Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods* ; Male ; Animals ; Swine ; Acupuncture Points ; Humans ; Swine, Miniature ; Needles

Objective:To explore the optimal duration of preoperative imatinib therapy in patients with locally advanced gastrointestinal stromal tumors (GIST) in order to optimize surgical timing and long-term survival benefits.Methods:A total of 171 patients with locally advanced GIST who received preoperative imatinib therapy and subsequent surgical resection between November 2012 and October 2024 at Fujian Cancer Hospital and Union Hospital of Fujian Medical University were retrospectively analyzed. Patients were divided into three groups according to the duration of preoperative imatinib treatment: short-term (≤6 months, n=50), intermediate-term (7-12 months, n=87), and long-term (>12 months, n=34). Imaging response, pathological efficacy, recurrence-free survival (RFS), and overall survival (OS) were compared among the groups. Univariate and multivariate Cox regression analyses were used to identify the optimal treatment duration. Results:The median duration of preoperative imatinib therapy was 9 (6, 12) months. After treatment, the average maximum tumor diameter decreased from (10.37±5.74) cm to (6.99±4.34) cm, with an average shrinkage of 31.5%. The objective response rates in the short-, intermediate-, and long-term groups were 50.0% (25/50), 58.6% (51/87), and 52.9% (18/34), respectively; high-grade pathological response rates were 28.0% (14/50), 37.9% (33/87), and 29.4% (10/34), with no statistically significant differences among groups (all P>0.05). With a median follow-up of 46 months, 39 patients experienced recurrence and 20 died. The intermediate-term group had 3- and 5-year RFS rates of 87.1% and 79.6%, respectively, significantly better than those of the short-term group (75.5% and 55.5%, P=0.004). The long-term group had 3- and 5-year RFS rates of 85.3% and 75.5%, which were between the other two groups, but not significantly different (all P>0.05). For OS, the intermediate-term group had 3- and 5-year rates of 97.3% and 92.7%, superior to the short-term group (84.4% and 72.4%, P=0.007), while the long-term group (88.2% and 79.4%) showed no significant advantage (all P>0.05). Stratified analysis revealed that among non-gastric primary tumor patients with c-Kit exon 11 mutations, partial response on imaging, or postoperative imatinib ≤24 months, the intermediate-term group had significantly better RFS and OS than the short-term group (all P<0.05), but had no differences compared to the long-term group ( P>0.05). Multivariate Cox regression analysis indicated that preoperative imatinib duration was not an independent factor for RFS ( P>0.05), but treatment for 7-12 months was an independent protective factor for OS ( HR=0.275, 95% CI: 0.089-0.851, P=0.025), while prolonging therapy beyond 12 months conferred no additional OS benefit ( P>0.05). Conclusions:In patients with locally advanced GIST, preoperative imatinib therapy for 7-12 months yielded the most favorable prognosis, with significantly improved RFS and OS compared to ≤6 months of treatment. Extending preoperative therapy beyond 12 months did not provide additional survival benefit.

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Objective:To screen the HIV standard strains with typical biological characteristics of HIV strains circulating in China through the isolation, culture, genotype and phenotype identification of HIV from the whole blood samples of HIV-infected persons, confirm genetic characteristics, traceability, and in line with the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023).Methods:Whole blood samples were collected from 48 HIV infected patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the samples and co-cultured with PBMCs isolated from healthy persons′ whole blood samples to isolate and culture HIV from infected persons. We determined concentration of p24 antigen and the virus titer in the culture supernatant. The viral RNA was extracted from the successfully isolated strains, and the gag, pol genes and env C2V3 fragments of the viral genome were amplified and sequenced. The genotype, gene recombination and drug resistance sites were determined according to the viral gene sequences. Virus infection and replication were monitored by inoculating the virus culture supernatant into Ghost cells expressing CCR5 or CXCR4 to determine the viral tropism.The formation of syncytium was observed by inoculating the virus culture supernatant into MT-2 cells to determine whether was a syncytium-induced phenotype. Results:Fourteen strains with p24 antigen concentration > 1 ng/ml in culture supernatant were isolated and cultured from 48 fresh EDTA anticoagulated whole blood samples of HIV infected persons. Of the 14 strains, only one strain with a titer≥10 5 TCID 50/ml, 8 strains with titers ≥10 4 TCID 50/ml, and the other 5 strains with titers≥10 3 TCID 50/ml. Phylogenetic analysis showed that the genotypes of the strains were 9 strains of subtype B, 3 strains of CRF01_AE and 2 strains of CRF07_BC recombinant. Genotypic resistance analysis showed that 11 strains contained drug resistance sites. Ghost cells were used to verify the tropism of the strains, and it was found that 8 strains were CCR5 tropism, 6 strains were CXCR4 & CCR5 dual tropism. Only 2 of the 14 strains could induce MT-2 cytopathic effect, which was syncytium-inducing phenotype. Conclusions:Fourteen HIV strains with typical biological and genetic characteristics were isolated to screen the standard HIV strains. Among which, 1 strain was evaluated as a standard HIV strain that meets the Standard Strains of Pathogenic Microorganism-technical Specifications for Establishment of HIV Strains (T/CPMA 027—2023). This study can also provide technical guidance for the screening of the HIV standard strains. Next step is to complete the application and reserve database construction according to the sharing mechanism of the HIV standard strains, to provide resources for the researches of HIV vaccines and drugs.

