Objective:To evaluate the relevant factors to optimize the learning curve and the impact of the basic skills of endoscopic technology on the learning curve of gasless transaxillary posterior endoscopic thyroidectomy.Methods:A retrospective analysis was performed to evaluate the clinical outcomes of 50 patients who underwent Glandular Ultrasound-Assisted (GUA) thyroid surgery by a surgeon with a background in endoscopic thyroid surgery via the thoracic-areolar approach, and 50 patients operated on by a surgeon without such experience at the Thyroid Surgery Department of Jilin University China-Japan Union Hospital from Apr. to Dec. 2023. The patients were divided into two groups: the Endoscopic Experience Group and the Non-Endoscopic Experience Group. The Cumulative Sum Control Chart (CUSUM) was applied to construct learning curves for both groups, dividing the technical exploration period from the mastery period. The analysis compared the surgical time, postoperative first-day drainage volume, number of central lymph nodes dissected rates, and postoperative complications between the two groups and across the two phases.Results:The analysis of the learning curve revealed that the inflection point of the Endoscopic Experience Group was 15, while of the Non-Endoscopic Experience Group was 18. The learning curve was divided into the technical exploration stage and the proficient mastery stage. The operative time of technical exploration stagde was significantly longer than of proficient mastery stage of both group (183.46±36.13min vs.144.40±26.14min, P<0.001; 186.89±48.91min vs.131.59±22.90min; P<0.001) . The operative time in the proficient mastery stage of the Endoscopic Experience Group was longer than that of the Non-Endoscopic Experience Group (144.40±26.15min vs. 131.59±22.90min, P<0.05) . The postoperative drainage volume in the Endoscopic Experience Group was lower than that in Non-Endoscopic Experience Group in both stages (65.40±32.48mL vs.93.22±30.67mL, 57.40±15.35mL vs.78.50±28.30mL, P<0.05) , and the postoperative drainage volume in the proficient mastery stage of the Non-Endoscopic Experience Group was significantly lower than in the technical exploration stage (93.22±30.67mL vs.78.50±28.30mL, P<0.05) .No significant differences in central lymph node dissection numbers or postoperative complications were observed between the groups at both stages. Conclusions:There is a specific learning curve in the early stage of gasless transaxillary posterior endoscopic thyroidectomy. After crossing the learning curve, the operation time is obviously shortened with the improvement of the operator's surgical technique.Having a basic understanding of endoscopic technology in the early stage can reduce the occurrence of postoperative drainage, but has a minimal impact on the learning curve.

Aim To investigate the preventive and therapeutic effect of crocetin(Cro)on acute intestinal injury induced by radiation(RT)and its related mech-anism.Methods Forty mice were randomly divided into four groups:control group,radiation group(RT group),low-dose Cro intervention group(RT+Low-dose Cro group)and high-dose Cro intervention group(RT+High-dose Cro group).The RT group was given a single dose of 12Gy radiation to the abdomen.The Cro intervention group was treated with 25 mg·kg-1 and 100 mg·kg-1 Cro by gavage once a day before ra-diation until seven days after radiation.The mice in each group were weighed.The morphology of intestinal tissue was observed by HE staining.The levels of in-testinal inflammatory factors and oxidative stress were detected.The expressions of Lgr5,Ki67,lysozyme,ZO-1 and Occludin in small intestine tissuewere detected by immunohistochemistry.The expressions of Nrf2/HO-1 and NF-κB signaling related proteinswere detected by Western blot.Results Compared to the control group,mice in the RT group exhibited a significant decrease in body weight(P＜0.01).Additionally,they dis-played evident morphological damage to the small in-testine and elevated levels of pro-inflammatory factors(TNF-α,IL-6)as well as oxidative stress markers(in-creased ROS and MDA levels,decreased GSH and SOD activities)(P＜0.01).Moreover,there was an in-crease in Lgr5 and Ki67 positive cells within the crypts(P＜0.01).The expressions of Occludin,lysozyme,ZO-1,and HO-1 were reduced in small intestine while Nrf2,p-p65,and p-IκB expressions increased(P＜0.01).The improvements in the Cro group were sig-nificantly greater than the RT group(P＜0.01),with a more pronounced effect observed in the high-dose group.Conclusions Cro has a preventive and thera-peutic effect on radiation-induced intestinal injury,and its mechanism is related to anti-inflammation,anti-oxi-dation,improvement of intestinal barrier function,pro-motion of intestinal stem cell regeneration,enhance-ment of Nrf2/HO-1 signaling and reduction of NF-κB signaling activity.

