Objective:To investigate the clinical efficacy of liquid nitrogen cryopreservation and reimplantation versus allograft reconstruction in patients underwent resection of primary malignant bone tumors of the long bones of the extremities.Methods:A retrospective analysis was conducted on 144 patients who underwent resection of primary malignant bone tumors of the long bones of the extremities followed by either liquid nitrogen cryopreservation and reimplantation or massive allografts reconstruction at the Beijing Jishuitan Hospital affiliated with Capital Medical University from January 2012 to July 2023. The study included 82 males and 62 females, with an average age of 23.8±12.3 years (range, 6-64 years). Patients were divided into two groups based on the reconstruction method: the cryopreservation and reimplantation group (72 cases) and the allograft group (72 cases). The following outcomes were recorded during follow-up: local tumor recurrence, bone union, union time, graft survival, and reasons for graft removal. Graft-related complications were recorded using the modified Henderson classification system of the International Limb Salvage Association. Limb function was assessed at the last follow-up using the Musculoskeletal Tumor Society score (MSTS-93).Results:All patients completed surgery and were followed up for a mean of 60.2±32.1 months (range, 12-149 months). At the last follow-up, 24 patients were dead from the tumor, 16 patients survived with the tumor (2 cases of local recurrence and 14 cases of distant metastasis), and 104 patients survived without the tumor. The bone union rate and union time in cryopreservation and reimplantation group were 90% (65/72) and 9.6±4.8 months, respectively, which was significantly superior to those in allograft group [68% (49/72) and 15.9±6.7 months, P<0.05]. The 5-year overall graft survival rate was 86.8% [95% CI (80.1%, 95.7%)] in cryopreservation and reimplantation group, higher than 73.2% [95% CI(68.4%, 84.5%)] in allograft group significantly (χ 2=7.122, P=0.017). The rates of graft removal due to non-union and infection in the cryopreservation and reimplantation group were 0% (0/72) and 1.4% (1/72), respectively, which were significantly lower than those in the allograft group [5.6% (4/72) and 9.7% (7/72), P<0.05]. Overall, 48.6% (70/144) of patients experienced at least one graft-related complication, with a complication rate of 33.3% in cryopreservation and reimplantation group, lower than the 61.1% in allograft group significantly (χ 2=11.146, P<0.001). The complications with the highest incidence rate were nonunion (20.8%, 30/144), followed by structural failure (17.4%, 25/144), tumor progression (10.4%, 15/144), infection (10.4%, 15/144), and soft tissue failure (5.6%, 8/144). The incidence rates of the atrophic non-union and the structural failure of grafts were 9.7% (7/72) and 1.4% (1/72) respectively in the cryopreservation and reimplantation group, which were significantly lower compared to the allograft group [29.2% (21/72) and 13.9% (10/72), P<0.05]. At the last follow-up, the MSTS-93 score was 89.7%±8.3% in the cryopreservation and reimplantation group, and 87.6%±7.5% in the allograft group, with no statistically significant difference ( t=0.326, P=0.542). Conclusion:Compared with allograft reconstruction, autologous inactivated bone grafting demonstrated superior bone union efficiency and fewer complications, it may be considered for reconstruction in cases whose tumor bone is not severely osteolytic or pathologically fractured.

