AIM: To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS: Retrospective, noncomparative, interventional study. Ten surgical pearls were summarized and adapted from the ancient Chinese philosophy. Totally 346 cases(443 eyes)that underwent pars plana vitrectomy(PPV)at our hospial from January 2016 to February 2024 were selected. Flexible combinations of these pearls were applied according to the specific condition of each patient during surgeries. The efficacy and safety were analyzed, as well as the application frequencies according to the existence of tractional retinal detachment or not.RESULTS: A total of 473 times of surgeries were performed on all the patients. According to ancient Chinese allusions, ten surgical pearls were summarized from these surgeries. All PPVs went smoothly with the application of different combinations. Finally, almost all proliferative membranes were successfully peeled except for 10 patients(11 eyes), who went through strategy No.10(minimal membranectomy)that, only necessary relaxation incisions were made with most of the proliferative membranes left on purpose. The final visual acuities were mostly improved or stable(1.92±0.83 LogMAR preoperatively vs 1.16±0.85 LogMAR postoperatively, P<0.01). Postoperative complications mainly included early inflammatory responses in the anterior chamber and nuclear sclerosis. Recurrent vitreous hemorrhage, retinal detachment, and hyphema or neovascular glaucoma occurred in 1.9%(9/473), 3.2%(15/473), 0.4%(2/473)and 0.4%(2/473)times of PPVs, respectively. After 12/473(2.5%)times of PPVs, retinal detachment at the macular area still existed, and multiple times of subsequent PPVs were conducted. Final retinal attachment at the macular area was realized in 98.9% eyes. Those 5 unattached eyes were with heavily reproliferated membranes and subsequent tractional retinal detachment recurrence under the oil, and three of them were scleral buckled additionally.CONCLUSION:These 10 surgical strategies and technique pearls were mostly effective and safe in the management of severe PDR patients. They were relatively easy to be memorized and applicated once the meaning of each Chinese idiom was understood. One can use different combinations flexibly according to a patient's specific condition.

BACKGROUND:Bone tissue defects are one of the most common diseases in orthopedics,and the current treatments for this disease are inadequate.The development of tissue engineering brings new hope for bone defect repair:by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site,it can effectively improve the microenvironment of bone tissue and promote osseointegration,which is the most promising research idea for large-size bone defect repair. OBJECTIVE:To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances,vascularization and neurotization on three aspects of bone microenvironment changes,and to provide new ideas and strategies for the treatment of large-size bone defects. METHODS:The search terms"bone tissue engineering,angiogenesis,neurotization,cytokines,bone morphogenetic protein,vascular endothelial growth factor,neuropeptides,bone microenvironment"in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1,2001 to December 31,2022 on CNKI,WanFang,Web of Science,Science Direct,and PubMed.Finally,109 articles were included for review. RESULTS AND CONCLUSION:(1)The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation,and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions,the local blood circulation network and the surrounding nerve tissue.(2)Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines,and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases.(3)Neovascular regeneration is key to initiating bone repair,as neovascularisation not only provides essential nutrients,osteoblasts and growth factors for bone repair,but is also a gateway for repair cells to enter the injury zone.(4)In addition to regulating the type,dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction.The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects.(5)Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing,bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways.(6)In the establishment of neuralized tissue-engineered bone,the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional.Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier.Neuropeptides secreted by glial cells act on the bone microenvironment,affecting bone healing,bone regeneration and the balance between osteogenesis and osteolysis.(7)There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis,such as the rapid diffusion and degradation of cytokines in the body and their loss of activity,the temporal and spatial distribution of angiogenesis-related growth factors,and the establishment of neurogenesis through the body's feedback regulatory mechanism,which need to be improved by subsequent studies.

