[Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma].

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Isotope shifts in electron affinities and in binding energies of Pb and hyperfine structure of 207Pb.

The isotope shifts in electron affinities of Pb were measured by Walter et al. [Phys. Rev. A 106, L010801 (2022)] to be -0.002(4) meV for 207-208Pb and -0.003(4) meV for 206-208Pb by scanning the threshold of the photodetachment channel Pb-(S3/2◦4) - Pb (3P0), while Chen and Ning reported 0.015(25) and -0.050(22) meV for the isotope shifts on the binding energies measured relative to 3P2 using the SEVI method [J. Chem. Phys. 145, 084303 (2016)]. Here we revisited these isotope shifts by using our second-generation SEVI spectrometer and obtained -0.001(15) meV for 207-208Pb and -0.001(14) meV for 206-208Pb, respectively. In order to aid the experiment by theory, we performed the first ab initio theoretical calculations of isotope shifts in electron affinities and binding energies of Pb, as well as the hyperfine structure of 207Pb-, by using the MCDHF and RCI methods. The isotope shifts in electron affinities of 207-208Pb and 206-208Pb are -0.0023(8) and -0.0037(13) meV for the 3P0 channel, respectively, in good agreement with Walter et al.'s measurements. The isotope shifts in binding energies relative to 3P1,2, -0.0015(8) and -0.0026(13) meV for 207-208Pb and 206-208Pb, respectively, are compatible with the present measurements. The hyperfine constant for the ground state of 207Pb- obtained by the present calculations, A(S3/2◦4)=-1118 MHz, differs by a factor of 3 from the previous estimation by Bresteau et al. [J. Phys. B: At., Mol. Opt. Phys. 52, 065001 (2019)]. The reliability is supported by the good agreement between the theoretical and experimental hyperfine parameters of 209Bi.

[A survey on the implementation of cardiovascular surgery for congenital heart disease in China between 2017 and 2021].

Objective: To investigate the inplementation of cardiovascular surgery for congenital heart disease (CHD) in China. Methods: A cross-sectional study was carried out. The CHD cardiovascular surgery data collected by the Chinese Society of Extracorporeal Circulation from 2017 to 2021 in 31 provinces (autonomous regions/municipalities) of China were retrospectively reviewed, the implementation of CHD cardiovascular surgery in different provinces, regions, general/specialized hospitals, and different age groups (whether≤18 years old) were summarized, and the correlation analysis between the number of surgeries carried out in each province/region and the gross regional product and the number of the regional population was performed. Results: Between 2017 and 2021, the annual volume of CHD cardiovascular surgery was 77 120, 77 634, 81 161, 62 663 and 71 492, respectively, showing a decreasing trend. Meanwhile, the proportion of CHD patients aged≤18 years who underwent cardiovascular surgery also showed a downward trend, from 79.8% (61 557/77 120) in 2017 to 58.6% (41 871/71 492) in 2021 (P=0.027). The number of surgical cases varied greatly among different provinces, including 4 provinces with≥5 000 cases and 9 provinces with 2 000-5 000 cases. In the five years, the number of CHD cardiovascular surgeries in Central and East China was the largest, accounting for 41.1%-45.5% of the total surgical cases. The proportion of CHD surgery cases≤18 years old was the highest in Southwest China (69.7%-87.4%) and the lowest in Northeast China (28.2%-68.9%). Except for 2021, the number of cases carried out by each region between 2017 and 2020 was correlated with the gross regional product (r=0.929, 0.929, 0.893 and 0.964, respectively, all P<0.05) and the population (r=0.821, 0.893, 0.821 and 0.857, respectively, all P<0.05). Hospitals that performed more than 100 operations (20.5%±1.2% of the total number of hospitals) completed 86.2%±1.2% of the total number of operations in China during the 5-year period. In 2017 and 2021, the number of CHD cardiovascular surgeries preformed in children's/women's and children's specialized hospitals accounted for 24.3% (18 772/77 120) and 23.8% (17 012/71 492) of the total number of cases in China, respectively. Conclusions: From 2017 to 2021, the number of cardiovascular surgery for CHD decreases slightly, but the proportion of surgery for adult CHD patients increases significantly.There is a strong correlation between the number of CHD operations in each region and their economic development status. The scale of CHD cardiovascular surgery performed in children's hospitals/women's and children's hospitals accounts for about a quarter of the total volume in China.