Objective:To evaluated the efficacy and safety of eltrombopag in patients with systemic lupus erythematosus (SLE)-related refractory immune thrombocytopenia (ITP).Methods:Nine patients with severe SLE-associated refractory ITP were recruited the People's Hospital of Xinjiang Uygur Automomous Region from Septermber 2021 to February 2024 and received eltrombopag 50 mg orally daily for 1 month; basic patient information, platelet counts, other laboratory parameters and adverse events were recorded. Normally distributed continuous data were expressed as mean±standard deviation ( Mean±SD) and compared using paried samples t-test; non-normally distributed data were presented as median (interquartile range) [ M( Q1, Q3)]; categorical variables were described as n (%). Results:Eight participants (88.9%) completed the study, and at 1 month, five patients showed significant improvement in subcutaneous bleeding and erythema of the skin and mucous membranes, and three patients showed significant relief of joint and muscle involvement, and the patients′ platelet counts were (16.9±9.6)×10 9/L before treatment and increased to (114.0±53.9)×10 9/L. Differences in platelet levels before and after treatment in intergroup comparisons ( t=-4.881 , P=0.002), of which 4 patients achieved complete remission of platelet involvement, 3 patients achieved partial remission of platelet involvement, 4 cases were significantly efficacious and 3 cases efficacious. Follow-up data showed that platelet counts remained normal with no significant adverse events and one patient discontinued the study after 2 weeks of eltrombopag due to abnormal blood counts. Conclusion:Eltrombopag may be a promising new option for patients with SLE-associated refractory ITP with satisfactory remission rates, but large sample studies are needed for validation.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To investigate the clinical efficacy of liquid nitrogen cryopreservation and reimplantation versus allograft reconstruction in patients underwent resection of primary malignant bone tumors of the long bones of the extremities.Methods:A retrospective analysis was conducted on 144 patients who underwent resection of primary malignant bone tumors of the long bones of the extremities followed by either liquid nitrogen cryopreservation and reimplantation or massive allografts reconstruction at the Beijing Jishuitan Hospital affiliated with Capital Medical University from January 2012 to July 2023. The study included 82 males and 62 females, with an average age of 23.8±12.3 years (range, 6-64 years). Patients were divided into two groups based on the reconstruction method: the cryopreservation and reimplantation group (72 cases) and the allograft group (72 cases). The following outcomes were recorded during follow-up: local tumor recurrence, bone union, union time, graft survival, and reasons for graft removal. Graft-related complications were recorded using the modified Henderson classification system of the International Limb Salvage Association. Limb function was assessed at the last follow-up using the Musculoskeletal Tumor Society score (MSTS-93).Results:All patients completed surgery and were followed up for a mean of 60.2±32.1 months (range, 12-149 months). At the last follow-up, 24 patients were dead from the tumor, 16 patients survived with the tumor (2 cases of local recurrence and 14 cases of distant metastasis), and 104 patients survived without the tumor. The bone union rate and union time in cryopreservation and reimplantation group were 90% (65/72) and 9.6±4.8 months, respectively, which was significantly superior to those in allograft group [68% (49/72) and 15.9±6.7 months, P<0.05]. The 5-year overall graft survival rate was 86.8% [95% CI (80.1%, 95.7%)] in cryopreservation and reimplantation group, higher than 73.2% [95% CI(68.4%, 84.5%)] in allograft group significantly (χ 2=7.122, P=0.017). The rates of graft removal due to non-union and infection in the cryopreservation and reimplantation group were 0% (0/72) and 1.4% (1/72), respectively, which were significantly lower than those in the allograft group [5.6% (4/72) and 9.7% (7/72), P<0.05]. Overall, 48.6% (70/144) of patients experienced at least one graft-related complication, with a complication rate of 33.3% in cryopreservation and reimplantation group, lower than the 61.1% in allograft group significantly (χ 2=11.146, P<0.001). The complications with the highest incidence rate were nonunion (20.8%, 30/144), followed by structural failure (17.4%, 25/144), tumor progression (10.4%, 15/144), infection (10.4%, 15/144), and soft tissue failure (5.6%, 8/144). The incidence rates of the atrophic non-union and the structural failure of grafts were 9.7% (7/72) and 1.4% (1/72) respectively in the cryopreservation and reimplantation group, which were significantly lower compared to the allograft group [29.2% (21/72) and 13.9% (10/72), P<0.05]. At the last follow-up, the MSTS-93 score was 89.7%±8.3% in the cryopreservation and reimplantation group, and 87.6%±7.5% in the allograft group, with no statistically significant difference ( t=0.326, P=0.542). Conclusion:Compared with allograft reconstruction, autologous inactivated bone grafting demonstrated superior bone union efficiency and fewer complications, it may be considered for reconstruction in cases whose tumor bone is not severely osteolytic or pathologically fractured.

