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Over the last two generations, there has been a surge of interest in nonmutilating treatment for women with early breast cancer. Neoadjuvant radiation therapy, which is progressively being provided to breast cancer patients, could be used to decrease tumor burden while also providing an ability to examine treatment response. This paper aims to explore the effects of the initiation time of radiotherapy after modified adjuvant radical mastectomy on the prognosis of breast cancer. The EMR data can be used to mine hidden rules, which are of great significance for treatment and prognosis analysis. In collaboration with breast cancer, the appropriate prediction model and visualization method are selected and a visual analysis system for breast cancer group and treatment plan based on electronic medical record is constructed. Patients with multiple dimensions are reduced and clustered to form patient groups. The differences of characteristics among patient groups are intuitively displayed by using Nightingale diagram, word cloud, and time axis visualization methods. The support vector machine (SVM) model is used to predict the treatment scheme. The radiotherapy time after modified radical surgery in the two groups was within 15 weeks (observation group) and 15 weeks (routine group), respectively. The incidence of complications, local recurrence rate, progression-free survival, and quality of life scores of patients in the routine group and observation group were compared. The total incidence of complications differed significantly between the observation and routine groups. The physical function, material function, psychological function, and social function of the observation group were significantly higher than the routine group P < 0.05 . Radiotherapy within 15 weeks after modified radical mastectomy for breast cancer can not only reduce the local recurrence rate but also prolong the progression-free survival of patients, and the incidence of complications will not increase, which will greatly help improve the quality of life of patients.

Objective To systematically explore the association between pathogenic/likely pathogenic copy number variations (pCNV) and ultrasonographic anomalies and soft markers. Design Retrospective cohort study. Setting Data were obtained from multiple centers in china. Population or Sample Fetuses performed low-pass genome sequencing and ultrasonography between 2016 and 2020. Method The yields of pCNV under various ultrasonographic indications were compared with that of fetuses with no identifiable anomalies. In addition, the ultrasonographic characteristics of aneuploidy and pCNV were described in comparison with those of fetuses without chromosomal aberrations. Main Outcome Measures Yields of aneuploidy and pCNV in different ultrasonographic indications. Results Ten of the 12 ultrasonographic anomalies had significantly higher yield of pCNV, except for fetal hydrops and abnormal amniotic fluid, of which the gastrointestinal, facial, respiratory systems, and abdominal wall defect were rarely reported. Similarly, five of the 12 soft markers had significantly higher yield of pCNV, with single umbilical artery being rarely reported. Furthermore, this study reported that four duplications/deletions were associated with novel ultrasonographic findings. Conclusions Based on specific ultrasonographic phenotypes, prenatal genetic testing could be considered in a tailored fashion. Keywords Low-pass genome sequencing; ultrasonographic anomaly; soft marker; copy number variations; aneuploidy; prenatal diagnosis Tweetable abstract Fetuses with structural anomalies and specific soft markers are recommended for copy number variations analysis

In recent years, genome-based classifications for hematological neoplasms have been proposed successively and proved to be more accurate than histologic classifications. However, some previous studies have reported the racial differences of genetic landscape in persons with hematological neoplasms including myelodysplastic syndromes (MDS), which may cause a genomic classification based on a particular ethnic group does not operate in other races. To determine whether race plays an important role in the genomic-based classification, we validated a newly proposed genomic classification of MDS (J Clin Oncol.2021; JCO2001659), which was based on a large European database, in Chinese patients from our center. Our results showed significant differences between Chinese and European patients including proportion of each group to overall cohort when applying this novel genomic classification. Our data indicate that a genomic classification of hematological neoplasms probably should be revised according to specific genetic features in different races.

