Objective:To evaluate the risk factors for pulmonary embolism in patients with spinal injury.Methods:Literature on risk factors for pulmonary embolism after spinal injury was searched on CNKI, Wanfang database, VIP Chinese Science, PubMed, Embase, Cochrane Library, Up to Date databases from inception through November 2023. A Meta-analysis was performed with the software of RevMan 5.4 after two researchers screened the literature independently according to the inclusion and exclusion criteria, extracted the data and evaluated their quality. Correlations of gender, age, surgical duration, intervertebral disc fusion, body mass index, comorbidity, medicine prophylaxis, deep venous thrombosis (DVT) history, and length of hospital stay with the incidence of pulmonary embolism in patients with spinal injury were evaluated.Results:A total of 10 studies were enrolled, including 2 prospective cohort studies and 8 cross-sectional studies. The total sample size was 401 698 patients, with 525 in the pulmonary embolism group and 401 173 in the non-pulmonary embolism group. The Meta analysis showed that gender ( OR=1.59, 95% CI 1.20, 1.97), age ( OR=1.58, 95% CI 1.19, 2.10), surgical duration ( OR=2.56, 95% CI 1.84, 3.56), DVT history ( OR=15.84, 95% CI 1.88, 133.25) and length of hospital stay ( OR=1.08, 95% CI 1.07, 1.09) were statistically significantly correlated with the incidence of pulmonary embolism in patients with spinal injury ( P<0.01), while intervertebral fusion, body mass index, comorbidity, and medicine prophylaxis were not correlated with the incidence of pulmonary embolism ( P>0.05). Conclusion:Gender, age, surgical duration, DVT history and length of hospital stay are risk factors for pulmonary embolism in patients with spinal injury.

Middle-aged and elderly patients with femoral neck fracture often suffer from basic diseases. Conservative treatment will significantly increase the incidence of complications. At present, surgical treatment is mostly advocated. Internal fixation is one of the effective treatment methods for middle-aged and elderly patients with femoral neck fracture. It has the advantages of improving hip joint function, accelerating patient recovery, and improving patient quality of life. At present, there are many choices of internal fixation in the world, each has its own advantages and disadvantages, and there is no unified standard. Different surgical methods can be selected according to various factors such as fracture type, patient′s physical condition and surgical auxiliary technology. This article reviews the clinical progress of internal fixation for femoral neck fractures in middle-aged and elderly patients from four aspects: the characteristics of femoral neck fractures in middle-aged and elderly patients, common internal fixation methods, 3D printing guide plate auxiliary technology and artificial intelligence auxiliary technology.

Objective To explore the value of vesical imaging reporting and data system(VI-RADS)combined with absolute tumor-wall contact length(ABTCL)and actual tumor-wall contact length(ACTCL)in diagnosing muscle invasive bladder cancer(MIBC).Methods The MRI data of 113 patients with pathologically confirmed bladder cancer(BCa)were analyzed retrospectively.All patients underwent conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast enhanced(DCE)MRI before sur-gery.Two radiologists independently evaluated MRI images based on VI-RADS score,and measured quantitative parameters,inclu-ding ABTCL and ACTCL.The Chi-square test was used to compare the difference of VI-RADS scores between MIBC and non-mus-cle invasive bladder cancer(NMIBC).Quantitative parameters between MIBC and NMIBC were compared by Mann-Whitney U test.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of VI-RADS,quantitative parameters and VI-RADS combined with quantitative parameters in the diagnosis of MIBC.Results VI-RADS,ABTCL and ACTCL had significant differences between MIBC and NMIBC(P＜0.05).The area under the curve(AUC)for VI-RADS,ABTCL and ACTCL in diagno-sing MIBC were 0.89,0.76 and 0.77,respectively.There was no significant difference between the AUC for ABTCL and ACTCL(P＞0.05).The AUC for VI-RADS combined with ABTCL or ACTCL in diagnosing MIBC was 0.93,higher than that of only VI-RADS(P＜0.05).Conclusion The combination of VI-RADS with either ABTCL or ACTCL can effectively improve the diagnostic performance of MIBC.ABTCL obtainedby linear measurement is easier to implement in clinical practice than ACTCL obtained by curved measurement.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Background: Serum C-peptide results from various routine methods used in China are highly variable, warranting well-performing methods to serve as an accuracy base to improve the harmonization of C-peptide measurements in China. We developed an accurate isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC–MS/MS) method for serum C-peptide measurement and explored its use in harmonization. Methods: After protein precipitation with ZnSO4 solution, C-peptide was extracted from serum samples by anion-exchange solid-phase extraction and quantified by ID-LC–MS/MS in positive ion mode. The precision and analytical recovery of the ID-LC–MS/MS method were assessed. Seventy-six serum samples were analyzed using the ID-LC–MS/MS method and six routine immunoassays. Ordinary linear regression (OLR) and Bland-Altman (BA) analyses were conducted to evaluate the relationship between the ID-LC–MS/MS method and routine immunoassays. Five serum pool samples assigned using the ID-LC–MS/MS method were used to recalibrate the routine assays. OLR and BA analyses were re-conducted after recalibration. Results: The within-run, between-run, and total precision for the ID-LC–MS/MS method at four concentrations were 1.0%–2.1%, 0.6%–1.2%, and 1.3%–2.2%, respectively. The analytical recoveries for the ID-LC–MS/MS method at three concentrations were 100.3%–100.7%, 100.4%–101.0%, and 99.6%–100.7%. The developed method and the immunoassays were strongly correlated, with all R2 >0.98. The comparability among the immunoassays was substantially improved after recalibration. Conclusions The performance of the ID-LC–MS/MS method was carefully validated, and this method can be used to improve the harmonization of serum C-peptide measurements in China.