Objective:To evaluated the efficacy and safety of eltrombopag in patients with systemic lupus erythematosus (SLE)-related refractory immune thrombocytopenia (ITP).Methods:Nine patients with severe SLE-associated refractory ITP were recruited the People's Hospital of Xinjiang Uygur Automomous Region from Septermber 2021 to February 2024 and received eltrombopag 50 mg orally daily for 1 month; basic patient information, platelet counts, other laboratory parameters and adverse events were recorded. Normally distributed continuous data were expressed as mean±standard deviation ( Mean±SD) and compared using paried samples t-test; non-normally distributed data were presented as median (interquartile range) [ M( Q1, Q3)]; categorical variables were described as n (%). Results:Eight participants (88.9%) completed the study, and at 1 month, five patients showed significant improvement in subcutaneous bleeding and erythema of the skin and mucous membranes, and three patients showed significant relief of joint and muscle involvement, and the patients′ platelet counts were (16.9±9.6)×10 9/L before treatment and increased to (114.0±53.9)×10 9/L. Differences in platelet levels before and after treatment in intergroup comparisons ( t=-4.881 , P=0.002), of which 4 patients achieved complete remission of platelet involvement, 3 patients achieved partial remission of platelet involvement, 4 cases were significantly efficacious and 3 cases efficacious. Follow-up data showed that platelet counts remained normal with no significant adverse events and one patient discontinued the study after 2 weeks of eltrombopag due to abnormal blood counts. Conclusion:Eltrombopag may be a promising new option for patients with SLE-associated refractory ITP with satisfactory remission rates, but large sample studies are needed for validation.

To explore the clinical outcomes of fertility-sparing treatment (FST) in patients with POLE-mutated endometrioid carcinoma (EEC). A total of 9 EEC patients who received FST and were classified to the POLE-mutated subtype in Peking University People's Hospital from April 2020 to October 2023, were retrospectively collected. Clinical and pathological data were analyzed to describe the outcomes of FST in patients with POLE-mutated EEC.A total of 9 patients with EEC including 6 cases with well-differentiated (G1) and 3 cases with moderately-differentiated (G2). The average age was 34.8±2.1 years. POLE mutation sites were P286R (5 cases), V411L (2 cases), L424I (1 cases), and S459F (1 cases), respectively.The median follow-up time was 16 months (9–41 months). The complete response (CR) rate was 88.9% (8/9), with a median time to CR of 5.5 months (3–18 months). The partial response (PR) rate was 11.1% (1/9). The relapse rate was 50.0% (4/8), with a median recurrence time of 9.5 months (5–25 months). Of these, 75% (3/4) underwent secondary FST, with all achieving CR again (3/3). Three of 5 who were out-of-indication patients achieved CR by individual therapy. FST in patients with POLE-mutated EEC achieve a CR rate of 88.9% in this study, the largest number of retrievable reports. In certain patients who are out-ofindication, individualized treatment may also result in remission. However, unlike surgical patients, some patients experience disease recurrence and whether POLE-mutated EEC is sensitive to conventional therapy in FST is controversial given its pathogenesis.

Chemoresistance to 5-fluorouracil (5-FU) is a significant challenge in treating colorectal cancer (CRC). Novel combined regimens to thwart chemoresistance are therefore urgently needed. Herein, we demonstrated that the combination of Avenanthramide A (AVN A) and 5-FU has significant therapeutic advantages against CRC. Mechanistically, AVN A directly binds to the S198 site of the histone lysine demethylase KDM4C to promote its degradation, which subsequently fosters H3K9me3 occupancy on the MIR17HG promoter to block its transcription and derepress Bim expression. AVN A enhanced the therapeutic efficacy of 5-FU via impairing the KDM4C/MIR17HG/GSK-3β negative feedback loop. Importantly, the clinical correlation of the KDM4C/MIR17HG/Bim signaling axis with 5-FU response was validated in the refractory CRC patients. We provide evidence for the enhanced effectiveness of 5-FU when combined with AVN A in chemoresistant xenografts, CRC organoids, and Apc ^Min/+ mouse model. Additionally, AVN A mitigated the systemic adverse effects of 5-FU. Overall, our findings demonstrate that combinatorial therapy with AVN A and 5-FU represents an appealing opportunity and highlights KDM4C/MIR17HG/GSK-3β negative feedback loop which confers therapeutically exploitable vulnerability to chemo-refractory CRC patients.

Objective:To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes.Methods:A total of 258 patients diagnosed EC undergoing surgery in Peking University People′s Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative.Results:(1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences ( χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis ( HR=6.93, 95% CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression ( HR=0.04, 95% CI: 0.01-0.14; P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions:LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

Objective:To analyze the prognostic factors and the influence of surgical margin to prognosis.Methods:A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models.Results:There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection ( P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection ( P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection ( P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions:The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.