Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

BACKGROUND:As a degradable scaffold material for bone tissue engineering,lactic acid is widely used in tissue regeneration and repair research,and plays an important role in promoting tissue healing,new bone formation and angiogenesis. OBJECTIVE:To observe the effect of lactic acid degradation products on osteoclasts and to investigate the effects of lactic-interfered osteoclast conditioned medium on the proliferation,migration and tube-forming capacity of human umbilical vein endothelial cells. METHODS:(1)The mouse monocyte macrophage cell line RAW264.7 at logarithmic growth period was selected,and adherent cells were cultured in the osteoclast induction medium(DMEM medium with nuclear factor-κB receptor-activating factor ligand and 10%fetal bovine serum)containing different concentrations of lactic acid(0,5,10,20 mmol/L).After 5 days of culture,tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining were conducted.After 24 hours of culture,RT-PCR was used to detect the mRNA expression of tartrate-resistant acid phosphatase 5.(2)RAW264.7 cells at logarithmic growth period were selected and adherent cells were divided into two groups.Control group was cultured in the osteoclast induction medium,while experimental group was cultured in the osteoclast induction medium containing 10 mmol/L lactic acid.After 5 days of culture,the medium in each group was removed and the cells in the two groups were cultured in the serum-free DMEM medium for another 24 hours.Cell supernatant was then collected and used as the conditioned medium after mixed with an equal volume of DMEM medium containing 10%fetal bovine serum.Human umbilical vein endothelial cells at the logarithmic growth phase were taken and separately co-cultured with the conditioned medium of the control and experimental groups.The proliferation,migration and tube-forming ability of human umbilical vein endothelial cells were observed by cell counting kit-8 assay,migration assay,scratch assay and tube-forming assay.The mRNA and protein expression of angiogenesis-related genes and proteins were observed by RT-PCR and western blot. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining showed that 5 and 10 mmol/L lactic acid promoted osteoclastic differentiation of RAW264.7 cells and the promoting effect of 10 mmol/L lactate was more significant.RT-PCR results showed that the expression of tartrate-resistant acid phosphatase-5 mRNA of osteoclast-related genes was the highest when the lactic acid concentration was 5,10,and 20 mmol/L(P<0.05),especially 10 mmol/L.Compared with the control group,the proliferation,migration and tube-forming abilities of human umbilical vein endothelial cells were significantly increased in the experimental group(P<0.05).Compared with the control group,the expression levels of vascular endothelial growth factor and angiogenin 1 mRNA and protein were increased in the experimental group(P<0.05).To conclude,lactate-induced osteoclast conditioned medium could promote the angiogenesis of endothelial cells,and the mechanism may be related to the promotion of the expression of vascular endothelial growth factor and angiogenin 1.

For women with type 1 diabetes mellitus (T1DM) reaching reproductive age, the disease course generally protracted, often accompanied by varying degrees of microvascular complications. Hence, the need for preconception planning and comprehensive screening and management of complications is urgent to avoid serious maternal and fetal complications. The recommended preconception glycated hemoglobin control target is currently set at<6.5%. In cases of unintended pregnancies where pre-existing microvascular complications are present, multidisciplinary standardized management during the pregnancy is essential. Although a multidisciplinary expert consensus on gestational management of T1DM has been published in China in 2020, several issues remain regarding the clinical management of T1DM in pregnancy across the nation. Strengthening nutritionally balanced management, actively and reasonably utilizing insulin therapy, and leveraging new technologies such as the internet plus artificial intelligence hold promise to achieve more optimal glucose control, reduce the incidence of maternal and fetal complications associated with T1DM, and ultimately achieve favorable outcomes for both mother and child.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

