Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and investigate the causal relationships between immune cells and HCC through Mendelian randomization. Methods Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC. Results A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33⁺ HLA DR⁺ CD14dim (OR=1.097, 95%CI: 1.002–1.201, P=0.045, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR⁺⁺ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, P_Bonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33⁺HLA DR⁺ CD14dim and CD8 on CD28⁺CD45RA⁺CD8⁺T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR⁺⁺monocyte absolute count.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Humans ; Adult ; Retrospective Studies ; Neoplasm Recurrence, Local ; Hematologic Neoplasms/therapy* ; Busulfan/therapeutic use* ; Graft vs Host Disease/prevention & control* ; Chronic Disease ; Unrelated Donors ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Transplantation Conditioning

Gut microbiota is a bridge between the metabolism and health state of the host,which plays a very important role in maintaining homeostasis. Natural polysaccharides,widely existed in nature,are a kind of biological macromolecules with prebiotics effects,which can improve a degree of physiological status by selectively changing the gut microbiota structure and function,enhancing the content of short chain fatty acids(SCFAs)and decreasing the level of inflammatory cytokines. In addition,the majority of polysaccharides can be degraded by gut microbiota to enhance their bioavailability and to promote the health state of the host. In this paper we discuss the interaction among polysaccharides and gut microbiotanatural,degradation mechanism and review gut microbiota as a target in the treatment of metabolic diseases,so as to provide future prospects of natural polysaccharides as " prebiotics " functional factors in the field of biological medicine and health products.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Aim To explore the mechanism of Hispolon in the treatment of colon cancer by network pharmacology and cell experimental validation. Methods The potential targets of Hispolon were obtained from the Swiss Target Prediction website, and intersected with colon cancer targets from GeneCards and OMIM databases. The protein-protein interaction network of targets was built by the STRING11. 0 database. Meanwhile , the core targets of PPI network was explored by Cytoscape 3. 7. 2 software. Furthermore, the GO and KEGG pathway enrichment were analyzed by Metas- cape database. Finally, Western blotting was used to verify the regulation of Hispolon on some key targets in colon cancer cell SW480. Results Sixty-nine com-mon targets of Hispolon and colon cancer were obtained, which were colon cancer therapeutic targets. The core targets included BCL-2L1, EP300, CDK1, AR, MTOR and EGFR. The enrichment analysis showed that Hispolon played a role in the treatment of colon cancer by regulating the pathways in cancer, PI3K-Akt signaling pathway, prostate cancer and Mi- croRNAs in cancer. And the key targets in the pathway involved core targets such as BCL-2 LI, EP300, CDK1, MTOR and EGFR. Cell experiments confirmed that Hispolon promoted SW480 cell apoptosis by down- regulating the expression of target proteins BCL-2L1 and mTOR. Conclusions The discussion of the molecular mechanism of Hispolon in the treatment of colon cancer suggests that Hispolon may play a role in the treatment of colon cancer through multiple targets and multiple pathways. The results provide a scientific basis for the elucidation of the mechanisms and clinical application of Hispolon against colon cancer.

