ficoll-Hypaque density centrifugation from trypsinized pancreatic carcinoma tissues, and the peripheral blood mononuclear cells were isolated from pancre-atic cancer patients or healthy people.The expression of TIM-3 on DCs was detected by flow cytometry.DCs isolated from healthy people peripheral blood mononuclear cells were induced by rhGM-CSF and IL-4.The expression of TIM-3 in the DCs treated with the culture supernatants of Capan-2, SW1990 and Panc-1 pancreatic cancer cells or human skin fibroblast (Hs27) cells for 48 h, and in the DCs treated with supernatants of Capan-2 cells, anti-VEGF-R2, anti-IL-10 and EP2 re-ceptor blocking peptide were evaluated by flow cytometry.The releases of IFN-βand IL-12 in the culture supernatants of DCs pretreated with monoclonal antibody ( mAb) to TIM-3 or DNase+RNase, followed by stimulation with apoptotic Ca-pan-2 cells, were detected by ELISA.RESULTS:DCs in tumor microenvironments had higher expression of TIM-3 than the DCs from para-carcinoma tissues and pancreatic cancer patient or healthy people peripheral blood ( P<0.01 ) .TIM-3 expression in the DCs treated with the culture supernatants of Capan-2, SW1990 and Panc-1 pancreatic cancer cells for 48 h was much higher than that in Hs27 cells (P<0.05).Treatment with a combination of anti-VEGF-R2, anti-IL-10 and EP2 receptor blocking peptide largely diminished the upregulation of TIM-3 on the DCs mediated by Capan-2 cell superna-tants (P<0.05).The concentrations of IFN-βand IL-12 in the DCs with high expression level of TIM-3 were lower than those in the DCs with low TIM-3 expression level.Treatment with mAb to TIM-3 resulted in much more IFN-βand IL-12 releases (P<0.01), but DNase+RNase made this effect disappear.CONCLUSION:TIM-3 serves as a negative regula-tor of DCs innate immune responses in the pancreatic cancer microenvironments.The secretion of soluble factors to tumor microenvironment by pancreatic cancer cells, including IL-10, VEGF and PGE2 , may contribute to the regulation of TIM-3 expression.

Objective To study the effects of Apelin on glucose toxicity and islet cells PDX-1 protein expression.Methods The islet β cell line NIT-1 cells were incubated in the medium containing different glucose concentrations(normal glucose concentration group 5.6 mmol/L,high glucose concentration group 16.7 mmol/L,extremely high glucose concentration group 33.3 mmol/L) and +/-Apelin-36 respectively for 3 d.Then the basic insulin secretion amount of islet cells and their secretion amount after glucose stimulation were detected.The intracellular insulin content and the PDX-1 protein and mRNA expression were detected.Results Compared with the normal glucose group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the high glucose group and extremely high glucose group were significantly decreased and PDX-1 protein expression was declined(P＜ 0.05);compared with non-adding Apelin group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the adding Apelin high glucose group and extremely high glucose group were significantly decreased and PDX-1 protein expression was decreased(P＜0.05);the insulin level in islet cells of 6 groups was positively correlated with PDX-1 protein expression and had no correlation with PDX-1 mRNA expression.Conclusion Apelin may participate in the glucose toxic effect by decreasing PDX-1 protein expression,causes the decrease of insulin secretion,thus plays a role in the pathogenesis of diabetes.

Objective To explore the meaning of midkine (MK) levels in serum in different development stage of acute leukemia,and to explore the relationship between MK and WT1.Methods The levels of the MK in serum of 86 cases of acute leukemia and 30 cases of normal people were detected by ELISA.Real-time quantitative PCR (RQ-PCR) method was used to determine the expression of WT1 at mRNA level in 15 AML patients.Results The MK level in serum in the new diagnosed group was higher than that in the complete remission group and the normal control group [7.52 (5.44,10.55) ng/ml vs 3.52 (1.56,5.20) ng/ml vs 2.44 (1.89,3.12) ng/ml].There' s no statistical difference between midkine level in new diagnosed acute B cell leukemia (B-ALL) group and acute myeloid leukemia (AML) group [7.88 (5.78,15.78) ng/ml vs 6.25 (4.59,16.33) ng/ml].The clear correlation was found between the level of serum MK and quantities of marrow WT1 gene (r =0.529,P =0.043).Conclusions The level of MK in serum of acute leukemia patients is increased at the time of new diagnosis and decreased at complete remission.ELISA may be a way to measure the status of AL.The location of MK gene is adjacent to WT1 gene and MK' s clinical significance is similar to WT1' s,furthermore,there is a clear correlation between MK in serum and WT1 of marrow in quantities.

OBJECTIVETo review the development of T follicular helper (TFH) cells and their role in systemic lupus erythematosus (SLE) pathogenesis, the effect of dendritic cells (DCs) on TFH cells in SLE, as well as the potential use of TFH cells as a new therapeutic target in clinical practice.

DATA SOURCESThe data used in this review were retrieved mainly from the PubMed database (1989-2013). The terms used in the literature search were "T follicular helper cells," "systemic lupus erythematosus," and "dendritic cells."

STUDY SELECTIONRelevant publications about the TFH cells development, the interaction between the TFH cells and the DCs, and the clinical applications of TFH cells were identified, retrieved, and reviewed.

RESULTSTFH cells, a novel distinct CD4+ T cell subset, are specialized in providing help to B cells in the formation of germinal centers (GCs) and long-term protective humoral immune responses. The development of TFH cells from naïve CD4+ T cell is a multistep process. As the pivot of immunoregulation, DCs are indispensable for TFH cells generation. In addition to receptor-ligand interactions between TFH cells and DCs, the cytokines secreted by DCs are also necessary for TFH cell generation. TFH cell dysregulation has been implicated in the development of SLE. More evidence from animal models of SLE and SLE patients suggests that TFH cells are necessary for pathogenic autoantibody production. Therefore, therapeutically targeting TFH cells can be a promising approach to treat antibody-mediated autoimmune diseases including SLE.

CONCLUSIONTFH cells play a critical role in the pathogenesis of SLE, making them attractive therapeutic targets in clinical practice.