[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

[Association of triglyceride glucose index and risk of incident hypertension: a prospective cohort study].

Objective: To explore the relationship between the triglyceride glucose (TyG) index and the risk of developing hypertension among rural Chinese adults. Methods: A prospective cohort study was conducted from 2007 to 2008, involving 20 194 adults selected through random cluster sampling from a rural community in Luoyang City, Henan Province. Follow-ups were carried out in 2013-2014 and 2018-2020. After excluding participants with hypertension at baseline, those with missing TyG index data, individuals who passed away during follow-up, and those with incomplete hypertension status at the second visit, 9 802 participants were included in the analysis. Baseline and follow-up assessments included questionnaire interviews, physical measurements (including blood pressure), and blood sample collection for fasting lipid and glucose levels. Participants were divided into four groups according to TyG index quartiles, and a modified Poisson regression model was utilized to assess the association between TyG index quartiles and hypertension risk. Results: The study cohort comprised 9 802 participants with a median age of 48 (39, 57) years, including 3 803 males (38.80%). Participants were distributed across TyG index quartiles as follows: TyG<8.2 group (2 224 individuals), TyG 8.2-8.5 group (2 653 individuals), TyG 8.6-8.9 (2 441 individuals), and TyG≥9.0 (2 484 individuals). Over a follow-up period of (11.1±1.3) years, 3 378 subjects developed hypertension, resulting in a cumulative incidence of 34.46% (3 378/9 802). The risk of hypertension increased with higher TyG index quartiles (Ptrend<0.05). Compared to the TyG<8.2, the TyG 8.2-8.5 (RR=1.11, 95%CI 1.01-1.22, P=0.023), TyG 8.6-8.9 (RR=1.16, 95%CI 1.06-1.27, P=0.023), and TyG≥9.0 (RR=1.20, 95%CI 1.10-1.31, P=0.023) exhibited increased hypertension risk after adjusting for age, gender, educational level, and other potential confounders. Subgroup analyses based on gender and age at baseline yielded results consistent with the main analysis. Conclusions: The TyG index is positively correlated with the risk of developing hypertension in the rural adult population.

[Clinical outcome of posterior lumbar interbody fusion combined with Ponte osteotomy for reconstruction of coronal sagittal plane balance in degenerative scoliosis].

Objective: To evaluate the clinical efficacy of posterior lumbar interbody fusion combined with Ponte osteotomy in the treatment of patients with degenerative scoliosis. Methods: The medical records and imaging data of degenerative scoliosis in department of orthopedics, Peking Union Medical College Hospital from 2013 to 2022 were retrospectively collected, and the shortest follow-up time was 1 year. A total of 38 patients were included, including 13 males and 25 females, aged 50-87(65.6±10.9) years old.The follow-up was12-119(43±20) months. Standing position full spine anteroposterior lateral X-ray examinations were performed on all patients preoperatively, postoperatively, and at latest follow-up. The length of hospital stay, complications, operation time, blood loss, instrumented segment, fusion segmen were recorded. The clinical scores and coronasagittal imaging indicators at three time points were compared. Results: The operation time was (274.5±70.5)min, and intraoperative blood loss was (619.2±93.5)ml. The coronal vertical axis was improved from (2.9±1.8)cm preoperatively to (1.2±1.0)cm postoperatively. The preoperative coronal Cobb angle was 16.6°±9.9° and the immediate postoperative correction was 6.4°±4.0°(t=-6.83, P<0.001). The difference was statistically significant (t=-6.12, P<0.001). The coronal Cobb Angle at the last follow-up was 5.7°±3.7°, and there was no significant orthopaedic loss at the last follow-up (t=-6.12, P<0.001).The sagittal vertical axis decreased from (5.6±3.9)cm preoperatively to (3.2±2.5) cm immediately after operation (t=-6.83,P<0.001), and was well maintained at the last follow-up[(2.7±1.8) cm,t=-7.77,P<0.001]. Lumbar lordosis increased from 21.8°±10.2° preoperatively to 35.8°±8.3° postoperatively(t=12.01, P<0.001)and 40.1°±8.6° at last follow-up(t=-10.21, P<0.001). Oswestry disability score (ODI score), visual analogue score (VAS) low back pain score and VAS leg pain score were also lower after surgery than before surgery (all P<0.05). Conclusion: Posterior lumbar interbody fusion combined with Ponte osteotomy can significantly improve the coronal and sagittal plane deformity and postoperative functional score in adult patients with degenerative scoliosis.