BACKGROUND:Due to the young age of children,the occipital condyle and foramen magnum are not fully developed,and they are prone to various diseases and injuries in the occipitocervical junction,which requires surgical treatment in severe cases.However,anatomical parameters for the development of the occipital condyle and foramen magnum in children are lacking. OBJECTIVE:To measure the morphological structure of the occipital condyle and foramen magnum by three-dimensional reconstruction technique,and to provide important anatomical parameters for occipitocervical junction lesions,related surgical procedures and forensic identification. METHODS:Imaging data of 389 cases of primitive children and adolescents involved in skull base undergoing spiral CT scanning(247 males and 142 females)aged 1-18 years were collected and divided into 1-3-year-old group,4-6-year-old group,7-9-year-old group,10-12-year-old group,13-15-year-old group,and 16-18-year-old group according to their age.Mimics 16.0 software was used to reconstruct the skull base and measure the length and width of the foramen magnum.A formula was used to calculate the area and index of the foramen magnum.We measured the length,width and height of the occipital condyle,the angle between the long axis and the sagittal axis of the occipital condyle(O-S angle),the included angle between the midpoint of the front and back edges of the foramen magnum and the connection between the back edge of occipital condyle and the intersection point of the foramen magnum(F-O angle),and the included angle between the midpoint of the front and back edges of the foramen magnum and the midpoint of the back wall of the sublingual neural tube(F-H angle).Gender,side and age differences were analyzed among the indicators. RESULTS AND CONCLUSION:(1)In foramen magnum measurement,there was no significant difference between sexes in the index of the foramen magnum(P>0.05),but there were significant differences in length,width and area of the foramen magnum(P<0.05).(2)The O-S angle,F-O angle and F-H angle of the occipitral condyle were not significantly different between genders(P>0.05),but length,width and height of the occipital condyle were significantly different between genders(P<0.05).(3)There were no significant differences in the length of the occipital condyle among different groups(P>0.05),but there were significant differences in the width and height of the occipital condyle,O-S angle,F-O angle and F-H angle among different groups(P<0.05).(4)Length,width and area of the foramen magnum,length,width and height of the occipital condyle showed a wavy increasing trend with the increase of age,while O-S,F-O and F-H angles showed a wavy decreasing trend with the increase of age,while the index of the foramen magnum showed no significant change.(5)In conclusion,there are gender and lateral differences in the morphological indexes of the foramen magnum and the occipital condyle in children.These differences can provide an important reference for clinical surgical approach selection and forensic examination.

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system in which neuropathological changes precede cognitive dysfunction and behavioral impairment. Currently, early diagnosis of AD is based on invasive and expensive testing techniques that are difficult to use widely in the clinical setting. Therefore, there is an urgent need for new markers to detect AD at an early stage. The eye, as an extension of the brain, has been found to show earlier onset of ocular pathologic changes in patients with AD compared to brain pathologic changes, such as retinal structural abnormalities, visual dysfunction, retinal abnormal protein accumulation, choroidal thickness changes, decreased corneal nerve fiber density, deposition of abnormal Aβ proteins in the lens, and pupillary light decreased sensitivity of response, etc. This article reviews the ocular pathologic changes in AD patients in recent years to provide new ideas for the early clinical diagnosis of AD.

