Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe²⁺ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe²⁺ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
Ferroptosis/drug effects* ; Dental Pulp/drug effects* ; Animals ; Pulpitis/pathology* ; Rats ; Thymalfasin/pharmacology* ; Humans ; Male ; Thymosin/pharmacology* ; Disease Models, Animal ; Rats, Sprague-Dawley

Objective To analyze the correlation between inflammation,nutritional indicators and hy-poproteinemia in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Meth-ods The clinical data of patients with AECOPD admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2020 to September 2022 were ret-rospectively analyzed,and the patients were divided into the hypoproteinemia group(n=73)and the non-hy-poproteinemia group(n=141)according to whether the serum albumin(ALB)was lower than 35 g/L.The clinical data,inflammatory indicators and nutritional indicators of the two groups were compared,Spearman correlation analysis was performed,and binary logistic regression analysis was performed to analyze the influ-encing factors of patients with AECOPD complicated with hypoproteinemia.Results There were statistically significant differences in age,length of hospital stay,and body weight between the two groups(P＜0.05).There were no significant differences in gender,number of hospitalizations in the past 1 year,height,diabetes,hypertension and proportion of coronary heart disease(P＞0.05).Compared with the non-hypoproteinemia group,the hypoproteinemia group had longer hospital stays and higher levels of C-reactive protein,neutrophil/albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and systemic immunoinflammatory index(SII).The prognostic nutritional index(PNI),body mass index(BMI),hemoglo-bin and total protein levels were lower,and the difference was statistically significant(P＜0.05).Body weight,BMI,hemoglobin,total protein,PNI and AECOPD patients with hypoproteinemia were negatively cor-related(P＜0.05),while age,length of hospital stay,C-reactive protein,NAR,NLR,PLR,SII and AECOPD patients with hypoproteinemia were positively correlated(P＜0.05).Binary logistic regression analysis showed that PNI,SII and NLR were the influencing factors of hypoproteinemia in AECOPD patients.Conclusion In clinical practice,attention should be paid to and timely correction of hypoproteinemia in pa-tients with AECOPD,improvement of inflammatory indicators and nutritional status of patients,and preven-tion of acute exacerbation.

The functional health and stability of the oral and maxillofacial system is one of the basic goals of orth-odontic treatment.Currently,it is believed that,in general,the condyle is located in the center of the joint fossa when the mandible is in an intercuspal position(ICP)in healthy normal people.At this time,the function of the temporoman-dibular joint(TMJ)is stable.Due to orthodontic tooth movement and subsequent occlusal changes,patients with maloc-clusion may experience related remodeling of the temporomandibular joint,especially changes in the position of the con-dyle.The position of the mandibular condyle is traditionally evaluated using a condylar position indicator.However,this method lacks consistency in obtaining condylar position changes.In recent years,in the clinical application of orthodon-tic treatment,cone beam computed tomography(CBCT)has become the first choice for examination.CBCT can accurate-ly measure the interarticular space and determine changes in condylar position.This article reviews the CBCT assess-ment of condylar position and related research on condylar position changes in patients with malocclusion before and af-ter orthodontic treatment.The literature review results indicate that there are differences in the condylar position of pa-tients with different malocclusions,and the condylar position may also change before and after orthodontic treatment.With a lower radiation dose,CBCT has higher accuracy in evaluating the condylar position in patients with malocclu-sion who undergo orthodontic treatment,thus promoting further study of the mechanism of condylar position changes in patients with malocclusion in the future and providing more accurate and personalized guidance for patient treatment.

The full implementation of the dean's responsibility system under the leadership of the Party Committee trans-forms the hospital's Party Committee from its past role as the"political core"to the"leadership core".In the process of hospital management transformation,establishing a collaborative governance system between the Party and the government is key to imple-menting the dean's responsibility system under the leadership of the Party Committee.Taking the exploratory practices of Shenz-hen Hospital,Beijing University of Chinese Medicine(Longgang)as an example,this involves a comprehensive summary from improving decision-making mechanisms,leveraging the combat fortification role of Party branches and the exemplary role of Party members,and continuously expanding the service coverage of Party-building efforts.This discussion aims to explore effective im-plementation strategies for the dean's responsibility system under Party Committee leadership,to promote high-quality develop-ment of hospitals,and to provide meaningful references for the implementation of this system in public hospitals.

