Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Objective:To investigate the correlation between lymphocyte-monocyte ratio (LMR) and long-term prognosis after distal cholangiocarcinoma.Methods:A retrospective case-control study was conducted to analyze the clinical data of 186 patients with distal cholangiocarcinoma who underwent radical pancreaticoduodenectomy at Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2013 to December 2023. Among them, there were 109 males and 77 females, with an age of (65.4±9.4) years, ranging from 29 to 85 years. The data of preoperative peripheral blood routine examination of the patients were collected, and the patients were divided into a high LMR group(LMR>2.98, n=100) and a low LMR group(LMR≤2.98, n=86). The preoperative, intraoperative and postoperative clinical characteristics of the two groups were compared. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. Measurement data with non-normal distribution were expressed as M( Q1, Q3), and Mann-Whitney U test was used for inter-group comparison. Chi-square test was used for inter-group comparison of count data. The Cox proportional hazards regression model was used for univariate and multivariate prognostic analysis, and the Kaplan-Meier estimation method was used to create survival curves to analyze and evaluate the influencing factors of long-term prognosis after distal cholangiocarcinoma surgery. Results:Univariate analysis results showed that gender, age, BMI, history of diabetes, carcinoembryonic antigen; operation duration, intraoperative blood loss; resection margin status, degree of tumor cell differentiation, and presence of postoperative complications had no statistically significant differences in their impact on the prognosis of patients after distal cholangiocarcinoma surgery( P>0.05). In contrast, LMR, neutrophilto-lymphocyte ratio, platelet-lymphocyte ratio, albumin, total bilirubin, carbohydrate antigen 199, intraoperative blood transfusion, tumor diameter, and lymph node metastasis showed statistically significant differences in their influence on the postoperative prognosis of distal cholangiocarcinoma patients( P<0.05). Multivariate analysis results indicated that LMR≤2.98( HR=1.776, 95% CI: 1.153-2.736), CA19-9>37 U/mL( HR=1.521, 95% CI: 1.025-2.259), and lymph node metastasis( HR=1.601, 95% CI: 1.106-2.318) were independent risk factors affecting patient prognosis( P<0.05). The 1-, 3-, and 5-year cumulative survival rates in the high LMR group were 91%, 40%, and 20% respectively, while those in the low LMR group were 58.1%, 15.1%, and 8.1% respectively, with a statistically significant difference( P<0.05). Conclusion:Preoperative LMR for distal cholangiocarcinoma can suggest a long-term prognosis, and a low LMR value suggests a poor prognosis.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Objective:To investigate the impact of Tumor-Infiltrating Lymphocytes (TILs) density in the tumor stroma on the long-term prognosis of hepatocellular carcinoma (HCC) liver transplant patients meeting the Hangzhou criteria.Methods:This study is a retrospective cohort study. The clinical data of 83 patients with hepatocellular carcinoma who met the Hangzhou criteria and underwent allogeneic liver transplantation from January 2018 to December 2023 in the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University were collected and analyzed. Hematoxylin and Eosin (HE) staining was used to study the density of TILs in the resected liver grafts. Patients were divided into TILs-negative group (TILs<10%, n=31) and TILs-positive group (TILs≥10%, n=52) based on whether the TILs density exceeded 10%. Clinical and pathological characteristics were analyzed, and the significance of alpha-fetoprotein (AFP), TILs density, and microvascular invasion on the prognosis of HCC patients who met the Hangzhou criteria was studied. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared between groups using t-test. Measurement data with skewed distribution were expressed as M ( Q1, Q3) and compared using rank-sum tests. Categorical data were compared using chi-square test. Kaplan-Meier method was used to study the relationship between various observation indicators and overall survival, and survival curves were plotted. Log-rank test was used to compare the survival rates between groups, and multivariate Cox regression model was used to adjust for the distribution of risk factors between groups. Results:The preoperative AFP level in the TILs-negative group was (15.69±1.21) U/mL, and in the TILs-positive group was (12.17±0.13) U/mL, with a statistically significant difference between the two groups ( P<0.05). In the TILs-negative group, 8 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 8, 23, and 0, respectively. In the TILs-positive group, 3 cases had microvascular invasion, and the number of low, moderate, and