The impact of the 2022 International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) needs study. We analysed data from 989 MDS subjects classified using the 2016 World Health Organization (WHO) criteria to determine the impact of the new proposal. Our analyses suggested the ICC criteria of MDS-SF3B1 identifies a more homogenous disease entity than the WHO 2016 criteria of myelodysplastic syndromes with ring sideroblasts (MDS-RS). MDS, not otherwise specified with single lineage dysplasia (MDS, NOS-SLD) patients had a better prognosis than MDS, NOS with multilineage dysplasia (MDS, NOS-MLD) patients. MDS with mutated TP53 and MDS/acute myeloid leukaemia with mutated TP53 patients had the briefest survivals. These data support the ICC of MDS, which allows more accurate diagnoses and risk stratification.

Skeletal dysplasias (SDs) are common birth defects, but they are difficult to diagnose accurately according to only the limited phenotypic information available from ultrasound during the pregnancy. To evaluate the application of whole-exome sequencing and expand the data in the prenatal molecular diagnosis of fetuses with SDs, we collected 55 fetuses with SDs based on ultrasonographic features. Whole-exome sequencing (WES) of the fetuses or parent-fetus trio were subjected to sequential tests and produced a diagnostic yield of 64% (35/55). 65% (11/17) of families with a history of adverse pregnancies were diagnosed, 16 genes were involved and 37 different pathogenic or likely pathogenic variants were identified, including 14 novel variants which were first reported in this study. De novo variants were identified in 21 cases (60%, 21/35) among the fetuses with a genetic diagnosis. The pathogenicity of two novel splice-site variants was confirmed by constructing minigene in vitro. Our results revealed that WES can provide new evidence for the relationship between the genotype and phenotype of fetuses with SDs, as well as broaden the mutation spectrum of detected genes, which is significant for prenatal diagnosis and genetic counselling.

Lost circulation in fractured strata during drilling incurs additional costs and leads to difficulties in promoting drilling safety and efficiency. Plugging-while-drilling is a feasible means to address lost circulation in fractured formations. The particle size distribution (PSD) of plugging particles is determined empirically; therefore, it is often not matched with the fracture sealing requirement. This study investigates the lost circulation mechanism of fractured strata and identifies a calcite particle-based material as the preferred plugging agent. The plugging mechanism and the design of PSD and particle concentration are demonstrated. Based on the concentration, a plugging-while-drilling technique was developed for fractured strata. The results show that calcite particles tend to form the filling layer at the fracture inlet, which cuts off the leakage of the drilling fluid into the fracture, eliminating the drilling fluid pressure applied on the fracture surface. Thus, a stable sealing for the fractured formation is achieved, and the pressure-bearing capacity of the borehole wall is increased. The result also reveals the optimal mixing and concentration models for calcite particles with various diameters. The plugging technique based on calcite particles for fractured formations is applied in a field experiment. The results confirm that the technique can improve the chance of lost circulation prevention and thief-zone plugging in fractured strata and remarkably reduce both the event quantity of lost circulation and the volume of circulation loss. The findings of this research lay a theoretical basis to address lost circulation in fractured formations and, thus, have important practical significance.

We used data from 852 consecutive subjects with myelodysplastic neoplasms (MDS) diagnosed according to the 2016 (revised 4th) World Health Organization (WHO) criteria to evaluate the 2022 (5th) edition WHO classification of MDS. 30 subjects previously classified as MDS with an NPM1 mutation were re-classified as acute myeloid leukaemia (AML). 9 subjects previously classified as MDS-U were re-classified to clonal cytopenia of undetermined significance (CCUS). The remaining 813 subjects were diagnosed as: MDS-5q (N = 11 [1%]), MDS-SF3B1 (N = 70 [9%]), MDS-biTP53 (N = 53 [7%]), MDS-LB (N = 293 [36%]), MDS-h (N = 80 [10%]), MDS-IB1 (N = 161 [20%]), MDS-IB2 (N = 103 [13%]) and MDS-f (N = 42 [5%]) and MDS-biTP53 (N = 53 [7%]). 34 of these subjects came from the 53 (64%) MDS-biTP53 previously diagnosed as MDS-EB. Median survival of subjects classified as MDS using the WHO 2022 criteria was 45 months (95% Confidence Interval [CI], 34, 56 months). Subjects re-classified as MDS-biTP53 and MDS-f had significantly briefer median survivals compared with other MDS sub-types (10 months, [8, 12 months] and 15 months [8, 23 months]). In conclusion, our analyses support the refinements made in the WHO 2022 proposal.