The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.

Objective     To analyze the echocardiographic characteristics of above grade 3+ mitral regurgitation (MR) patients by 3D transesophageal echocardiography (3D-TEE) in transcatheter edge-to-edge repair (TEER) and compare the intervention rate of TEER treatment in patients with different risk stratification. Methods     We retrospectively analyzed the clinical data of 91 patients with above grade 3+ MR in Anzhen Hospital between June 2021 and April 2022. There were 45 males and 46 females aged 66.5±15.9 years. According to pathogenesis, the patients were divided into different anatomical groups and risk stratification groups. There were 34 patients in a simple degenerative group (simple DMR group), 28 patietns in a complex disease group (Complex group), 14 patients in a simple ventricular  functional reflux group (simple VFMR group), 9 patients in a simple atrial functional reflux group (simple AFMR group), and 6 patients in a mixed functional reflux group (mixed FMR group). All patients were examined with a unified standard of transthoracic echocardiography (TTE) and 3D-TEE to compare the characteristic three-dimensional structural changes of the mitral valve in each group. According to the three partition strategy of preoperative anatomical evaluation of TEER, the risk stratification was conducted for the enrolled patients, which was divided into three regions from light to heavy: green area, yellow area, and red area. TEER treatment intervention rate of patients with different risk stratification was calculated. Results     Ant leaf angle and post leaf angle were negative in the simple DMR and Complex groups, and non-planar angle, prolapse height and prolapse volume were higher than those of the other groups (P=0.000). Ant leaf angle and post leaf angle were positive in the VFMR group and the mixed FMR group. Anterior and posterior (AP) diameter of valve ring (P=0.036), tenting height and tenting volume were higher than those of other groups (P=0.000).  AP diameter, tenting height and tenting volume were changed mildly in patients with simple AFMR. MR patients in red and yellow zone achieved a 28.1% TEER intervention rate. Conclusion     Standardized TTE and TEE examinations are crucial for the qualitative and quantitative diagnosis of MR in the echo core-lab. 3D-TEE mitral valve parameter can help determine the exact pathogenesis of MR and to improve the interventional rate of challenging MR patients.

ObjectiveTo investigate the prevalence of overweight or obesity in community patients with schizophrenia in Shanghai and to explore the related factors. MethodsStratified cluster sampling method was used and the general condition， physical examination and laboratory examination data of patients with schizophrenia who voluntarily participated in 2020 free health examination of National Basic Public Health Service were analyzed. ResultsA total of 3 200 patients were included into the study ，and the prevalence of overweight and obesity was 36.75% and 17.19%， respectively. Multivariate logistic regression analysis indicated that age between 40 and 60 （OR=1.333， 95%CI： 1.030‒1.724）， intake of first-generation antipsychotics （OR=1.413， 95%CI： 1.112‒1.796）， intake of second-generation antipsychotics （OR=1.573， 95%CI： 1.288‒1.921）， high-normal blood pressure （OR=1.549， 95%CI： 1.245‒1.927）， high-abnormal blood pressure （OR=2.824， 95%CI： 2.204‒3.619）， elevated ALT （OR=1.874， 95%CI： 1.386‒2.535）， elevated FBG （OR=1.270， 95%CI： 1.066‒1.513）， and elevated TG （OR=1.652， 95%CI： 1.335‒2.044） were the related factors that associated overweight or obesity in patients with schizophrenia. ConclusionOverweight and obesity are highly prevalent among community patients with schizophrenia in Shanghai. Age between 40 and 60， taking first-generation and second-generation antipsychotics， blood pressure higher than 120/80 mmHg， elevated ALT， elevated FBG， and elevated TG are associated with overweight or obesity in patients with schizophrenia. To provide personalized health guidance， medical staff in primary health care institutions should pay more attention to high-risk groups of overweight and obesity in schizophrenia patients at annual physical examination.

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.