Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

BACKGROUND:The thin alveolar bone in the lower anterior region increases the risk of labial bone resorption when intruding the teeth with clear aligners.The effect of sagittal overcorrection design on the labiolingual control of mandibular anterior teeth intrusion has not been fully investigated. OBJECTIVE:To explore the effect of overcorrection on the changes in the displacement and stress of the mandibular anterior teeth,especially the cervical and apical regions. METHODS:Through a male volunteer cone-beam CT data,the three-dimensional reconstruction of the mandible and teeth was conducted in the MIMICS and GEOMAGIC software.Moreover,the models of periodontal ligaments,attachments,and appliances were created in the SOLIDWORKS software.First,the study was divided into canine intrusion group and incisor intrusion group.Then,the overcorrection(0°,1°,2°)was designed on the bilateral mandibular central and lateral incisors.A total of six models were established.The models were assembled and imported into the ANSYS software to analyze and calculate the displacement and stress level. RESULTS AND CONCLUSION:(1)In the canine intrusion group,canines intruded and tipped lingually while incisors extruded and tipped lingually.In the incisor intrusion group,canines extruded and tipped lingually while incisors intruded and tipped lingually.(2)Without overcorrection,the incisors necks moved lingually while apexes moved labially.With overcorrection,the incisors tended to be upright,followed by labial tilt.The least cervical and apical displacements were detected under 1° overcorrection.(3)With overcorrection,the incisal cervical stress concentration area shifted from labial to lingual in the canine intrusion group,whereas the stress concentration area shifted from lingual to labial in the incisor intrusion group.(4)The incisors tended to tilt lingually when intruding the mandibular anterior teeth with clear aligners.The sagittal overcorrection design was conductive to maintain the stable position of incisors.However,the amount of overcorrection should be moderate.Excessive overcorrection might increase the labial inclination tendencies of incisors.

T-cell immunoglobulin and mucin domain-containing molecule-3(Tim-3)is a member of the Tim family and has been a research hotspot in recent years.As a negative regulatory factor,Tim-3 exerts different effects by binding to different ligands.Tim-3 is expressed in various types of immune cells,such as natural killer cells,dendritic cells,and monocytes,and Tim-3 has a regulatory effect on the functions of these immune cells.In recent years,a large number of studies have shown that Tim-3 is closely associated with the development and progression of liver diseases.This article reviews the studies on the role and mechanism of Tim-3 in different liver diseases and cells in recent years,in order to provide richer perspectives and ideas for the clinical diagnosis and treatment of liver diseases.

Efferocytosis refers to the process by which apoptotic cells are engulfed and cleared by phagocytes， including professional phagocytes， such as macrophages and dendritic cells， and non-professional phagocytes， such as epithelial cells. Liver macrophages are the main cells with the function of efferocytosis in the liver. In recent years， an increasing number of studies have shown that various acute and chronic liver diseases are associated with the efferocytosis function of liver macrophages， including acute liver injury， alcoholic liver disease， nonalcoholic fatty liver disease， autoimmune liver disease， liver fibrosis， and liver cancer. This article elaborates on the expression of molecules associated with the efferocytosis function of macrophages， the process of efferocytosis， and the role of efferocytosis function in different liver diseases， so as to provide new ideas for the treatment of liver diseases.

Primary biliary cholangitis （PBC） is an autoimmune liver disease characterized by progressive and non-purulent inflammation of small- and medium-sized bile ducts in the liver. Recent studies have shown that abnormal lipid metabolism is relatively common in patients with PBC， and 76% of PBC patients have dyslipidemia. The effects and harms of dyslipidemia have attracted much attention. Lipid metabolism disorders play an important role in the progression of PBC. This article mainly reviews the research advances in the manifestation， role， diagnosis， and treatment of lipid metabolism disorders in PBC， so as to provide new ideas for the treatment of PBC.