Accurate breast lesion surface localization can guarantee accurate biopsy and local treatment. But there is no guideline to regular equipment and methods for the localization of breast lesions. The conventional non-invasive localization method is marker-based localization. The advantages of this method are simple and efficient. The disadvantages are that markers disappear easily under coupling agents; the positioning length of markers cannot last long on skin; and healthcare associated infection due to many patients using the same marker pen is potentially unavoidable. Breast lesion sticker (called sticker for short) is a new-type localization medical instrument in 2020. Our study aims to explore the clinical value of a new lesion stickers in breast lesion surface localization via comparison of the sticker and marker pen localization methods.This was a prospective cohort study. It was conducted in 67 patients who needed breast lesion surface localization before biopsy. The patients were randomly assigned into 2 groups. One group of patients used marker pen to mark breast lesion surface location by ultrasonography. The other group of patients used stickers. Patients labeled with markers on skin were swabbed agents before marking. Then the markers were checked by ultrasound scan. If the surface positions of breast lesion were not correct, the above procedure was repeated. In the sticker group, the stickers were released synchronously after the lesions were detected by ultrasound scan. Then locations were checked via scanning hole. If the surface positions of breast lesion were not correct, the above procedure was repeated. The accuracy of positioning, the length of positioning time and satisfaction of patients between the 2 groups were compared. The length of positioning time was calculated from the time when ultrasound detected the lesion to the time when the surface position of breast lesion was confirmed. The total score of patients' satisfaction was 5 points according to Service Quality Evaluation of SERVQUAL Scale, including sonographers' service attitude and their technical proficiency, other medical staffs' service attitude and their technical proficiency, hospital service procedures, positioning comfort, and positioning effects.All 67 patients were females, aged 18-66 (39.73±13.10). There were 35 patients in the marker pen group and 32 patients in the sticker group. The time length of group used marker pen to localization was 22-88 (52.20±2.90) s, and the sticker group was 3-15 (9.22±0.58) s in length. The length of positioning time for the stickers was significantly shorter than that of the marker (The new breast lesion positioning stickers have more advantages than the marker pen in localization efficiency. It could reduce the workload of medical workers and increase patients' satisfaction to some extent. The stickers can be used not only in the breast lesions surface localization, but also in the skin location of pleural effusion and ascites, the skin location of surface masses, the skin location of thyroid nodule, and many other clinical marker areas, to further expand the scope of clinical application and value of the stickers.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.

T-cell large granular lymphocyte leukemias (T-LGLL) is a heterogeneous disease with special histology, immune phenotype and genetic abnormalities. The 2017 World Health Organization (WHO) Classific...

Ruxolitinib is a safe and effective therapy of myeloproliferative neoplasm-associated (MPN) myelofibrosis. However, often there are dose reductions and/or therapy interruptions because of therapy-related adverse events (AEs), especially anemia and thrombocytopenia. We previously reported combined therapy with prednisone, thalidomide and danazol (PTD) reversed anemia and thrombocytopenia in people with MPN-associated myelofibrosis. We wondered whether adding PTD to ruxolitinib might mitigate the hematologic AEs and thereby avoid the dose reduction of ruxolitinib and improve the efficacy. To test this hypothesis, we conducted a baseline hemoglobin and platelet concentration assignment prospective observational study in 72 patients comparing 3-month dose adjustment and efficacy of ruxolitinib with (N = 53, the study group) or without (N = 19, the control group) PTD. According to the platelet counts, the median daily ruxolitinib doses in the study group increased from 30 to 40 mg by week 12, whereas in the control group it remained at 30 mg (p = 0.019). In the study group 35 patients had a hemoglobin increase ≥10 g/L compared with no patient receiving ruxolitinib only (p 0.001). Platelet increases100 × 10E+9/L were seen in 56.6% and 5.3% of patients in the two groups, respectively (p 0.001). In patients with anemia and thrombocytopenia, 18 patients in the study group had an anemia response at week 12 and 12 had a platelet increase of ≥50 × 10E+9/L. No patient in the control group achieved either response (p 0.001 and p = 0.078). The study group had a more spleen response than the control group (p = 0.046). Peripheral edema and transaminase elevation were the main nonhematologic AEs of PTD. These AEs can be alleviated by adjusting the danazol dose. In conclusion, adding PTD to ruxolitinib improved ruxolitinib-associated anemia and thrombocytopenia, and resulted in a higher ruxolitinib dose.

