Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.

Gallbladder carcinoma,a relatively rare malignancy within the biliary tract,presents a grave prognosis primarily due to asymptomatic early stages leading to advanced stage diagnosis and the absence of efficacious treatment options.Research has identified chronic inflammation,predom-inantly caused by gallstones,as a critical etiological factor.While surgical intervention offers potential curative outcomes in early stages,the majority of cases are identified too late for optimal surgical outcomes.Chemotherapy and targeted therapy,despite offering new therapeutic avenues,have not significantly improved overall survival rates.Thus,understanding the pathogenesis of gallbladder cancer,especially its association with key genetic and molecular pathways,is imperative for devising novel therapeutic strategies.This review delineates the epidemiology,pathogenesis,current treat-ment modalities,and research advancements in gallbladder cancer,aiming to provide innovative in-sights for clinical management and guide future research endeavors.

Objective To investigate the effect of amygdalin(AD)on fracture healing in osteoporotic(OP)rats and its possible mechanism.Methods SD rats were randomly divided into sham group,model group,inhibitor group and low,medium,high dose experimental groups,12 rats in each group.The OP rat model was established by bilateral ovariectomy.After the model was successfully established,rats in low,medium and high dose experimental groups were intraperitoneally injected with 0.1,0.5 and 1.0 mg·kg-1 AD;the inhibitor group was intraperitoneally injected with 5.0 mg·kg-1 H-89[cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate response element binding protein(cAMP/PKA/CREB)pathway inhibitor]+1.0 mg·kg-1 AD;sham group and model group were intraperitoneally injected with the same amount of 0.9％NaCl,once a day for 90 days.Micro-computer tomography was applied to observe the microstructure of the epiphysis in rats;the biomechanical status of femur was evaluated by orthopedic biomechanical test;the contents of serum osteocalcin(OC),C-terminal telopeptides of type Ⅰ collagen(CTX-Ⅰ),bone morphogenetic protein 2(BMP-2)and cAMP were detected by enzyme-linked immunosorbent assay(ELISA);the level of oxidative stress products in rat serum was detected by kit;Western blot was used to detect the expression of alkaline phosphatase(ALP)and cAMP/PKA/CREB signaling pathway protein(p-PKA/PKA,p-CREB/CREB)in rat bone tissue.Results The bone mineral density of sham group,model group and low,medium,high dose experimental groups,inhibitor group were(251.54±15.41),(135.82±10.92),(173.57±12.65),(204.31±14.48),(235.62±11.37)and(187.83±13.64)mg·cm-3;the contents of cAMP were(0.85±0.06),(0.20±0.03),(0.34±0.07),(0.48±0.09),(0.81±0.12)and(0.57±0.06)μmol·L-1;the expression of p-PKA/PKA were 0.96±0.08,0.06±0.02,0.35±0.04,0.67±0.07,0.94±0.09 and 0.37±0.05;p-CREB/CREB protein were 0.92±0.12,0.04±0.01,0.28±0.03,0.59±0.06,0.91±0.10 and 0.29±0.04,respectively.There were significant differences in the above indexes between sham group and model group,between low,medium,high dose experimental groups and model group,between inhibitor group and high dose experimental group(all P＜0.05).Conclusion AD can reduce oxidative stress,promote fracture healing and alleviate OP symptoms in rats.The mechanism may be related to the activation of cAMP/PKA/CREB signaling pathway.

Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95％CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.