Objective:To control the quality of the reference sample of Wenjingtang by establishing the specific chromatograms. Method:On the basis of analyzing 15 batches of Wenjingtang freeze-dried powder samples， a high performance liquid chromatography （HPLC） specific chromatogram analysis method of Wenjingtang was established. The system adaptability was investigated and the retention time， relative retention value and deviation caused by different chromatographic columns and instruments were calculated by using the same brand of chromatographic columns， four different brands of chromatographic columns and instruments from three different manufacturers. The precision， repeatability and stability of this method was further completed. The possible chemical components of the freeze-dried powders were speculated and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MSⁿ）. Chromatographic separation was performed on ACQUITY UPLC BEH C₁₈ column （2.1 mm×100 mm， 1.7 μm） with acetonitrile （A）-0.1% formic acid aqueous solution （B） as mobile phase for gradient elution （0-2.8 min， 10%A； 2.8-8.0 min， 10%-18%A； 8.0-12.2 min， 18%-25%A； 12.2-15.3 min， 25%-40%A； 15.3-17.4 min， 40%A； 17.4-20.5 min， 40%-90%A）， and column temperature was set at 30 ℃ with flow rate of 0.4 mL·min^-1. Mass spectrometry was performed on electrospray ionization， data were collected under positive and negative ion modes， and the detection range was m/z 50-1 600. Result:Ten characteristic peaks were selected as the distinguishing features in this specific chromatograms， and eight of them were identified by comparing with the reference standards， including paeoniflorin （peak 1）， liquiritin apioside （peak 2）， liquiritin （peak 3）， ferulic acid （peak 4）， iquiritigenin （peak 6）， cinnamaldehyde （peak 8）， paeonol （peak 9）and glycyrrhizic acid （peak 10）. By mass spectrometry analysis， 30 compounds were identified， and the source of medicinal materials were assigned. It mainly contained triterpenoid saponins and flavonoids from Glycyrrhizae Radix et Rhizoma， ginsenosides from Ginseng Radix et Rhizoma， monoterpenoid glycosides and tannins from Paeoniae Radix Alba， steroids in Achyranthis Bidentatae Radix， phenolic acids in Angelicae Sinensis Radix. Conclusion:The established characteristic chromatographic analysis method of Wenjingtang is simple， stable and repeatable. The chemical composition of the freeze-dried powder of Wenjingtang is basically defined by mass spectrometry identification and source attribution， which can provide reference for the development and quality control of Wenjingtang in the future.

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies

Objective: To study the effects of superficial temporal artery and vein as recipient vessels for the free anterolateral thigh flap on the appearance and functions after maxillectomy. Methods: Clinical data of 21 patients with malignant maxillary tumors in Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University from January 2014 to November 2019, who were treated by free anterolateral thigh flap with temporal superficial vessels as the recipient vessels were analyzed retrospectively. There were 18 males and 3 females, with the age ranging from 29 to 73 years old, including 19 cases of squamous carcinoma, 1 case of adenoid cystic carcinoma and 1 case of osteosarcoma. Of those 7 patients underwent primary surgery, 14 patients received resurgery, and 6 patients had a history of postoperative radiotherapy and chemotherapy. Among 14 patients with resurgery, 13 had recurrent ipsilateral second site tumor and 1 had recurrent tumor, and all of them received the maxillectomy and reconstructive surgery with the free anterolateral thigh flap. Patients were evaluated with water swallow test and speech intelligibility score in 1, 3 and 6 months after operation. The data were statistically analyzed with SPSS 22.0 statistical software. Water swallow test results before and after operation were compared using the Wilcoxon rank sum test. The mean speech intelligibility scores before and after operation were compared by the paired t test. Results: Patients were followed up for 10-60 months. All free flaps survived after operation. No diplopia occurred. Breathing, swallowing and speaking functions were normal. No movement disorders caused by the donor of thigh flap. Water swallow test showed no phenomenon of water flowing into the nasal cavity or oral and nasal leakage with level Ⅰ for 4 cases, level Ⅱ for 13 cases, level Ⅲ for 3 cases and level Ⅳ for 1 case. The mean speech intelligibility scores before surgery and 1, 3 and 6 months after surgery were 4.31±0.13, 1.46±0.21, 2.15±0.45 and 2.87±0.76 respectively. There was statistically significant difference in the mean speech intelligibility scores between 1 and 6 months after surgery (F=78.456, P<0.05). Conclusion: It is safe and reliable to use the superficial temporal vessels as recipient vessels for free anterolateral thigh flap in the reconstruction of defect after maxillectomy in malignant tumors, with good outcomes of functions and a satisfactory restoration of outward appearance.
Adult ; Aged ; Female ; Free Tissue Flaps ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin Transplantation ; Thigh/surgery*