The 17q12 microdeletion syndrome is a type of syndrome caused by a deletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome. The main clinical features of the syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. The diverse range of phenotypes associated with 17q12 microdeletion limited clinical recognition and diagnosis. In addition, the phenotypic description of this microdeletion is mainly about postpartum. Due to the rarity of the 17q12 microdeletion itself, studies on the prenatal phenotype of the 17q12 microdeletion are limited. This study aims to analyze the prenatal ultrasound features of 17q12 microdeletion, and to investigate the possibility of genotype-phenotype relationship for providing evidence for genetic counseling in such pregnancies.A total of 3 320 pregnant women and their fetuses were collected for the detection of chromosome copy number variation sequencing (CNV-Seq) due to different ultrasound anomalies in Xiangya Hospital of Central South University. The clinical data of pregnant women and their fetuses who were found to harbor 17q12 microdeletion were reviewed, including maternal age, fetus ultrasound findings, gestational week of the invasive procedure, CNV-Seq results, and the pregnancy outcome. CNV-Seq was tested in the parents to verify whether the abnormality was de novo or inherited. The prenatal ultrasound features and CNV-Seq test results of these 12 fetuses were analyzed and their pregnancy outcomes were followed up.Approximately 0.36% (12/3 320) of fetuses were detected to have 17q12 microdeletion, all characterized as renal abnormalities, accounting for 4.2% (12/288) of all prenatal ultrasound with renal abnormalities, accounting for 48% (12/25) of prenatal ultrasound with renal abnormalities and pathogenic chromosomal abnormalities. The sizes of 17q12 deletion ranged from 1.4 to 1.7 Mb, and all of them included the HNF1B gene. Nine cases were de novo, 2 inherited from the mother, and 1 inherited from father. Among 12 fetuses with 17q12 deletion, 11 cases of prenatal ultrasound suggested bilateral hyperechogenic kidneys and 1 case only showed renal cyst, in which 3 fetuses with enlarged kidneys, 1 with clubfeet, and 1 with subependymal cyst. Pregnancy outcomes were available for 11 of the 12 fetuses. Of them, the parents of 9 fetuses with de novo deletion chose to terminate the pregnancy, and 2 live birth babies inherited from their mother with normal renal function had persistent renal echogenicity enhancement after birth.Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.

GZF1 was recently reported as a genetic factor associated with Larsen syndrome. Two patients presenting hip dislocation, scoliosis and severe myopia, as well as hearing loss and other abnormal features, were found to carry two novel compounds heterozygous variants in GZF1 (c.397400del, p. Leu133fs; and c.1474del, p. Met492fs) through whole-exome sequencing. The mRNA expression level of L133fs-GZF1 did not significantly differ from that of WT-GZF1. However, no HA-conjugated mutant protein was detected by western blotting, which was also confirmed by immunofluorescence staining. In addition, both mRNA transcription and protein expression levels of M492fs-GZF1 were significantly lower than those of wild type, and HA-tagged M492fs-GZF1 was mainly distributed in the cytoplasm of HEK 293 T cells. These results suggested that the two variants could lead to loss of function of GZF1. Our study was the second to report the association between GZF1 variants and Larsen syndrome. We also provided functional evidence for the pathogenicity of GZF1 variants, which expands the mutation spectrum and offers a basis for functional research on the role of GZF1 in the development of Larsen syndrome.