Feline herpesvirus type Ⅰ(FHV-1)was used as the vector.The gI and gE genes of FHV-1 were replaced with the feline calicivirus(FCV)VP1 gene and the red fluorescent protein(mCherry)gene by CRISPR/Cas9 systems and homologous recombination technology,and the re-combinant virus strain FHV △gI&gE/VP1-mCherry+was successfully rescued.The recombinant virus strain was purified by plaque assay.The biological characteristics and genetic stability of the recombinant virus were analyzed by indirect immunofluorescence assay,plaque morphological anal-ysis,and PCR.The results of the indirect immunofluorescence identification showed that the re-combinant virus FHV △gI&gE/VP1-mCherry+could express the VP1 protein in F81 cells,and the growth characteristics of the recombinant virus were not significantly different from those of the parent virus FHV-1.The plaque morphology and staining results indicated that the area of the plaque formed by the recombinant virus was smaller than that of the parent virus,suggesting that the spread ability of the recombinant virus between cells was reduced after the deletion of the gI and gE genes.The result of PCR showed that the VP1 gene could still be detected after 15 succes-sive passages of the recombinant virus,indicating that the recombinant virus had good genetic stability.In this study,the recombinant virus strain expressing the FCV VP1 protein was successfully prepared,which will lay a foundation for the development of engineered FCV and FHV-1 vaccine.

Feline herpesvirus type Ⅰ(FHV-1)was used as the vector.The gI and gE genes of FHV-1 were replaced with the feline calicivirus(FCV)VP1 gene and the red fluorescent protein(mCherry)gene by CRISPR/Cas9 systems and homologous recombination technology,and the re-combinant virus strain FHV △gI&gE/VP1-mCherry+was successfully rescued.The recombinant virus strain was purified by plaque assay.The biological characteristics and genetic stability of the recombinant virus were analyzed by indirect immunofluorescence assay,plaque morphological anal-ysis,and PCR.The results of the indirect immunofluorescence identification showed that the re-combinant virus FHV △gI&gE/VP1-mCherry+could express the VP1 protein in F81 cells,and the growth characteristics of the recombinant virus were not significantly different from those of the parent virus FHV-1.The plaque morphology and staining results indicated that the area of the plaque formed by the recombinant virus was smaller than that of the parent virus,suggesting that the spread ability of the recombinant virus between cells was reduced after the deletion of the gI and gE genes.The result of PCR showed that the VP1 gene could still be detected after 15 succes-sive passages of the recombinant virus,indicating that the recombinant virus had good genetic stability.In this study,the recombinant virus strain expressing the FCV VP1 protein was successfully prepared,which will lay a foundation for the development of engineered FCV and FHV-1 vaccine.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

For women with type 1 diabetes mellitus (T1DM) reaching reproductive age, the disease course generally protracted, often accompanied by varying degrees of microvascular complications. Hence, the need for preconception planning and comprehensive screening and management of complications is urgent to avoid serious maternal and fetal complications. The recommended preconception glycated hemoglobin control target is currently set at<6.5%. In cases of unintended pregnancies where pre-existing microvascular complications are present, multidisciplinary standardized management during the pregnancy is essential. Although a multidisciplinary expert consensus on gestational management of T1DM has been published in China in 2020, several issues remain regarding the clinical management of T1DM in pregnancy across the nation. Strengthening nutritionally balanced management, actively and reasonably utilizing insulin therapy, and leveraging new technologies such as the internet plus artificial intelligence hold promise to achieve more optimal glucose control, reduce the incidence of maternal and fetal complications associated with T1DM, and ultimately achieve favorable outcomes for both mother and child.

Objective To investigate the acupoint selection patterns for treating diabetic cardiac autonomic neuropathy(DCAN)using data mining techniques,providing evidence for clinical practice.Methods Literature on acupuncture treatment for DCAN was retrieved from CNKI,Wanfang,VIP,and PubMed.The publication dates of the included literature ranged from the inception of each database to April 2024.Descriptive analysis,association rule analysis,and cluster analysis were performed on acupoint prescriptions,with the selection patterns of meridians and acupoints were summarized.Results A total of 27 articles were included,involving 18 acupoints.The top 10 high-frequency acupoints were Neiguan(PC6),Xinshu(BL15),Pishu(BL20),Zusanli(ST36),Sanyinjiao(SP6),Shenmen(HT7),Taixi(KI3),Lingtai(GV10),Shendao(GV11),and Shenshu(BL23).The primary meridians selected were the bladder meridian of foot-taiyang and the pericardium meridian of hand-jueyin.Specific acupoint categories predominantly included back-shu points and five transport points.Association rule and cluster analyses identified core acupoint combinations centered on Xinshu,Neiguan,Pishu,and Zusanli.Conclusion The core acupoint combination for treating DCAN with acupuncture comprises Xinshu,Neiguan,Pishu,and Zusanli.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.