BACKGROUND:A large number of studies have confirmed that tissue engineering scaffolds can almost completely repair osteochondral defects.However,when osteochondral defects are complicated with infection,even after thorough debridement in the early stage,the repair effect of simple osteochondral tissue engineering scaffolds is often unsatisfactory. OBJECTIVE:To prepare fibroin/chitosan/nano-hydroxyapatite scaffold loaded with vancomycin hydrochloride sustained release microspheres,and to investigate the repair effect on infected osteochondral defect in distal femur of rabbit. METHODS:(1)Vancomycin hydrochloride sustained release microspheres were prepared by emulsified solvent evaporation method.The sustained-release microspheres of different weights(7.5,10,and 12.5 mg)were mixed with fibroin protein-chitosan nanohydroxyapatite solution,and the scaffolds of fibroin protein/chitosan/nano-hydroxyapatite were prepared by chemical crosslinking method.The porosity,water absorption and expansion rate,hot water loss rate of the scaffolds,and drug sustained-release in vitro were characterized.(2)Forty-five New Zealand white rabbits were randomly divided into blank group,control group,and experimental group,with 15 rabbits in each group.The osteochondral defect and infection model of the distal femur of the right hind limb was established in both groups.The blank group was not treated,and the control group was implanted with fibroin protein-chitosan-nano-hydroxyapatite scaffold.Vancomycin hydrochloride sustained-release microspheres(10 mg)of fibroin/chitosan/nano-hydroxyapatite scaffold were implanted in the defect of the experimental group.The levels of C-reactive protein and leukocytes in blood samples were detected 1 week after operation.At 4,8 and 12 weeks after operation,the tissue of the operative area was taken for gross observation and pathological observation. RESULTS AND CONCLUSION:(1)With the increase of sustained-release microspheres content,the porosity of scaffolds decreased,and there was significant difference among groups(P＜0.05).There were no significant differences in the pore size,water absorption expansion rate and hot water loss rate among the three groups(P＞0.05).Vancomycin hydrochloride was released sustainably in vitro for more than 30 days in all three groups of scaffolds.(2)The levels of C-reactive protein and leukocytes in blood samples of the experimental group were lower than those of the blank group and control group(P＜0.05).The repair of gross cartilage in the experimental group was significantly better than that in the blank group and the control group.Hematoxylin-eosin,Masson,Alcian blue and type Ⅱ collagen immunohistochemical stainings showed that the osteochondral repair effect of the experimental group was significantly better than that of the blank group and the control group at each time point.(3)The results showed that fibroin/chitosan/nano-hydroxyapatite scaffolds loaded with vancomycin hydrochloride sustained-release microspheres could effectively promote the repair of open osteochondral defects.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

OBJECTIVE To observe the regulation of aerobic oxidation mediated by HIF-1α/PDHK1 pathway by PNS, and to explore its mechanism of promoting the differentiation of Naive CD4+T cells into Treg cells. METHODS Naive CD4+T cells were isolated from the spleen of C57BL/6 mice by magnetic beads and induced to differentiate into Treg cells for in vitro culture. Naive CD4+T cells were divided into PNS treatment group(5, 10, 20 μg·mL−1), PNS combined with HIF-1α inhibitor(PX-478) group, and the control group was set up. The proportion of Treg cells differentiation was detected by flow cytometry. The expression of HIF-1α and PDHK1 protein was detected by Western blotting. The expression of HIF-1α, PDHK1 and FOXP3 mRNA was detected by real-time fluorescence quantitative PCR. The level of IL-10 in cell culture supernatant was detected by enzyme-linked immunosorbent assay. RESULTS PNS could significantly increase the proportion of Treg cells and the secretion level of IL-10, and increase the expression of FOXP3 mRNA in cells. At the same time, the expression of HIF-1α and PDHK1 protein and mRNA was inhibited. When the cells were treated with 10 μmol·L−1 PX-478 and then treated with 10 μg·mL−1 PNS, the expression of PDHK1 and FOXP3 and the differentiation ratio of Treg cells were not significantly different from those treated with 10 μmol·L−1 PX-478 alone. CONCLUSION PNS can reduce the expression level of PDHK1 by HIF-1α to enhance the aerobic oxidation of Naive CD4+T cells and promote their differentiation into Treg cells.