Finish-machined high-volume-fraction SiCp/Al (SiC-particle-reinforced Al matrix) composites tend to have poor surface roughness. To explore the effects of various parameters on the surface roughness of these materials, an orthogonal experiment array L16 (4)4 was designed based on the tool nose radius, cutting depth, feed rate, and cutting speed. Surface roughness values were obtained using a TR200 portable roughness metre during finishing cutting experiments, which were conducted on a Mazak CNC lathe. The Taguchi approach and analysis of variance were used to analyse the significance of the various parameters. A model was developed based on a polynomial regression equation to predict the optimum surface roughness and its corresponding parameters. The confirmation experiments showed that there was good consistency in the optimum surface roughness between the predicted and experimental results.

Post-essential thrombocythemia myelofibrosis (post-ET MF) is a type of Philadelphia chromosome-negative MF. Patients with MF treated with ruxolitinib are immunosuppressed, and therefore more at risk of infection. Several opportunistic infections can occur in the first 6 months of ruxolitinib treatment. However, cases of MF complicated by intra-abdominalWe report the case of a 42-year-old female patient who had resumed ruxolitinib at 20 mg twice daily on 28 February 2020 and was referred for management of JAK2Our case indicates that ruxolitinib is a risk factor for GBS infection in MF patients. Accurate pathogen identification is critical for effective antimicrobial treatment and improved patient outcomes.

Many mature gas reservoirs in China have very low formation pressure, like Yakela, Dalaoba, Kekeya etc. The formation pressure coefficient ranges from 0.6 to 0.9. Conventional well killing fluids easily leak into the formation and damage the well productivity. There are alternative well killing fluids in the industry to kill low-pressure formations, including foamy fluid, oil-based emulsion fluid and well killing fluid with density reducing agent. However, the densities of these alternative well killing fluids are mostly higher than 0.8 g/cm3, and the cost is high if large volume of density reducing agent is used to decrease the density to lower than 0.8 g/cm3. In this paper, a formula of nitrogen foamy well killing fluid is developed and successfully used in sand removal operations in low-pressure gas reservoirs. A series of tests are conducted to select the optimal foaming agent, foam stabilizer and other additives. Sodium dodecyl sulfate is selected as the foaming agent. However, the properties of Sodium dodecyl sulfate are not stable in hard water, so we use dodecyl dimethyl betaine with sodium dodecyl sulfate together to increase the foaming ability in tough water environment like in the desert area. Xanthan gum is selected as a foam stabilizer because it can thicken the fluid phase and reduce the drainage speed. Gelatin is also added into the formula because it can form stable coacervate with xanthan gum. The concentration of each additive is also optimized through lots of tests. Then the properties of the foamy well killing fluid are tested. Its density is between 0.50-0.80 g/cm3 and is adjustable. Under the temperature of 150°C, its plastic viscosity is 51mPa.s; its yield point is 51.5 Pa; the half-life period reaches 3055min. These basic properties meet the requirements of being used as well killing fluid. Salinity tolerance and oil resistance tests are also conducted to see the toughest environment that the fluid can be used in. The results show that the formula can be used in the oilfield where the water salinity is less than 100000 mg/L and the oil content is less than 15%. A model of calculating the equivalent density of the foam is developed. Scenarios of field application and onsite maintenance are also established. If a completion operation or a workover operation lasts for more than 24 hours, the foamy fluid needs to be maintained every day to guarantee its performance in the wellbore. The newly formulated well killing fluid has been used in three wells in Yakela condensate gas filed in Tarim Basin, western China, where the formation pressure coefficient is 0.67 and the formation is strongly water sensitive. A foamy well killing fluid density of 0.72g/cm3 was used (surface density 0.53 g/cm3) for the sand removal operation in well Ya2-2-4. No fluid loss has been observed during the whole operational process. Neither gas seepage nor oil overflow has been observed during well killing. The well has recovered from production after workover and the production rate reaches 90×103m3 natural gas with 12t condensate oil every day. The new formula of foamy well killing fluid not only shows good laboratory properties under 150°C, but also proves to be a good solution to the downhole operations in low-pressure and depleted reservoirs.