Cardiac MRI for clinical dilated cardiomyopathy: Improved diagnostic power via combined T1, T2, and ECV.

INTRODUCTION: Early diagnosis of patients with dilated cardiomyopathy (DCM) remains challenging. Cardiac MR can correlate myocardial changes with their pathological basis. There have been some previous studies on the effect of T1 mapping in DCM, but there is limited data on the incremental value of T2 mapping for DCM in routine clinical practice. This study will examine whether the combination of MRI T1 and T2 mapping offers greater advantages in the diagnosis of DCM. METHODS: The study included 28 patients with DCM and 21 healthy controls. CMR evaluation included late gadolinium enhancement (LGE), T1 mapping, extracellular volume (ECV) fraction and T2 mapping. The DCM group was divided into LGE (+) and LGE (-) subgroups. The main modes of LGE are subendocardial, midwall, subepicardial, or transmural. T1 values, T2 values, and ECV in the 16 segments myocardial levels were measured by post-processing software. Student's t-tests or Mann-Whitney U test was used to compare between two groups, and one-way ANOVA or Kruskal-Wallis H test was used to compare between multiple groups, with p values corrected by Bonferroni. The difference was considered statistically significant at P < 0.05. ROC curve analysis was used to compare the area under the curve (AUC) of each index and its combined value, and the cut-off value, sensitivity and specificity were determined by Jordan's index. RESULTS: Mean native myocardial T1, ECV and T2 were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). The best cut-off values for T1, T2 and ECV to discriminate DCM from controls were 1184 ms, 40.9 ms and 29.2%, respectively. The AUC of T1, ECV and T2 were 0.87, 0.89, and 0.83, respectively. The combined AUC of the three values was 0.96. CONCLUSION: Native T1 value and ECV overcome some of the limitations of LGE, and the T2 helps to understand the extent of myocardial damage. The combination of T1 and T2 mapping techniques can reveal fibrotic and oedematous changes in the early stages of DCM, providing a more comprehensive assessment of DCM and better guidance for individualised clinical management of patients. IMPLICATIONS FOR PRACTICE: We suggest that the addition of T2 mapping to the routine CMR examination of patients with suspected DCM, and the combined assessment of T1mapping and T2 mapping can provide complementary information about the disease and improve the early diagnosis of DCM.

[Predictive value of cardiac magnetic resonance imaging for adverse left ventricular remodeling after acute ST-segment elevation myocardial infarction].

OBJECTIVE: To assess the value of cardiac magnetic resonance (CMR) imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively analyzed the clinical data and serial CMR (cine and LGE sequences) images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention (PCI), including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling, defined as an increase of left ventricular end-systolic volume (LVESV) over 15% at the second CMR compared to the initial CMR. The CMR images were analyzed for LV volume, infarct characteristics, and global and infarct zone myocardial function. The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods. RESULTS: The initial CMR showed no significant differences in LV volume or LV ejection fraction (LVEF) between the two groups, but the infarct mass and microvascular obstructive (MVO) mass were significantly greater in adverse LV remodeling group (P < 0.05). Myocardial injury and cardiac function of the patients recovered over time in both groups. At the second CMR, the patients with adverse LV remodeling showed a significantly lower LVEF, a larger left ventricular end-systolic volume index (LVESVI) and a greater extent of infarct mass (P < 0.001) with lower global peak strains and strain rates in the radial, circumferential, and longitudinal directions (P < 0.05), infarct zone peak strains in the 3 directions, and infarct zone peak radial and circumferential strain rates (P < 0.05). The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass (AUC=0.793, 95% CI: 0.693-0.873; cut-off value: 30.67%), radial diastolic peak strain rate (AUC=0.645, 95% CI: 0.534-0.745; cut-off value: 0.58%), and RAAS inhibitor (AUC= 0.699, 95% CI: 0.590-0.793). CONCLUSION: The extent of infarct mass, peak radial diastolic strain rate, and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant and immune responses of lactating donkeys.