【Objective】 To establish a risk model for predicting spontaneous rupture bleeding of renal angiomyolipoma (RAML) in order to better assess and deal with the risk. 【Methods】 The information of 436 RAML patients diagnosed during Jan.2018 and Dec.2022 was retrospectively analyzed.According to the inclusion and exclusion criteria, 216 patients were included and divided into the rupture bleeding group (n=35) and non-rupture bleeding group (n=181).The factors influencing spontaneous rupture bleeding were identified using univariate and multivariate analysis, and a nomogram was constructed accordingly with R language.The nomogram was evaluated using Calibration curve and area under the receiver operator characteristic curve (AUC). 【Results】 It was found that clinical manifestations, tumor diameter, tumor convexity, tumor blood supply, and tuberous sclerosis complex (TSC) were significantly correlated with rupture bleeding.The Calibration curve fitted well with the nomogram.The AUC was 0.956 (95%CI: 0.856-0.943), indicating that the nomogram had good statistical performance. 【Conclusion】 The model can effectively predict the risk of spontaneous rupture bleeding of renal angiomyolipoma.

Objective:The objective of this study is to sequence whole genome of the rabies virus in the saliva specimen of a suspected rabies case with onset of rabies from a wildlife (hog badger) bite wound in Sichuan province, where the genetic variation characteristics of the virus was analyzed at the molecular level, so as to understand the prevalence and mutation of wildlife rabies virus in Sichuan province.Methods:Total viral RNA was extracted from the saliva specimen of the suspected rabies case. Then, rabies virus sequences were amplified using PCR with specific primers; the gene fragments obtained were sequenced, and the sequences obtained were spliced using biological software to obtain the whole genome sequence of the rabies virus strain. The genetic variation characteristics of the whole genome were analyzed.Results:The whole genome nucleotide sequence of a strain of rabies virus of hog badger origin (hereinafter referred to as SCR23-052) was obtained by sequencing, and NCBI online BLAST and comparison with several reference sequences showed that the composition and structure of the whole genome sequence of SCR23-052 conformed to the characteristics of the Lyssavirus under the Rhabdoviridae; the highest similarity in nucleotide and amino acid sequences in various gene regions was observed between SCR23-052 and the strains of Ningxia (J) and Chongqing (CQ92, 02050CHI). The sequence variability of SCR23-052 genome was significantly lower at the amino acid level than that at the nucleotide level, which indicated that most of the nucleotide variants in the protein-coding genes belonged to synonymous mutations. Phylogenetic analysis showed that SCR23-052 belonged to genotype V, which did not show any obvious mutation in the major antigenic site of the glycoprotein, underwent amino acid glycosylation at positions 56 and 338 by the online site prediction, and showed the least amino acid difference compared with the signal peptide sequence of the vaccine strain CTN181. The virus in this study has an A→T mutation at position 332 in the nucleoprotein major antigenic site with all reference vaccine strains, and an L→V mutation at position 379 in the B-cell epitope with the CTN181 vaccine strain. SCR23-052 was consistent with both genotype V reference strains at the nucleoprotein study site.Conclusions:The whole genome sequence of a wildlife strain of genotype V rabies virus of hog badger origin was obtained, which was different from that of the genotype I strain of rabies virus of dog origin that previously reported to be prevalent in Sichuan. The genome sequence of SCR23-052 differed from that of the reference vaccine strains to a varying degree, but the main virulence characteristics remained unaltered.

The classification of traditional Chinese medicine （TCM） syndromes is one of the core technical elements in the industry standard of Specification of Diagnosis and Therapeutic Effect Evaluation of Diseases and Syndromes in TCM. In the past，when clinical standards for TCM were formulated，the determination of TCM syndrome classification relied heavily on textbooks and expert experience，lacking systematic research. This approach thus failed to reflect the advancement and scientificity of the standards，thereby affecting their implementation and application. This article reviewed the presentation forms and technical methods of TCM syndrome classification，including the two-tier syndrome classification model with primary and secondary symptoms，as well as the application of modern literature research，ancient literature research，Delphi method，in-depth expert interviews，consensus conferences，and real-world research. When syndrome classification standards are developed，it is necessary to build upon modern literature research，adopt a mixed approach combining qualitative research and quantitative analysis results，and reach expert consensus through consensus conferences. Through systematic research，the scientificity，applicability，and coordination of TCM syndrome classification standards can be enhanced，providing guidance for the standardization of TCM.