Objective:To evaluate the efficacy and safety of radiotherapy combined with sintilimab and bevacizumab (anti-angiogenic agent) in patients with unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 80 patients with unresectable advanced HCC admitted to Shanghai Mengchao Cancer Hospital from January 2021 to September 2023 were retrospectively analyzed. All patients were divided into two groups based on treatment regimens: the systemic therapy group ( n=41) receiving sintilimab combined with bevacizumab, and combined radiotherapy group ( n=39) receiving radiotherapy plus sintilimab and bevacizumab. Efficacy was evaluated using the response evaluation criteria in solid tumors (RECIST) 1.1 version and modified RECIST for HCC. Treatment-related adverse events (TRAE) were assessed by the common terminology criteria for adverse events (CTCAE) 4.03 version. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and TRAE. Independent sample t-test was used for normally distributed quantitative data, and Chi-square test for qualitative data. Survival analysis was performed via Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression models were applied to analyze prognostic factors. Results:In terms of efficacy, no patient obtained complete response (CR) in the systemic therapy group, while 2 cases achieved CR in the combined radiotherapy group. The ORR was 22% (9/41) in the systemic therapy group and 59% (23/39) in the combined radiotherapy group ( P=0.001). The DCR was 85% (35/41) and 97% (38/39) in the two groups ( P=0.130), with the incidence of progressive disease of 15% (6/41) and 3% (1/39) ( P=0.130), respectively. The median PFS was 8.0 months (95% CI=6.8-9.2 months) in the combined radiotherapy group and 4.4 months (95% CI=4.1-4.7 months) in the systemic therapy group ( P=0.002). The median OS was 19.0 months (95% CI=15.5-22.5 months) in the combined radiotherapy group and 12.5 months (95% CI=9.4-15.6 months) in the systemic therapy group ( P=0.006). Radiotherapy was an independent protective factor for both PFS ( HR=0.474, 95% CI=0.289-0.778, P=0.003) and OS ( HR=0.403, 95% CI=0.218-0.744, P=0.004). The number of tumors >3 was an independent risk factor for both PFS ( HR=2.658, 95% CI=1.485-4.755, P=0.001) and OS ( HR=3.245, 95% CI=1.773-5.939, P=0.001). There was no significant difference in TRAE between two groups ( P > 0.05). Conclusions:Radiotherapy combined with sintilimab and bevacizumab shows high efficacy and acceptable safety in patients with unresectable advanced HCC.

Objective:To evaluate the relevant factors to optimize the learning curve and the impact of the basic skills of endoscopic technology on the learning curve of gasless transaxillary posterior endoscopic thyroidectomy.Methods:A retrospective analysis was performed to evaluate the clinical outcomes of 50 patients who underwent Glandular Ultrasound-Assisted (GUA) thyroid surgery by a surgeon with a background in endoscopic thyroid surgery via the thoracic-areolar approach, and 50 patients operated on by a surgeon without such experience at the Thyroid Surgery Department of Jilin University China-Japan Union Hospital from Apr. to Dec. 2023. The patients were divided into two groups: the Endoscopic Experience Group and the Non-Endoscopic Experience Group. The Cumulative Sum Control Chart (CUSUM) was applied to construct learning curves for both groups, dividing the technical exploration period from the mastery period. The analysis compared the surgical time, postoperative first-day drainage volume, number of central lymph nodes dissected rates, and postoperative complications between the two groups and across the two phases.Results:The analysis of the learning curve revealed that the inflection point of the Endoscopic Experience Group was 15, while of the Non-Endoscopic Experience Group was 18. The learning curve was divided into the technical exploration stage and the proficient mastery stage. The operative time of technical exploration stagde was significantly longer than of proficient mastery stage of both group (183.46±36.13min vs.144.40±26.14min, P<0.001; 186.89±48.91min vs.131.59±22.90min; P<0.001) . The operative time in the proficient mastery stage of the Endoscopic Experience Group was longer than that of the Non-Endoscopic Experience Group (144.40±26.15min vs. 131.59±22.90min, P<0.05) . The postoperative drainage volume in the Endoscopic Experience Group was lower than that in Non-Endoscopic Experience Group in both stages (65.40±32.48mL vs.93.22±30.67mL, 57.40±15.35mL vs.78.50±28.30mL, P<0.05) , and the postoperative drainage volume in the proficient mastery stage of the Non-Endoscopic Experience Group was significantly lower than in the technical exploration stage (93.22±30.67mL vs.78.50±28.30mL, P<0.05) .No significant differences in central lymph node dissection numbers or postoperative complications were observed between the groups at both stages. Conclusions:There is a specific learning curve in the early stage of gasless transaxillary posterior endoscopic thyroidectomy. After crossing the learning curve, the operation time is obviously shortened with the improvement of the operator's surgical technique.Having a basic understanding of endoscopic technology in the early stage can reduce the occurrence of postoperative drainage, but has a minimal impact on the learning curve.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

