OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.

Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

In the context of "New Era" and "New Medicine", the teaching team of laboratory diagnostics proposed a new teaching method of PDCA (Plan, Do, Check, Action) cycle to innovate the instructional design and implementation of laboratory diagnosis on the base of traditional teaching model. Through optimizing the curriculum system, integrating superior resources, taking full advantage of information technology, mobilizing the virtual simulation laboratory, implementing moral education and multiple comprehensive evaluation results, the self-learning enthusiasm, innovation and development ability of students were improved significantly, accompanied with high humanistic care spirit. Moreover, the enthusiasm of participating in scientific research activities and professional competitions was enhanced obviously. Therefore, we believe that the PDCA cycle, with notable successes, deserves high promotion value and wide application.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein(ABI3BP)on vesicular stomatitis virus(VSV)genome replication and innate immune signaling pathway. Methods The small interfering RNA(siRNA)was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells.VSV-green fluorescent protein(VSV-GFP)-infected cell model was established.The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining.The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection;western blotting was performed to detect the changes in interferon regulatory factor 3(IRF3)andTANK-binding kinase 1(TBK1)phosphorylation levels. Results The VSV-GFP-infected BJ-5ta cell model was successfully established.Efficient knockdown of ABI3BP in BJ-5ta cells was achieved.Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown.Compared with the control group,the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2-3.5 times(P＜0.01)and 2.2-4.0 times(P＜0.01)respectively when infected with VSV of multiplicity of infection 0.1 and 1.The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection.The activation of type-Ⅰ interferon pathway,as determined by phosphorylated IRF3 and phosphorylated TBK1,was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection. Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure.ABI3BP gene deletion promotes RNA virus replication,and ABI3BP is an important molecule that maintains the integrity of type Ⅰ interferon pathway.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.