The use of two inhibitors of Mek1/2 and Gsk3β (2i) promotes the generation of mouse diploid and haploid embryonic stem cells (ESCs) from the inner cell mass of biparental and uniparental blastocysts, respectively. However, a system enabling long-term maintenance of imprints in ESCs has proven challenging. Here, we report that the use of a two-step a2i (alternative two inhibitors of Src and Gsk3β, TSa2i) derivation/culture protocol results in the establishment of androgenetic haploid ESCs (AG-haESCs) with stable DNA methylation at paternal DMRs (differentially DNA methylated regions) up to passage 60 that can efficiently support generating mice upon oocyte injection. We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations. Furthermore, we demonstrate that TSa2i-treated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation. Strikingly, AG-haESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells, in part through the enhanced proliferation of H19-DMR hypermethylated cells. Together, we establish AG-haESCs that can long-term maintain paternal imprints.

Objective:To investigate the combined value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in predicting pathological microvascular invasion (pMVI) preoperatively, and to determine the relationship between prediction results and prognosis in hepatocellular carcinoma (HCC) patients.Methods:A total of 181 newly diagnosed HCC patients were enrolled in this study. Imaging characteristics and the apparent diffusion coefficient (ADC) value of DWI were analyzed. The differences of imaging characteristics and ADC values between different pMVI groups were analyzed.Multivariate logistic regression and receiver operating characteristic (ROC) curve were used to analyze the value for pMVI prediction by using significant parameters. The patients were grouped based on MRI predicted MVI (mrMVI), and the relationship between mrMVI and recurrence free survival time (RFS) was analyzed.Results:Fifty-one patients were pMVI positive and 130 patients were pMVI negative. The ADC value in pMVI positive group were (1.10±0.17)×10 -3 mm 2/s, significantly lower than (1.27±0.22)×10 -3 mm 2/s of pEMVI negative group ( P<0.001). The incidence rates of incomplete enhancing "capsule" , non-smooth tumor margin, arterial peritumoral enhancement, mosaic architecture and peritumoral hypointensity on hepatobiliary phase (HBP) in pMVI positive group were significantly higher than those of negative group (all P<0.05). Multivariate logistic regression analysis showed that tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value were independently associated with pMVI. ROC analysis showed that the area under curve, sensitivity and specificity of pMVI predicted by combined parameters were 0.830, 76.5% and 81.5%, respectively. The median RFS of mrMVI positive group was 23.6 months, significantly lower than 38.2 months of mrEMVI negative group ( P=0.004). Conclusion:Tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value are independent predictors of pMVI in HCC, and mrMVI is related with RFS.

Objective:To investigate the combined value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in predicting pathological microvascular invasion (pMVI) preoperatively, and to determine the relationship between prediction results and prognosis in hepatocellular carcinoma (HCC) patients.Methods:A total of 181 newly diagnosed HCC patients were enrolled in this study. Imaging characteristics and the apparent diffusion coefficient (ADC) value of DWI were analyzed. The differences of imaging characteristics and ADC values between different pMVI groups were analyzed.Multivariate logistic regression and receiver operating characteristic (ROC) curve were used to analyze the value for pMVI prediction by using significant parameters. The patients were grouped based on MRI predicted MVI (mrMVI), and the relationship between mrMVI and recurrence free survival time (RFS) was analyzed.Results:Fifty-one patients were pMVI positive and 130 patients were pMVI negative. The ADC value in pMVI positive group were (1.10±0.17)×10 -3 mm 2/s, significantly lower than (1.27±0.22)×10 -3 mm 2/s of pEMVI negative group ( P<0.001). The incidence rates of incomplete enhancing "capsule" , non-smooth tumor margin, arterial peritumoral enhancement, mosaic architecture and peritumoral hypointensity on hepatobiliary phase (HBP) in pMVI positive group were significantly higher than those of negative group (all P<0.05). Multivariate logistic regression analysis showed that tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value were independently associated with pMVI. ROC analysis showed that the area under curve, sensitivity and specificity of pMVI predicted by combined parameters were 0.830, 76.5% and 81.5%, respectively. The median RFS of mrMVI positive group was 23.6 months, significantly lower than 38.2 months of mrEMVI negative group ( P=0.004). Conclusion:Tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value are independent predictors of pMVI in HCC, and mrMVI is related with RFS.