Objective:To investigate the efficacy of posterior reduction and fixation combined with pedicle subtraction osteotomy (PSO) in the treatment of ankylosing spondylitis (AS) kyphotic deformity complicated by upper cervical spine injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 8 patients with AS kyphotic deformity complicated by upper cervical spine injury, who were admitted to First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2022. All were males, aged 32-58 years [(46.9±8.7)years]. Acute injury was found in 1 patient and chronic injuries in 7 patients, including 3 with cervicothoracic kyphotic deformity and 5 with thoracolumbar kyphotic deformity. Five patients were complicated by odontoid fractures, 1 by C 2-C 3 fracture and 2 by atlantoaxial dislocation. According to American Spinal Injury Association (ASIA) scale, 2 patients were with grade C, 3 with grade D, and 3 with grade E. The patients were treated with posterior upper cervical reduction and fixation combined with cervicothoracic PSO or thoracolumbar PSO respectively according to the location of the deformity. The operation time and intraoperative blood loss were recorded. Neck disability index (NDI), visual analogue scale (VAS), C 0-C 2 angle, C 1-C 2 angle, cervical lordosis angle (CL), head tilt angle (HT), chin-brow vertical angle (CBVA), cervical sagittal vertical axis (CSVA), and sagittal vertical axis (SVA) were compared before surgery, at 1 week and 3, 6, 12 months after surgery, and at the last follow-up. The healing of fractures and fusion of osteotomy site were recorded at 12 months after surgery. Recovery of neurological function was observed at the last follow-up. Incidence of complications was observed. Results:Patients were all followed up for 12-24 months [(17.0±5.4)months]. The operation time was 5.5-7.2 hours [(6.2±0.6)hours] and the intraoperative blood loss was 480-800 ml [(629.4±124.0)ml]. The NDI scores at 1 week and 3, 6, 12 months after surgery, and at the last follow-up were (14.6±2.6)points, (13.6±2.8)points, (12.8±2.4)points, (12.8±2.7)points, and (12.8±2.6)points respectively, significantly lower than (29.6±8.5)points preoperatively ( P<0.01). There were no significant differences in NDI scores at various time points after surgery ( P>0.05). The VAS scores were 2.0(1.0, 3.0)points, 1.5(1.0, 2.0)points, 0.5(0.0, 1.8)points, 0.5(0.0, 1.7)points, and 0.5(0.0, 1.8)points respectively, significantly lower than 3.5(3.0, 4.8)points preoperatively ( P<0.01). The VAS score at 3 months postoperatively was lower than that at 1 week postoperatively ( P<0.05), and the VAS score at 6 months postoperatively was lower than that at 3 months postoperatively ( P<0.05). There were no statistically significant differences in VAS scores at 6, 12 months postoperatively, and at the last follow-up ( P>0.05). There were no statistically significant differences between C 0-C 2 angle and C 1-C 2 angle preoperatively and at different time points postoperatively ( P>0.05). At 1 week and 3, 6, 12 months postoperatively and at the last follow-up, the CL values were -8.5(-5.3, -11.9)°, -8.6(-5.5, -11.9)°, -8.4(5.2, -12.1)°, -8.8(-5.6, -12.4)°, and -8.7(-5.3, -12.5)° respectively, significantly higher than 1.2(9.5, -4.8)° preoperatively ( P<0.01); the HT values were 6.1(4.5, 9.6)°, 6.1(4.3, 9.4)°, 6.0(4.2, 8.9)°, 6.0(4.2, 9.2)°, and 6.1(4.3, 9.2)° respectively, significantly lower than 17.0(10.3, 22.0)° preoperatively ( P<0.01); the CBVA values were (23.2±5.0)°, (23.1±4.8)°, (23.0±4.7)°, (23.1±4.7)°, and (23.1±4.9)° respectively, significantly lower than (44.1±9.8)° preoperatively ( P<0.01); the CSVA values were 5.2(4.2, 7.5)cm, 5.4(4.1, 7.1)cm, 4.7(4.0, 7.4)cm, 5.4(4.1, 7.0)cm, and 5.1(4.3, 6.5)cm respectively, significantly shorter than 9.0(7.8, 9.3)cm preoperatively ( P<0.01); the SVA values were 7.7(6.2, 13.7)cm, 7.5(6.0, 13.4)cm, 7.6(6.2, 13.2)cm, 7.4(6.3, 13.1)cm, and 7.5(6.2, 13.2)cm respectively, significantly shorter than 16.8(8.2, 27.2)cm preoperatively ( P<0.05). There were no statistically significant differences among CL, HT, CBVA, CSVA, and SVA values at different time points after surgery ( P>0.05). All the fractures healed at 12 months after surgery and Bridwell grade I healing was achieved at all the osteotomy sites. At the last follow-up, all the patients were classified as ASIA grade E, significantly improved compared with preoperatively ( P<0.01). One patient had transient C 8 nerve paralysis after surgery and recovered after 4 weeks′ treatment. The remaining patients did not develop any infection or internal fixation-related complications, such as broken rods, broken screws, or loose screws. Conclusion:For AS kyphosis deformity complicated with upper cervical injury, posterior reduction and fixation combined with cervicothoracic or thoracolumbar PSO can effectively promote functional recovery, relieve pain, maintain overall trunk balance, improve neurological symptoms, and reduce the incidence of complications.

