Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective: Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. Methods: Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. Results: We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78–0.85). Conclusion A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Objective:To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome (XFS).Methods:A total of 20 patients were enrolled in the Department of Ophthalmology, People's Hospital of Hotan District from June 2020 to January 2021, including 10 patients with age-related cataract and 10 XFS patients combined with cataract, which were classified as cataract group and XFS group, respectively.A total of 50 to 100 μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group, and the differentially expressed proteins (DEPs) in XFS group were screened according to P<0.05 and fold change >1.5.Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-21).Written informed consent was obtained from each subject. Results:In comparison with the cataract group, 25 DEPs were identified in the XFS group, primarily involved in cell adhesion, receptor, hydrolase, and molecular transport.Specifically, there were 14 down-regulated proteins including complement factor H-related protein 1 (CFHR1), endoplasmic reticulum chaperone BiP (HSPA5), biglycan (BGN), FRAS1-related extracellular matrix protein 2 (FREM2), hemoglobin subunit delta (HBD), hemoglobin subunit gamma-1 (HBG1), lysosomal thioesterase PPT2 (PPT2) etc., and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2 (LTBP2), very low-density lipoprotein receptor (VLDLR), laminin subunit alpha-2 (LAMA2), coagulation factor Ⅸ (F9).Among them, FREM2 was the most significantly differentially expressed protein in XFS group with consistent expression levels across individual samples.GO analysis revealed that these DEPs mainly localized to the extracellular matrix of collagen, bound globin-hemoglobin complex, plasma lipoprotein particles and lysosomes.Molecular functions and biological processes showed that HBD and HBG1 were involved in cellular detoxification, PPT2 in hydrolase activity, and BGN and LTBP2 in glycosaminoglycan binding.KEGG signaling pathway analysis indicated that CFHR1 and F9 were associated with complement and coagulation cascade pathways, and FREM2 and LAMA2 were linked to the extracellular matrix interaction pathway.Conclusions:Disease progression of XFS may be associated with changes in extracellular matrix proteins, disruption of the blood-aqueous humor barrier, and potential inflammatory responses.The significant down-regulation of FREM2 protein may be a potential biomarker for XFS.

Objective: Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. Methods: Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. Results: We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78–0.85). Conclusion A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation.

Objective: Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. Methods: Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. Results: We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78–0.85). Conclusion A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.