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 weeks for adaptation, and 8 weeks for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including dry matter intake, milking yield, estimated milk yield, solids-corrected milk, energy-corrected milk, milk fat yield, milk protein yield, milk lactose yield, milk total solids yield, and milk solid not fat yield. The digestibility of dry matter, crude protein, acid detergent fiber, and neutral detergent fiber was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of immunoglobulin A, immunoglobulin G, and immunoglobulin M, the activities of the superoxide dismutase, catalase and total antioxidant capacity in the serum. AOCP decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites L-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, LysoPC (18:0), LysoPC (18:1(9Z), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.

Brassica napus BnaA09.MYB52 enhances seed coat mucilage accumulation and tolerance to osmotic stress during seed germination in Arabidopsis thaliana.

Seed coat mucilage plays an important role in promoting seed germination under adversity. Previous studies have shown that Arabidopsis thaliana MYB52 (AtMYB52) can positively regulate seed coat mucilage accumulation. However, the role of Brassica napus MYB52 (BnaMYB52) in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination remains largely unknown. We cloned the BnaA09.MYB52 coding domain sequence from B. napus cv ZS11, identified its conserved protein domains and elucidated its relationship with homologues from a range of plant species. Transgenic plants overexpressing BnaA09.MYB52 in the A. thaliana myb52-1 mutant were generated through Agrobacterium-mediated transformation and used to assess the possible roles of BnaA09.MYB52 in accumulation of seed coat mucilage and tolerance to osmotic stress during seed germination. Subcellular localization and transcriptional activity assays demonstrated that BnaA09.MYB52 functions as a transcription factor. RT-qPCR results indicate that BnaA09.MYB52 is predominantly expressed in roots and developing seeds of B. napus cv ZS11. Introduction of BnaA09.MYB52 into myb52-1 restored thinner seed coat mucilage in this mutant to levels in the wild type. Consistently, expression levels of three key genes participating in mucilage formation in developing seeds of myb52-1 were also restored to wild type levels by overexpressing BnaA09.MYB52. Furthermore, BnaA09.MYB52 was induced by osmotic stress during seed germination in B. napus, and ectopic expression of BnaA09.MYB52 successfully corrected sensitivity of the myb52-1 mutant to osmotic stress during seed germination. These findings enhance our understanding of the functions of BnaA09.MYB52 and provide a novel strategy for future B. napus breeding.

[Prognostic nutritional index application value for acute-on-chronic liver failure co-infection].

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.

[L-DEP regimen salvage therapy for refractory primary hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection in 4 children].

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

The changes in abdominal wall muscles following incisional hernia wall reconstruction.