Objective:To evaluate the safety and effectiveness of single posterior osteotomy in the correction of rigid cervical spine deformities (CSD) and to explore the indications and key surgical techniques involved.Methods:A retrospective analysis was conducted on the clinical data of 9 patients with rigid CSD who underwent single posterior osteotomy correction between June 2012 and June 2023 in the Department of Spine Surgery at the First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 4 males and 5 females, with a mean age of 19.8±27.2 years (range, 7-48 years). Among these, 5 cases were congenital CSD, 3 were post-tuberculosis deformities, and 1 was iatrogenic. Various coronal and sagittal alignment parameters were measured, including C 1, 2 angle, cervical lordosis (CL), structural scoliosis angle (SSA), structural kyphosis angle (SKA), head tilt (HT), C 2-C 7 sagittal vertical axis (CSVA), sagittal vertical axis (SVA), coronal balance distance (CBD), T 1 slope (T 1S), and the difference between T 1 tilt and cervical lordosis (T 1S-CL). Clinical outcomes were assessed using the neck disability index (NDI), visual analogue scale (VAS), and Scoliosis Research Society-22 questionnaire (SRS-22). Results:The average operation time was 273.9±76.1 min, with an average blood loss of 472.2±128.8 ml. All 9 patients were followed up for an average of 45.2±41.8 months (range, 12-116 months). A total of 7 patients underwent single-segment osteotomies (C 3, C 6 and C 7: 1 case each; C 5: 4 cases), and 2 patients underwent double-segment osteotomies (C 2 and C 7, C 3 and C 4). Four cases involved pedicle subtraction osteotomy (PSO), while 7 cases required vertebral column resection. The upper instrumented vertebra (UIV) was located at the occiput in 1 case and in the cervical spine in 8 cases. The lower instrumented vertebra (LIV) was located in the upper thoracic spine in 6 cases and in the cervical spine in 3 cases, with 2 of the latter cases having both UIV and LIV in the cervical spine. The average number of fused segments was 7.6±4.4 segments (range, 2-12 segments). All patients achieved successful bone fusion within an average of 8.8±3.2 months (range, 6-12 months). Preoperatively, the mean values for CL, SSA, SKA, HT, and CBD were 19.8° (17.2°, 30.5°), 27.4°(23.3°, 30.4°), 28.4°(25.6°, 30.1°), 9.0°(6.2°, 12.3°), and 18.5(12.3, 23.6) mm, respectively. Postoperative improvements were noted with values of -11.1°(-8.8°, -14.4°), 1.3°(0.8°, 1.6°), -11.1°(-8.6°, -14.5°), 1.6°(0.5°, 2.2°), and 9.4 (4.8-13.5) mm, respectively. At the final follow-up, these parameters were maintained, with values of -11.0°(-8.8°, -14.3°), 1.2°(0.8°, 1.5°), -11.0° (-8.6°, -14.3°), 1.5°(0.5°, 2.2°), and 9.4(4.8, 13.4) mm, respectively. Statistically significant improvements were observed between preoperative and postoperative measurements ( P<0.05), except for C 1, 2 angle, CSVA, SVA, T 1S, and T 1S-CL ( P>0.05). NDI and SRS-22 scores showed significant improvements postoperatively ( P<0.05), while VAS scores did not show a significant change ( P>0.05). Postoperative complications included transient nerve injury in two patients, one case of right central retinal artery occlusion, and one case of vertebral artery injury. Conclusion:This study confirms the safety and efficacy of single posterior osteotomy for treating rigid CSD of various etiologies. Standard PSO or modified techniques are effective for correcting cervical kyphosis, while hemivertebra resection and concave-side distraction are recommended for congenital scoliosis or kyphoscoliosis.

OBJECTIVE: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA. METHODS: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed. RESULTS: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3^rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ²=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034). CONCLUSIONS Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.
Humans ; Carbapenems/therapeutic use* ; Pseudomonas aeruginosa ; Soft Tissue Infections/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Hematologic Diseases ; Survival Analysis

ω-transaminase (ω-TA) is a natural biocatalyst that has good application potential in the synthesis of chiral amines. However, the poor stability and low activity of ω-TA in the process of catalyzing unnatural substrates greatly hampers its application. To overcome these shortcomings, the thermostability of (R)-ω-TA (AtTA) from Aspergillus terreus was engineered by combining molecular dynamics simulation assisted computer-aided design with random and combinatorial mutation. An optimal mutant AtTA-E104D/A246V/R266Q (M3) with synchronously enhanced thermostability and activity was obtained. Compared with the wild- type (WT) enzyme, the half-life t_1/2 (35 ℃) of M3 was prolonged by 4.8-time (from 17.8 min to 102.7 min), and the half deactivation temperature (T¹⁰₅₀) was increased from 38.1 ℃ to 40.3 ℃. The catalytic efficiencies toward pyruvate and 1-(R)-phenylethylamine of M3 were 1.59- and 1.56-fold that of WT. Molecular dynamics simulation and molecular docking showed that the reinforced stability of α-helix caused by the increase of hydrogen bond and hydrophobic interaction in molecules was the main reason for the improvement of enzyme thermostability. The enhanced hydrogen bond of substrate with surrounding amino acid residues and the enlarged substrate binding pocket contributed to the increased catalytic efficiency of M3. Substrate spectrum analysis revealed that the catalytic performance of M3 on 11 aromatic ketones were higher than that of WT, which further showed the application potential of M3 in the synthesis of chiral amines.
Transaminases/chemistry* ; Molecular Docking Simulation ; Amines/chemistry* ; Pyruvic Acid/metabolism* ; Enzyme Stability

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.