Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective To explore the effects of fecal microbiota transplantation(FMT)on oxalate metabolism and renal protection in rats fed a high oxalate diet.Methods Twenty-four male SD rats were randomly divided into four groups:SC,SC+FMT,OD+PBS and OD+FMT.The SC group was set as the control group and was fed standard rat chow.The OD+PBS group and OD+FMT group were fed a diet containing 5%oxalate.Starting from day 14,the OD+PBS group,OD+FMT group and SC+FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days.The 24-hour urine,feces,and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers.Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin,ACE,and OPN.Results The fecal microbiota transplantation altered the gut microbiota of rats.The gut microbiota of the SC+FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs.Compared to the OD+PBS group,the OD+FMT group exhibited significant reductions in the urinary oxalate,urinary urea,uric acid,urinary creatinine,serum urea nitrogen/creati-nine,and serum uric acid.Furthermore,after FMT treatment,the OD+FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD+PBS group;similar results were obtained from immunohistochemistry.Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut,particularly the oxalate-degrading bacteria represented by Muribaculaceae.The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate,indicating the protective effect of fecal microbiota transplantation on the rat kidneys.

Objective:To investigate the safety and efficacy of four-hook needle combined with holographic image in robot-assisted partial nephrectomy for completely intrarenal tumors.Methods:The clinical data of 8 patients with completely intrarenal tumors treated by robot-assisted partial nephrectomy with four-hook needle combined with holographic image admitted to General Hospital of Central Theater Command from October 2023 to December 2023 were retrospectively analyzed. There were 6 males and 2 females, with average age of (44.5±12.0) years old. Tumors of 6 cases were in the left side and 2 cases in the right side. The maximum diameter of the tumor was (23.2±8.1) mm. The R. E.N.A.L. score was (9.0±1.4). The preoperative serum creatinine (Scr) was (73.1±14.7) μmol/L. CT-guided four-hook needle was used to locate the edge of completely intrarenal tumor before surgery. During the operation, the tumor was precisely resected under the guidance of hologram and four-hook needle. Perioperative data of patients were collected and analyzed.Results:All the tumor were successfully resected under the guidance of four-hook needle and hologram without conversion to radical nephrectomy or open surgery. The mean operative time was (117.0±14.5) min, the mean hot ischemia time was (20.2±5.1) min, the mean intraoperative blood loss was (75.0±17.3) ml, and the average hospitalization time was (9.5±1.3) days.The one week postoperative Scr was (73.2±14.8) μmol/L, which had no significant difference with that of before operation ( P=0.952). None of them received blood transfusion. The pathology results of 8 patients were clear cell renal cell carcinoma, and the surgical margins were negative. Conclusions:For completely intrarenal tumors, the four-hook needle combined with the hologram can guide the surgeon to quickly locate the tumor, accurately resect the tumor, reduce perioperative complications, and is safe and effective.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.

