Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Background::Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-na?ve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48.Methods::A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results::A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10 5 copies/mL (compared with <10 5 copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P = 0.005). Conclusions::Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-na?ve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Neoadjuvant therapy for locally advanced colorectal cancer has made great progress in the past 20 years, but there are still limitations such as side effects, organ dysfunction and unsatisfactory control of metastasis. In recent years, with the improvement of surgical techniques and further development of molecular research, how to further improve local control, reduce distant metastasis, and even avoid surgery according to clinical remission to achieve organ preservation, is the current demand and research goal. With the advancement of molecular research, colorectal cancer has different treatment strategies based on microsatellite status. For patients with microsatellite instability locally advanced colorectal cancer, immune checkpoint inhibitor therapy significantly increased the pathologic complete response rate, reduced the incidence of adverse events and improved organ function compared with conventional chemoradiotherapy. For patients with microsatellite stable locally advanced colon cancer, neoadjuvant therapy is still in the exploratory stage. The standard of care is surgery combined with perioperative chemotherapy. For microsatellite stable locally advanced rectal cancer, the complete response rate is improved by enhancing neoadjuvant therapy, which helps to preserve organs. On the other hand, selective radiotherapy preserves organ function and improves quality of life. This article reviews the neoadjuvant treatment strategies for locally advanced colorectal cancer based on organ-sparing strategies.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2％(32/65),and the DCR was 89.2％(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6％(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95％CI:12.3～16.6 months)and 8.8 months(95％CI:6.9～10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5％)stopped using TACE because of stubborn vomiting,and 5 patients(7.6％)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3％)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5％)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5％)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3～4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

ObjectiveTo assess the microstructural involvement of gray matter in recovered COVID-19 patients using Synthetic MRI. MethodsThis study was conducted in 29 recovered COVID-19 patients， including severe group （SG， n=11） and ordinary group （OG， n=18）. Healthy volunteers matched by age， sex， BMI and years of education were selected as a healthy control group （HC=23 cases）. Each subject underwent synthetic MRI to generate quantitative T₁ and T₂ maps， and the T₁ and T₂ maps were segmented into 90 regions of interest （ROIs） using automatic anatomical labeling （AAL） mapping. T₁ and T₂ values for each ROI were obtained by averaging all voxels within the ROIs. The T₁ and T₂ values of the 90 brain regions between the three groups were compared. ResultsRelative to HC， the SG had significantly higher T2 values in bilateral orbital superior frontal gyrus， bilateral parahippocampal gyrus， bilateral putamen， bilateral middle temporal gyrus， bilateral Inferior temporal gyrus， left orbital superior frontal gyrus， left orbital inferior frontal gyrus， left gyrus rectus， left anterior cingulate and paracingulate gyri， right median cingulate and paracingulate gyri， left posterior cingulate gyrus， and left supramarginal gyrus （P＜0.05）； Relative to OG， SG showed significantly increased T₂ values in the left rectus gyrus， left parahippocampal gyrus， bilateral middle temporal gyrus， and bilateral inferior temporal gyrus （P＜0.05）. Relative to HC， the T₁ values of SG were significantly increased in bilateral orbital superior frontal gyrus， left rectus gyrus， left anterior cingulate and paracingulate gyri， right posterior cingulate gyrus， left parahippocampal gyrus， left lingual gyrus， left putamen， left thalamus（P＜0.05）； Relative to OG， the T₁ values of SG were significantly higher in the right posterior cingulate gyrus， right calcarine fissure and surrounding cortex， and left putamen （P＜0.05）. ConclusionsEven after recovering from COVID-19， patients may still have persistent or delayed damage to their brain gray matter structure， which is correlated with the severity of the condition. SyMRI can serve as a sensitive tool to assess the extent of microstructural damage to the central nervous system， aiding in early diagnosis of the disease.