high differentiation tumors was 2, 31, and 19, respectively. The results indicated that patients in the TILs-negative group were more likely to have microvascular invasion and poorer tumor differentiation ( P<0.05). All patients were regularly followed up, and the 1-, 2-, and 3-year survival rates in the TILs-negative group and TILs-positive group were 84.0%, 77.6%, 69.8%, and 94.7%, 91.7%, 86.6%, respectively ( P<0.01). Cox proportional hazards model indicated that microvascular invasion ( RR=4.474, 95% CI: 1.172-17.072, P=0.028) and TILs-negative status ( RR=5.081, 95% CI: 1.420-18.184, P=0.012) were independent risk factors for the long-term prognosis of HCC patients who met the Hangzhou criteria. Conclusions:Among HCC patients meeting the Hangzhou criteria, the density of TILs in the tumor stroma is related to AFP levels, tumor differentiation, and the presence of microvascular invasion. TILs-negative status indicates a poorer prognosis for these patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS)and the difference of physiological curvature between different types of scoliosis.Methods A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021.The patients were divided into normal group and scoliosis group.The normal group was composed of 179 patients,79 males and 100 females,aged 10 to 18 years old with an average of(12.84±2.10)years old,with cobb agle less than 10 degrees.The scol-iosis group was composed of 126 patients,33 males and 93 females,aged 10 to 18 years old with an average of(13.92±2.20)years old.The gender,age,Risser sign,thoracic kyphosis(TK)and lumbar lordosis(LL)in 2 groups were compared,and the TK and LL were also compared between different genders,different degrees of scoliosis and different segments of scoliosis.Re-sults The female ratio(P=0.001)and age(P＜0.001)in scoliosis group were higher than them in normal group;the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038).TK was significantly smaller in scoliosis group than in normal group(P＜0.001),but there was no significant difference in LL between the 2 groups(P=0.147).There were no significant difference in TK and LL between male and female.The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P＜0.05),but there was no significant difference in LL between mild and moderate patients(P＞0.05).The TK and LL in different segments scoliosis were not found significant difference.Conclusion The physiological curvature of thoracic and lumbar spine is independent of gender.The thoracic physiological curvature becomes smaller in AIS patients,but lumbar curvature remains unchanged.The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients,but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent.The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative an-terior spinal overgrowth,and the specific detailed mechanism needs to be further studied.

AIM: To investigate the clinical effect and stability of biological amnion membrane coverage combined with corneal bandage lens for patients with chemical burns of ocular surface.METHODS: Retrospective study. The clinical data of 49 cases(49 eyes)of patients with chemical burns of ocular surface treated in our hospital between December 2018 and August 2021 were collected. They were divided into the biological amnion membrane coverage group and the biological amnion membrane coverage combined with corneal bandage lens group according to the surgical method. The loss time of biological amniotic membrane, postoperative pain score, repair rate and time of ocular surface, visual acuity and complications were compared between the two groups.RESULTS: The ocular pain scores of the two groups were 2.208±0.758(the biological amnion membrane coverage group)and 2.063±0.800(the biological amnion membrane coverage combined with corneal bandage lens group)at 1d after surgery, respectively(P>0.05). But at the 3d and 7d after surgery, pain scores were 1.844±0.762 and 1.150±0.582, 1.684±0.820 and 0.750±0.514, respectively(all P<0.05). The loss time of biological amniotic membrane in the biological amnion membrane coverage combined with corneal bandage lens group was 10.75±2.63d, which was longer than that in the biological amnion membrane coverage group(7.60±2.22d; P<0.05). Moreover, it has better ocular surface repair effect than the biological amnion membrane coverage group. At 6mo after operation, visual acuity in the two groups was 0.30(0.10, 0.55)and 0.30(0.20, 0.58), respectively(P>0.05). Additionally, there was no differences in the complications of both groups(P>0.05).CONCLUSION:Biological amnion membrane coverage has effective treatment effects on patients with chemical burns of ocular surface, and it can delay the loss time of biological amniotic membrane, increase repair rate of ocular surface and alleviate postoperative discomfort if combined with corneal bandage lens.