BACKGROUND Hypomethylating agents (HMA) are considered the first-line therapy for high-risk myelodysplastic syndromes (MDS). However, as the efficacy and safety of rational dosing regimens are lacking, we evaluated the effectiveness and safety of reduced-dose azacitidine (AZA) vs. decitabine (DAC) in adult MDS patients. MATERIAL AND METHODS This retrospective study was conducted at the Institute of Hematology & Blood Diseases Hospital, for hospitalized MDS patients diagnosed (WHO 2008 classification criteria) from May 2006 to February 2020. These AZA- and DCA-naive patients treated with AZA 100 mg/(m²·day) for 5 days to 7 days or DAC 20 mg/(m²·day) for 3 days to 4 days, or 20 mg/(m²·day) 1 day/week for 3 weeks/month were assessed for treatment responses and adverse events. RESULTS Of the 158 enrolled MDS patients, 120 and 38 patients were administered reduced-dose DAC and AZA, respectively. All the patients received a median of 2 treatment cycles. The overall response rates (ORR) were 50.0% and 73.3% in the AZA and DAC groups, respectively (P=0.007). The percentage of platelet transfusion dependence in the AZA group was lower than the DAC group (P=0.026). The multivariate analysis demonstrated that the DAC treatment was a significant factor for improved responses (OR 2.928; 95% CI 1.267-6.896; P=0.012), and the absolute neutrophil count (ANC) was a predictor of the ORR (OR 0.725; 95% CI 0.558-0.898; P=0.008). Neutropenia (P=0.016) and infection (P=0.032) incidences were higher in the DAC group. CONCLUSIONS The reduced-dose DAC group demonstrated a better response than the AZA group in MDS patients with different prognostic risks. The patients' pre-treatment ANC was a significant factor associated with the ORR.

Objective—To analyze the correlation between copy number variations (CNVs) and prenatal ultrasound abnormalities, characterize the CNVs in diverse prenatal phenotypes, and provide detailed follow-up results for prenatal diagnosis. Method—The results obtained in 1152 fetuses referred for chromosome testing due to different ultrasound anomalies were analyzed. CNV detection was performed by chromosomal microarray analysis (CMA) and copy number variation sequencing (CNV-seq). The postnatal outcomes of the fetuses were followed up.Result—Chromosomal abnormalities were detected in 149 of 1152 pregnancies (12.9%), including 84 (7.3%) macroscopic and 65 (5.6%) submicroscopic anomalies. The highest proportion of chromosomal defects was found in fetuses with hydrops (38.5%), followed by fetuses with multiple abnormalities (32.1%). The most common CNV number variation was 22q11 deletion (0.7%), followed by 17q12 deletion (0.4%) and 15q11.2 deletion (0.4%). Bilateral hyperechogenic kidneys were identified in all fetuses with the 17q12 deletion, and all cases of 15q11.2 deletion were positive only for soft markers. On postnatal follow-up of 362 live births, 2 cases of esophageal atresia and 2 cases of craniosynostosis were found that were not accurately diagnosed by prenatal ultrasound.Conclusion—we identified chromosomal abnormalities in approximately one eight of the pregnancies with abnormal ultrasound findings. More emphasis should be placed on the improvement of prenatal detection of esophageal atresia and craniosynostosis.

Additional file 1: Table S1. Gene list of the 112-gene panel. Table S2. Frequency of autoimmune disorders identified in patients with MDS.