Objective To investigate the clinical value of Rheum officinale Ball.as a main agent in a tra-ditional Chinese medicine recipe combined with continuous hemoperfusion in patients with acute paraquat poison-ing(APP). Methods A total of 124 patients with APP were divided into three groups:A group(40 cases),B group(42 cases)and C group(42 cases). Before,3 days and 7 days after treatment,PⅢNP,CⅣ,TGF-β1, MDA,SOD and SOFA scores were observed. The correlation between PⅢNP and the concentration of paraquat were analyzed,and the outcomes in 28 days were compared.Results In admission,there were no differences in PⅢNP,CⅣ,TGF-β1,MDA,SOD and SOFA scores among three groups(P>0.05).After treatment for 3 days, MDA and SOFA scores were elevated in three groups compared with these three scores in the three groups at admis-sion. Group A was increased significantly;the activity of SOD were decreased,especially in A group decreased most significantly(P<0.05);After 7 days'treatment,MDA and SOFA scores were lower than those of 3 days af-ter treatment in three groups,especially in C group decreased most significantly(P < 0.05),the activity of SOD were higher than 3 days after treatment,especially in C group increased most significantly(P<0.05);After 3,7 days treatment,PⅢNP,CⅣ,TGF-β1 were increased gradually,C group increased slowly(P<0.05).PⅢNP in patients with APP was positively correlated with the concentration of paraquat(P < 0.05). The mortality rate of three groups were 65.00%,45.24%and 23.81%,there were significant difference among three groups(P<0.05). Conclusions Rheum officinale Ball.as a main agent in a traditional Chinese medicine recipe combined with con-tinuous hemoperfusion in patients with APP could decrease PⅢNP,CⅣ,TGF-β1 and MDA. The can enhance the expression of SOD and reduce the mortality rate of patients.

Objective To investigate the prognostic value of the texture analysis contrast-enhanced MR imaging (DCE-MRI) in predicting microvascular invasion in hepatocellular carcinoma (HCC) before operation. Methods Sixty patients with HCC confirmed by pathology in the Chinese Academy Medical Sciences from January 2014 to December 2016,were enrolled in our study retrospectively.According to the post-operative pathology, the patients were divided into positive microvascular invation[MVI(+)]group including 30 patients, and negative MVI[MVI(-)] group including 30 patients. All patients underwent normal MR and DCE-MRI before surgery.Sixty seven texture features were extracted from the original data of arterial phase (AP) and portal venous phase (PVP) of DCE-MRI. All data were calculated by using Omni-Kinetics(OK)software of the United States.The difference between MVI(+)group and MVI(-)group was statistically significant using the independent sample t test. The identified methods of the DCE-MR texture features in predicting MVI adopted the principal component analysis (PCA) and the establishing prediction model including dimensionality reduction, modeling, prediction and verification. The model was established by logistic regression method. According to the histopathology, 80% data of AP and PVP were used as training group[48 cases,MVI(+)and MVI(-)group 24 cases respectively],20% as validation group [12 cases, MVI(+) and MVI(-) group 6 cases respectively]. The DCE-MRI images of AP and PVP were modeled and cross-referenced respectively, and the diagnostic efficiency of ROC evaluation model was adopted. Results There were 15 significant different texture features of the AP and three significant different texture features of the PVP between MVI(+) group and MVI(-) group respectively. The PCA method extracted the important DCE-MRI texture features and analyzed the 15 features of AP.The UPP and energy showed a good correlation(r>0.90),therefore the UPP were removed.Fourteen texture features were analyzed using the PCA method.There were four important texture features including the GLCM Correlation, Hara Variance, GLCM sum Variance and GLCM sum Entropy in the AP. Moreover, there were three important texture features including GLCM difference Entropy, Long Run Low Grey Level Emphasis and GLCM difference Variance in the PVP.Through the prediction model was established and crossly validated. There were three significant different texture features in the AP of DCE-MRI,including GLCM Correlation, GLCM Contrast and GLCM sum Entropy.And there were two significant different texture features in the PVP of DCE-MRI,including GLCM difference Variance and Long Run Low Grey Level Emphasis.In the training and validation group,the areas under the ROC of the AP model and PVP model were 0.774,0.681,0.889 and 0.611 respectively.The diagnosed accuracy rate of the AP model(83.30%,10/12)was higher than that of the PVP model(42.00%,5/12).Conclusion The DCE-MRI texture analysis technique could predict the MVI of HCC before operation,and the predictive accuracy of the AP texture feature was higher.