PURPOSE: The objective of incisional hernia surgery is to achieve the restoration of abdominal wall anatomical and physiological functions. This study aims to investigate the impact of abdominal wall reconstruction on abdominal muscle alterations by measuring the preoperative and postoperative changes in abdominal wall muscles in patients undergoing incisional hernia repair. METHODS: For patients undergoing open incisional hernia abdominal wall reconstruction, preoperative and postoperative abdominal CT scans were analyzed at a minimum of 3 months post-surgery. 3D Slicer software was utilized for measuring preoperative and postoperative changes in abdominal cavity volume, abdominal muscle volume, as well as muscle volume, cross-sectional area, and abdominal circumference at specific levels. The acquired data were subjected to statistical analysis using SPSS software. RESULTS: A total of 40 patients meeting the inclusion criteria underwent open incisional hernia repair surgery. Some of these patients required component separation technique (CST) due to the larger size of the hernia sac. The abdominal muscles surrounding the hernia ring were defined as the "damaged group," while the remaining abdominal muscles were defined as the "undamaged group." Measurements revealed a significant increase in the volume of rectus abdominis, external oblique, internal oblique, and transversus abdominis muscles in the damaged group. Similarly, there was a corresponding increase in the volume of rectus abdominis, external oblique, internal oblique, and transversus abdominis muscles in the undamaged group. CONCLUSIONS: After abdominal wall reconstruction in incisional hernia patients, not only is their anatomical structure restored, but the overall biomechanical integrity of the abdominal wall is also repaired. The damaged muscles are subjected to renewed loading, leading to the reversal of disuse atrophy and an increase in muscle volume.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery].

Objective: To investigate the effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery. Methods: This study was a cross-sectional study. Patients who underwent surgery for papillary thyroid cancer (PTC) at the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University between January 2022 and September 2023 were included. All patients underwent thyroid lobectomy or total resection, and central lymph node dissection was performed at the same time. During the operation, tracing injection of mitoxantrone hydrochloride and 785 nm and 660 nm dual fluorescence imaging technique were used to measure the fluorescence intensity (FI) of parathyroid glands, central lymph nodes and background. After correcting to obtain the standardized FI, the paired t-test was used to compare the standardized FI of the parathyroid glands and central lymph nodes, and the Spearman's rank correlation analysis was used to analyze the relationship between the standardized FI and various clinical indicators. Results: The study included 30 patients (8 males and 22 females), with a mean age of (41.8±10.4) years. A total of 76 parathyroid glands and 234 central lymph nodes were identified under dual fluorescence imaging, and the standardized FI of parathyroid glands was less than that of central lymph nodes (44.7±16.8 vs 99.5±28.4, P<0.001). The visualization rate, false rate and miscut rate of parathyroid glands under 785 nm wavelength excitation light were 98.7% (76/77), 0 (0/77) and 1.3% (1/77), respectively (one case with no visualization and miscutting parathyroid gland was the encapsulated type). The visualization rate of central lymph nodes under 660 nm wavelength excitation light was 98.7% (234/237). There was no significant correlation between FI and clinical indicators such as gender, age, height, weight, body mass index, preoperative thyroid stimulating hormone, thyroglobulin antibody, thyroid microsomal antibody, serum calcium, parathyroid hormone level and surgical procedure (all P>0.05). Conclusion: Dual fluorescence imaging of central lymph nodes and parathyroid glands can improve the ability to identify parathyroid gland while assisting central lymph node dissection.

The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

Estimation and projection of the burden of hearing loss in China: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The comprehensive description of hearing loss in China and the shifting pattern remain unclear. We conducted the study to estimate the burden of hearing loss in China and project the trends from 2020 to 2034. STUDY DESIGN AND METHOD: Data on the disease burden of hearing loss were extracted from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of hearing loss burden were made until 2034 using Bayesian age-period-cohort analysis. RESULTS: In China, prevalent cases of hearing loss increased from 224.4 million in 1990 to 426.5 million in 2019, representing an increase of 90.1 %. The age-standardized prevalence rate of hearing loss ranged from 22,592.8/100,000 in 1990-22,612.4/100,000 in 2019, with an EAPC of 0.003 %, representing a stable trend. Of the category of hearing loss, mild hearing loss accounted for the highest proportion, with 331.4 million people. More than 95 million people had moderate-to-complete hearing loss. Moreover, hearing loss was mostly attributable to age-related and other factors for adults and otitis media for children younger than 10 years. Based on the projection results, there will be 561 million people (40.1 % of the total population) have hearing loss by 2034. CONCLUSIONS: The prevalent cases of hearing loss in China substantially increased over the last 30 years. Over two in five Chinese people will have hearing loss by 2034, thus suggesting more solutions should be established to reduce the burden of hearing loss.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.