Objective:To explore the effect of fecal microbiota transplantation (FMT) on the formation of renal calcium oxalate crystals in SD rats induced by oxalate mixed diet.Methods:Six male guinea pigs were fed with standard guinea pig chow for 1 month and then given a 5% oxalate diet for 14 d. The guinea pigs on the standard chow were labeled as the standard chow guinea pig (GSC group) and those on the high oxalate diet for 14 d were labeled as the guinea pig group on the high oxalate diet (GOD group). The feces of guinea pigs in the GSC and GOD groups were collected using metabolic cages. Twenty-four male SD rats were randomly divided into standard chow (SC) group, oxalate diet(OD)+ phosphate buffered saline gavage group (OD+ PBS group), OD+ FMT group and SC+ FMT group. Among them, the SC group and SC+ FMT group were fed with standard chow. The OD+ PBS group and OD+ FMT group were fed with 5% oxalate content chow. The OD+ FMT and SC+ FMT groups were given GOD group guinea pig fecal filtrate gavage for 7 days. The 24 h urine and feces of rats in each group were collected, and the intestinal microbiota of rats and guinea pigs were detected by 16sRNA detection. The urinary oxalate excretion was detected by high performance liquid chromatography. The rats and kidneys were weighed and the renal index was calculated. HE staining was used to observe the histological morphological changes of rat kidney tissue, the calcium oxalate crystal deposition in renal tissues was detected by Pizzolato staining.Results:The relative abundance of bacteria from a total of 11 families, including Muribaculaceae family and Bifidobacteriaceae family, was significantly increased in the intestinal tract of guinea pigs (GOD) from the high oxalate diet group compared to guinea pigs (GSC) from the standard chow group. The microbial diversity of the intestinal microbiota of the rats in the OD+ PBS group was reduced compared to the SC group, and the microbial diversity of the intestinal microbiota of the rats in the OD+ FMT group was restored compared to the OD+ PBS group. When given a standard chow, the intestinal microbiota of rats receiving FMT deviated from that of normal rats and was more similar to that of guinea pigs fed a high oxalate diet. In the OD+ FMT group, bacteria from a total of 18 families, including Muribaculaceae family, Erysipelotrichaceae family and Bifidobacteriaceae family, were significantly enriched, and FMT activated the intestinal microbial network represented by bacteria from Muribaculaceae family. The renal index of rats in the OD+ PBS group was significantly increased compared to the SC group (7.63±0.67 vs. 6.12±0.53, P<0.05), whereas the renal index of rats in the OD+ FMT group was significantly decreased in comparison to the OD+ PBS group (6.53±0.64 vs. 7.63±0.67, P<0.05). Urinary oxalate excretion of rats in the SC group, the OD+ PBS group, and the OD+ FMT group were (0.61±0.05), (0.89±0.04) and (0.72±0.04) μmol/ml, respectively. In the rats of the SC group no calcium oxalate crystals were seen in the kidney (0 score) and more calcium oxalate crystals were detected in the OD+ PBS group (4.83±0.41 score). The OD+ FMT group showed significantly lower calcium oxalate crystallization scores (3.17 ± 0.75 score, P<0.01) compared to the OD+ PBS group. Conclusions:FMT activated the microbial network represented by bacteria from the family Muribaculaceae in the rat intestine, significantly reduced urinary oxalate excretion and renal calcium oxalate crystal deposition in rats on a high oxalate diet.

[This corrects the article DOI: 10.1016/j.chmed.2022.08.005.].

Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

Objective:Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics.Methods:A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system.Results:In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis ( P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS ( P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old ( OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 ( OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow ( OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation ( OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion:Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.

Objective:To investigate the clinical features, the key point of diagnosis and treatment methods of X-linked hyper-IgM syndrome (XHIGM).Methods:The clinical characteristics and laboratory data of a patient aged 23 years who was diagnosed as XHIGM complicated with T-cell large granular lymphocytic leukemia (TLGLL) in Institute of Hematology & Blood Diseases Hospital in March 2020 were analyzed retrospectively, and the literatures were reviewed.Results:This male patient presented with recurrent infection when he was 17 years old, and was found neutropenia, anemia accompanied by obvious splenomegaly, lower level of IgG and IgA after the visit. The level of IgM was lower than the normal level and the typical XHIGM was manifested with the normal or increased level of IgM, however CD40L homozygous mutation (chromosome: chrX; location: 135730438; variation of amino acid: NM_000074:exon1:c.31C>T:p.R11X; nonsense mutation) was confirmed by next generation sequencing. CD40L heterozygous mutation was detected in his mother, but it was not in his father. The patient was diagnosed as XHIGM. Anemia and neutropenia were alleviated after splenectomy in the patient, who was diagnosed as T-cell large granular lymphocyte elevation and clonal proliferation by flow cytometry, TCR gene rearrangement positive and bone marrow histopathological immunohistochemistry results because of the increasing leukocyte. The patient was eventually diagnosed as XHIGM complicated with T-LGLL.Conclusions:A small number of patients with XHIGM may develop symptoms in adulthood and may present with atypical clinical features of significant reduction in IgG, IgA, and IgM. The confirmed diagnosis of XHIGM is established by identification of CD40L gene mutation. XHIGM gene screening is required in male patients with recurrent infection, IgG level lower than normal and neutropenia. A few XHIGM patients are complicated with T-LGLL.