BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

BACKGROUND:3D-printed bone tissue engineering scaffolds have obvious advantages in the research and clinical treatment of bone defect repair.As one of the important raw materials for 3D printed bone scaffolds,poly-L-lactic acid has a great potential for application in performing bone defect repair,but clinical patients with different bone defect causative factors have different requirements for the comprehensive performance of poly-L-lactic acid bone scaffolds.OBJECTIVE:To summarize and review the development of 3D printing technology and poly-L-lactic acid scaffolds and the design strategies chosen for scaffolds for bone repair in the setting of bone diseases such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis.METHODS:Literature from CNKI,WanFang,PubMed,Science Direct,and Web of Science databases were searched and screened from 1994 to 2024.Search terms were"3D printing,polylactic acid,bone tissue engineering scaffold,osteomyelitis,bone tumor,osteonecrosis,osteoporosis,bone defect"in Chinese and English.The screened 62 articles were systematically summarized and analyzed.RESULTS AND CONCLUSION:(1)Poly-L-lactic acid is considered to be an ideal raw material for artificial bone scaffold design due to its non-toxicity,processability,biocompatibility,and ability to self-degrade in the human environment.The application of 3D printing technology has enabled poly-L-lactic acid bone scaffolds to meet the multilayered and porous structural design requirements of biomimetic artificial bone repair materials,and to optimize the mechanical properties for better bone repair.(2)According to different bone disease microenvironments,timely adjustment of the functional design of poly-L-lactic acid scaffolds is important for the comprehensive osteogenic efficacy of the scaffolds.The article discusses the application of poly-L-lactic acid scaffolds in bone disease environments such as osteomyelitis,bone tumor,osteonecrosis,and osteoporosis,and highlights the importance of rationally grasping the timing of bone disease treatment and bone tissue regeneration for bone defects caused by different bone diseases.(3)Although poly-L-lactic acid scaffolds show potential in bone repair,there are still some problems,such as the need to further optimize the structural design of the scaffolds to fit new bone regeneration,enhance the bioactivity of the scaffolds,and take into account other functions(e.g.,antimicrobial,anti-tumor,and anti-osteoporosis)in order to adapt to the needs of bone tissue repair in different pathological environments.

BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the pathological characteristics of post-cholecystectomy specimens from patients with benign gallbladder diseases.Methods:This retrospective case series study analyzed clinical and pathological data from 1 712 patients who underwent cholecystectomy for benign gallbladder diseases at the Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between September 2022 and August 2024. The cohort included 757 males and 955 females, with an age ( M(IQR)) of 57(23) years (range: 14 to 91 years). Clinical and pathological features were analyzed. The χ2 test was used to compare clinical characteristics between patients with neoplastic and non-neoplastic polyps. Factors statistically significant in the χ2 test were subsequently included in a binary logistic regression analysis. Results:Postoperative pathological examination revealed gallbladder cancer in 7 patients (0.41%). These 7 cases, including 2 with pT3 stage cancer, were not detected preoperatively by various imaging examinations (ultrasound+magnetic resonance cholangiopancreatography/MRI plain scan in 3 cases, ultrasound+enhanced MRI in 1 case, ultrasound+enhanced CT in 2 cases, enhanced CT+enhanced MRI in 1 case). Gallbladder adenoma was found in 23 cases (1.34%), neoplastic polyps (including cholesterol polyps with dysplasia) in 29 cases (1.69%), and non-neoplastic polyps in 154 cases (9.00%). Statistically significant differences were observed in age and polyp number between patients with neoplastic and non-neoplastic polyps ( χ2=10.436 and 8.030; both P<0.05). Binary logistic regression analysis identified age ≥60 years ( P=0.003) and solitary polyps ( P=0.009) as risk factors for neoplastic polyps. Mucosal dysplasia was present in 164 cases (9.58%), including 9 cases of severe dysplasia, 4 of which exhibited focal carcinomatous transformation. Gallbladder polyps combined with stones were found in 90 cases (5.26%), among which 10 were associated with adenoma and mucosal dysplasia, and 2 showed focal carcinomatous transformation. Conclusions:The incidence of incidental gallbladder carcinoma was 0.41%. Intraoperative bile spillage can severely compromise prognosis. Preoperative imaging demonstrates a low detection rate for neoplastic polyps. Particular vigilance for neoplastic polyps is warranted in patients aged ≥60 years or with solitary polyps. Cholecystectomy should be performed promptly for benign gallbladder diseases meeting surgical indications.

With the continuous development of new surgical technology, new equipment and new concepts, the research focused in the field of surgery is also in constant change. Among them, there are still confusion and controversies in the current clinical practice when facing the one-stop proposition of benefit population screening, advantageous surgical indication decision-making, surgical intervention timing selection, postoperative complication prediction and management. Therefore, our team tries to analyze whether the concept of"co-management of liver and pancreas"exists in clinical practice from the aspects of anatomy, physiology, histology and embryology of liver and pancreas, as well as the interaction between liver and pancreas, and explore the relationship between liver and pancreas in anatomy and tissue embryonic development, and the relationship between the concept of"co-management of liver and pancreas"and pancreatitis and pancreatic tumors as well as the concept of “co-management of liver and pancreas” applied in neoadjuvant chemoradiotherapy, and attempts to establish a new treatment pathway for pancreatic diseases based on this concept, in order to provide a new idea, new scheme and new possibility for the clinical research of pancreatic diseases and pancreatic surgery.

OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

Both cathartic colon （CC） and cathartic-dependent constipation （CDC） are caused by the abuse of stimulant laxatives， while their concepts are not completely the same.Starting from the disease name of CC， this article traced the origin and evolution of the concept of CC， summarizes and compared the similarities and differences between CC， CDC， and slow transit constipation （STC）， and called for strict differentiation among the three.Furthermore， this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine （TCM） syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established， and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally， the paper provides an overview of current research on CDC in both Western medicine and TCM contexts， identifies future research directions， and suggests research pathways for refining and advancing CDC studies.