Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6％)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2％)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5％)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2％)of the 305 patients were classified as poor prognosis,20(6.6％)were classified as good prognosis group,and 22(7.2％)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.

OBJECTIVE: To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL). METHODS: The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed. RESULTS: 144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL. CONCLUSION Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.
Adult ; Humans ; Lymphoma, Mantle-Cell/genetics* ; Bone Marrow/pathology* ; Leukemia/pathology* ; Mutation ; Immunophenotyping

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Objective To investigate the effect and mechanism of astragaloside Ⅳ(AS-Ⅳ) activating ROCK/JNK to regulate autophagy in improving isoproterenol (ISO) induced myocardial fibrosis (MF) in mice. Methods The mice were randomly divided into control operation group (Control group), ISO induced myocardial fibrosis group (MF group), AS-Ⅳ treatment group (AS-Ⅳ group) and combination group of astragaloside IV and Y-33075 (ROCK inhibitor) (astragaloside IV+Y-33075 group). After repeated administration for 30 days. The serum levels of LDH, BNP, CTGF in each group were detected. The cardiac function was detected by ultrasound. Myocardial structure and tissue fibrosis degree in each group were detected by Sirius Red and Masson staining. Oxidative stress (ROS) levels in myocardial tissue of each group were detected by DHE staining and the expression of ROCK, JNK, Atg5, Beclin 1, and LC3 Ⅰ/Ⅱ in myocardial tissue were detected by Western blotting. Results Compared with AS-Ⅳ group, the EF value of AS-Ⅳ+Y-33075 group decreased and the degree of myocardial fibrosis increased (P<0.05). The serum level of LDH, BNP, CTGF increased and the level of ROS in myocardial tissue increased while the expression of ROCK, JNK, Atg5, Beclin 1, LC3 Ⅰ/Ⅱ decreased (P<0.05). Y-33075 could block the protective effect of AS-Ⅳ on myocardial injury induced by MF and inhibit the regulation of AS-Ⅳ on ROCK and JNK. Conclusion AS-Ⅳ could attenuate myocardial fibrosis in mice by activating ROCK/JNK signal and promoting autophagy.

Objective: To investigate the epidemiology, clinical characteristics, on-site dust monitoring and individual protection of the patients with artificial stone-related silicosis. Methods: In March 2022, the literature on artificial stone-related silicosis published from January 1965 to February 2022 was searched in China Journal Full-text Database, Wanfang Database, VIP Database, EMbase and PubMed. Chinese and English search terms include "silica dust""silica dust""silicosis""artificial stone""pneumoconiosis", etc. References were included according to inclusion and exclusion criteria, and data were extracted. The epidemiological characteristics, natural course of disease, workplace dust concentration and individual protection level of patients with artificial stone-related silicosis were analyzed by systematic review. Results: A total of 30 literatures were included, including 7 cohort studies, 14 cross-sectional studies, 3 case-control studies and 6 case reports. A total of 1358 patients with artificial stone-related silicosis were diagnosed from 1997 to 2020, with an average age of 41.5 years old and an average dust exposure time of 11.3 years. Among them, 36.2% (282/778) had progressive mass fibrosis or accelerated progressive silicosis at first diagnosis. Chest imaging showed diffuse small nodule shadow, pulmonary fibrosis, and silico-alveolar proteinosis. Pulmonary function showed restricted or mixed ventilation disorder with or without decreased diffusion volume. The disease progressed rapidly, with progressive mass fibrosis, respiratory failure, and even death. Patients engaged in artificial quartz stone processing, with high concentration of silica including ultra-fine particles, most of which were dry operation, lack of on-site ventilation measures and no effective personal protection. Conclusion: The artificial stone processing workers suffer from artificial stone-related silicosis due to dry cutting, lack of on-site dust removal facilities and personal protective measures, and the disease progresses rapidly, leading to poor prognosis.

Objective: To explore the relationship of physical activity and sedentary leisure time with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of physical activity and sedentary leisure time with low muscle mass, grip strength, and muscle quality. Results: A total of 24 245 participants were included in the analysis. The average daily physical activity level was (18.3±13.8) MET-h/d, and the sedentary leisure time was (4.4±1.9) hours. We took the lowest physical activity quartile as the reference and found that the participants' physical activity was negatively correlated to low muscle mass, strength, and quality. The ORs (95%CIs) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low arm muscle quality (AMQ) were 0.68 (0.60-0.77), 0.66 (0.58-0.75), 0.82 (0.72-0.94) and 0.84 (0.74-0.95), respectively. The subtypes of physical activity, including those related to work, transportation, housework, and leisure, also showed negative correlations with low muscle mass, strength, and quality to varying degrees. Compared with participants with the shortest sedentary leisure time, those who had the longest were more likely to have low TSMI (OR=1.13, 95%CI: 0.99-1.30). Conclusions: Physical activity was negatively correlated with a lower risk of low muscle mass and strength, while longer sedentary leisure time positively correlated with low muscle mass.
Adult ; China ; Exercise ; Humans ; Leisure Activities ; Muscles ; Sedentary Behavior

Objective: To explore the relationship of sleep duration and insomnia with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of sleep duration, insomnia, and its duration with low muscle mass, handgrip strength, and muscle quality. Results: The average sleep duration of the study population was (7.4±1.5) hours. Morbidities of short sleep duration (<6 hours), long sleep duration (≥9 hours), and insomnia were 9.3%,17.4%,and 29.9%,respectively. Compared with those who slept for 7- hours, those who slept for ≥9 hours were more likely to have low muscle mass, low handgrip strength,and low arm muscle quality (AMQ), and the OR (95%CI) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low AMQ were 1.32 (1.18-1.48),1.26 (1.13-1.41), 1.33 (1.18-1.49) and 1.16 (1.03-1.30), respectively. Compared with participants without insomnia, insomnia patients were more likely to have low muscle mass,and the longer the duration of insomnia,the higher the risk (P for trend <0.001). Participants who reported <6 hours sleep duration and insomnia had a higher proportion of low ASMI and low TSMI,compared with those who slept for 7- hours and without insomnia, the OR (95%CI) were 1.26 (1.08-1.47) and 1.25 (1.07-1.46), respectively. Conclusions: Participants who reported ≥9 hours sleep duration were more likely to have low muscle mass,low handgrip strength,and low AMQ. Participants with insomnia had lower muscle mass, and the longer the duration of insomnia, the higher the proportion of low ASMI and low TSMI.
Adult ; China/epidemiology* ; Hand Strength ; Humans ; Muscles ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/epidemiology*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.