Objective:To investigate the effect of chemotherapy combined with sorafenib on the prognosis of FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia and to find a more effective treatment.Methods:The clinical data of 60 patients who were newly diagnosed with acute myeloid leukemia and who received treatment in The Second Affiliated Hospital of Qiqihar Medical University from January 2015 to January 2017 were retrospectively analyzed. The patients were divided into three groups according to whether they were positive for FLT3-ITD and the treatment method they used. The observation group (FLT3-ITD-positive, n = 19) were treated with sorafenib based on routine chemotherapy. The control group 1 (FLT3-ITD-positive, n = 21) was treated only with routine chemotherapy. The control group 2 (FLT3-ITD-negative, n = 20) was treated only with routine chemotherapy. After the first and fourth courses of treatment, clinical efficacy was compared among the three groups. Results:After the first course of treatment, the complete remission rate in control group 2 was 50.0% (10/20), which was significantly higher than 15.8% (3/19) in the observation group and 4.8% (1/21) in the control group 1 ( H = 13.39, P < 0.05). After the fourth course of treatment, the complete remission rate in the observation group, control group 2, and control group 1 was 63.2% (12/19), 60.0% (12/20), and 4.8% (1/21), respectively, and the differences were statistically significant ( H = 19.21, P < 0.05). Four-year follow-up results showed that the median survival time in the observation group, control group 1, and control group 2 was 36.63, 24.15, and 45.00 months respectively. The event-free survival in the observation group, control group 1, and control group 2 was 18.00, 9.82, and 24.90 months, respectively. The median survival time and the event-free survival in the control group 2 were significantly longer than those in the observation group and control group 1 ( χ2 = 19.93, 23.04, both P < 0.001). Conclusion:Chemotherapy combined with sorafenib for treating newly-diagnosed FLT3-ITD-positive acute myeloid leukemia can provide comprehensive benefits and have advantages for survival over chemotherapy without sorafenib and chemotherapy alone.

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.
Glycosyltransferases/genetics* ; Plants ; Saponins/chemistry* ; Triterpenes

Both natural ginsenoside F2 and unnatural ginsenoside 3β,20S-Di-O-Glc-DM were reported to exhibit anti-tumor activity. Traditional approaches for producing them rely on direct extraction from Panax ginseng, enzymatic catalysis or chemical synthesis, all of which result in low yield and high cost. Metabolic engineering of microbes has been recognized as a green and sustainable biotechnology to produce natural and unnatural products. Hence we engineered the complete biosynthetic pathways of F2 and 3β,20S-Di-O-Glc-DM in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titers of F2 and 3β,20S-Di-O-Glc-DM were increased from 1.2 to 21.0 mg/L and from 82.0 to 346.1 mg/L at shake flask level, respectively, by multistep metabolic engineering strategies. Additionally, pharmacological evaluation showed that both F2 and 3β,20S-Di-O-Glc-DM exhibited anti-pancreatic cancer activity and the activity of 3β,20S-Di-O-Glc-DM was even better. Furthermore, the titer of 3β,20S-Di-O-Glc-DM reached 2.6 g/L by fed-batch fermentation in a 3 L bioreactor. To our knowledge, this is the first report on demonstrating the anti-pancreatic cancer activity of F2 and 3β,20S-Di-O-Glc-DM, and achieving their de novo biosynthesis by the engineered yeasts. Our work presents an alternative approach to produce F2 and 3β,20S-Di-O-Glc-DM from renewable biomass, which lays a foundation for drug research and development.

Microglia (MG) are resident immune cells in the central nervous system (CNS) and the first defense line of CNS damage. The maintenance of MG function requires abundant energy, and lipid can serve as an energy source for the brain when glucose utilization is limited, and lipid can also function as signaling molecule. Alzheimer's disease (AD) is the most common neurodegenerative disease, and MG lipid metabolism plays an important role in the development of this disease. Drugs targeting lipid metabolism provide a new direction for AD treatment. This review starts with the specific mechanism of lipid metabolism in MG, and briefly introduces the effect of lipid metabolism on MG function and its role in AD.

Numerous studies have suggested that liquid-liquid phase separation (LLPS) may be involved in occurrence and progression of neurodegenerative diseases through mediating immune inflammation, transcriptional regulation, protein homeostasis, genomic stability, and oxidative stress, and regulation of LLPS-mediated protein homeostasis has attracted particular attention. Therefore, this paper reviews the research progress of mechanism of protein homeostasis regulation in neurodegenerative diseases in recent years, and discusses the prospect of LLPS related research.