Aim To investigate the preventive and therapeutic effect of crocetin(Cro)on acute intestinal injury induced by radiation(RT)and its related mech-anism.Methods Forty mice were randomly divided into four groups:control group,radiation group(RT group),low-dose Cro intervention group(RT+Low-dose Cro group)and high-dose Cro intervention group(RT+High-dose Cro group).The RT group was given a single dose of 12Gy radiation to the abdomen.The Cro intervention group was treated with 25 mg·kg-1 and 100 mg·kg-1 Cro by gavage once a day before ra-diation until seven days after radiation.The mice in each group were weighed.The morphology of intestinal tissue was observed by HE staining.The levels of in-testinal inflammatory factors and oxidative stress were detected.The expressions of Lgr5,Ki67,lysozyme,ZO-1 and Occludin in small intestine tissuewere detected by immunohistochemistry.The expressions of Nrf2/HO-1 and NF-κB signaling related proteinswere detected by Western blot.Results Compared to the control group,mice in the RT group exhibited a significant decrease in body weight(P＜0.01).Additionally,they dis-played evident morphological damage to the small in-testine and elevated levels of pro-inflammatory factors(TNF-α,IL-6)as well as oxidative stress markers(in-creased ROS and MDA levels,decreased GSH and SOD activities)(P＜0.01).Moreover,there was an in-crease in Lgr5 and Ki67 positive cells within the crypts(P＜0.01).The expressions of Occludin,lysozyme,ZO-1,and HO-1 were reduced in small intestine while Nrf2,p-p65,and p-IκB expressions increased(P＜0.01).The improvements in the Cro group were sig-nificantly greater than the RT group(P＜0.01),with a more pronounced effect observed in the high-dose group.Conclusions Cro has a preventive and thera-peutic effect on radiation-induced intestinal injury,and its mechanism is related to anti-inflammation,anti-oxi-dation,improvement of intestinal barrier function,pro-motion of intestinal stem cell regeneration,enhance-ment of Nrf2/HO-1 signaling and reduction of NF-κB signaling activity.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.

Objective:To evaluate the efficacy and safety of radiotherapy combined with sintilimab and bevacizumab (anti-angiogenic agent) in patients with unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 80 patients with unresectable advanced HCC admitted to Shanghai Mengchao Cancer Hospital from January 2021 to September 2023 were retrospectively analyzed. All patients were divided into two groups based on treatment regimens: the systemic therapy group ( n=41) receiving sintilimab combined with bevacizumab, and combined radiotherapy group ( n=39) receiving radiotherapy plus sintilimab and bevacizumab. Efficacy was evaluated using the response evaluation criteria in solid tumors (RECIST) 1.1 version and modified RECIST for HCC. Treatment-related adverse events (TRAE) were assessed by the common terminology criteria for adverse events (CTCAE) 4.03 version. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and TRAE. Independent sample t-test was used for normally distributed quantitative data, and Chi-square test for qualitative data. Survival analysis was performed via Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression models were applied to analyze prognostic factors. Results:In terms of efficacy, no patient obtained complete response (CR) in the systemic therapy group, while 2 cases achieved CR in the combined radiotherapy group. The ORR was 22% (9/41) in the systemic therapy group and 59% (23/39) in the combined radiotherapy group ( P=0.001). The DCR was 85% (35/41) and 97% (38/39) in the two groups ( P=0.130), with the incidence of progressive disease of 15% (6/41) and 3% (1/39) ( P=0.130), respectively. The median PFS was 8.0 months (95% CI=6.8-9.2 months) in the combined radiotherapy group and 4.4 months (95% CI=4.1-4.7 months) in the systemic therapy group ( P=0.002). The median OS was 19.0 months (95% CI=15.5-22.5 months) in the combined radiotherapy group and 12.5 months (95% CI=9.4-15.6 months) in the systemic therapy group ( P=0.006). Radiotherapy was an independent protective factor for both PFS ( HR=0.474, 95% CI=0.289-0.778, P=0.003) and OS ( HR=0.403, 95% CI=0.218-0.744, P=0.004). The number of tumors >3 was an independent risk factor for both PFS ( HR=2.658, 95% CI=1.485-4.755, P=0.001) and OS ( HR=3.245, 95% CI=1.773-5.939, P=0.001). There was no significant difference in TRAE between two groups ( P > 0.05). Conclusions:Radiotherapy combined with sintilimab and bevacizumab shows high efficacy and acceptable safety in patients with unresectable advanced HCC.