Ab Initio Uncertainty Quantification of Neutrinoless Double-Beta Decay in

The observation of neutrinoless double-beta (0νßß) decay would offer proof of lepton number violation, demonstrating that neutrinos are Majorana particles, while also helping us understand why there is more matter than antimatter in the Universe. If the decay is driven by the exchange of the three known light neutrinos, a discovery would, in addition, link the observed decay rate to the neutrino mass scale through a theoretical quantity known as the nuclear matrix element (NME). Accurate values of the NMEs for all nuclei considered for use in 0νßß experiments are therefore crucial for designing and interpreting those experiments. Here, we report the first comprehensive ab initio uncertainty quantification of the 0νßß-decay NME, in the key nucleus ^{76}Ge. Our method employs nuclear strong and weak interactions derived within chiral effective field theory and recently developed many-body emulators. Our result, with a conservative treatment of uncertainty, is an NME of 2.60_{-1.36}^{+1.28}, which, together with the best-existing half-life sensitivity and phase-space factor, sets an upper limit for effective neutrino mass of 187_{-62}^{+205} meV. The result is important for designing next-generation germanium detectors aiming to cover the entire inverted hierarchy region of neutrino masses.

Deep Learning-Based Facial and Skeletal Transformations for Surgical Planning.

The increasing application of virtual surgical planning (VSP) in orthognathic surgery implies a critical need for accurate prediction of facial and skeletal shapes. The craniofacial relationship in patients with dentofacial deformities is still not understood, and transformations between facial and skeletal shapes remain a challenging task due to intricate anatomical structures and nonlinear relationships between the facial soft tissue and bones. In this study, a novel bidirectional 3-dimensional (3D) deep learning framework, named P2P-ConvGC, was developed and validated based on a large-scale data set for accurate subject-specific transformations between facial and skeletal shapes. Specifically, the 2-stage point-sampling strategy was used to generate multiple nonoverlapping point subsets to represent high-resolution facial and skeletal shapes. Facial and skeletal point subsets were separately input into the prediction system to predict the corresponding skeletal and facial point subsets via the skeletal prediction subnetwork and facial prediction subnetwork. For quantitative evaluation, the accuracy was calculated with shape errors and landmark errors between the predicted skeleton or face with corresponding ground truths. The shape error was calculated by comparing the predicted point sets with the ground truths, with P2P-ConvGC outperforming existing state-of-the-art algorithms including P2P-Net, P2P-ASNL, and P2P-Conv. The total landmark errors (Euclidean distances of craniomaxillofacial landmarks) of P2P-ConvGC in the upper skull, mandible, and facial soft tissues were 1.964 ± 0.904 mm, 2.398 ± 1.174 mm, and 2.226 ± 0.774 mm, respectively. Furthermore, the clinical feasibility of the bidirectional model was validated using a clinical cohort. The result demonstrated its prediction ability with average surface deviation errors of 0.895 ± 0.175 mm for facial prediction and 0.906 ± 0.082 mm for skeletal prediction. To conclude, our proposed model achieved good performance on the subject-specific prediction of facial and skeletal shapes and showed clinical application potential in postoperative facial prediction and VSP for orthognathic surgery.

[Analysis of clinical effect of arthroscopic release at different time in treating knee adhesion after arthroscopic surgery].

Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.

[A case of hematogenous disseminated tuberculosis in a patient with contradictory reactions treated with thalidomide].

Here we reported a case of a 52-year-old male with a 13-year history of Crohn's disease who developed disseminated tuberculosis after 2 injections of infliximab. The patient was admitted with a chief complaint of fever with headache of 1 month's duration. Mycobacterium tuberculosis DNA was found positive in cerebrospinal fluid and lavage fluid by lumbar puncture and bronchoscopy. He was diagnosed with tuberculous meningitis, pulmonary tuberculosis, tracheobronchial tuberculosis and lymph node tuberculosis. After treatment with anti-tuberculosis and glucocorticoids, the symptoms did not improve, the lesions progressed, and granulomas were formed in the tracheobronchial lumen. These were considered to be contradictory reactions and thalidomide was given together with glucocorticoids. The patient's clinical condition has improved significantly. Treatment was successfully completed after 18 months with 1 HREZLfxLzd/8 HEZCsLzd/1 HEZCs/8 HZCs.

METTL3 Modulates Ctsk+ Lineage Supporting Cranial Osteogenesis via Hedgehog.

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

[Evaluation of the outcomes of cochlear implant in children with auditory neuropathy].

Objective: To investigate the auditory and speech abilities of children with congenital auditory neuropathy (AN) after cochlear implant (CI), and to analyze the role of genetic testing in predicting the postoperative outcomes of CI in AN patients. Methods: Fourteen children diagnosed with AN by audiological battery test and underwent CI surgery in Xijing Hospital of the Air Force Medical University from 2002 to 2021 were included in this study (9 males and 5 females), with an implantation age of (3.1±1.7) years (mean±standard deviation, the same as follows). The preoperative audiological results and deafness gene results were analyzed. Another 52 children with ordinary sensorineural hearing loss (SNHL) were selected as the control group (30 males and 22 females), with an implantation age of (2.2±0.9) years. The demographic factors such as age and gender were matched with those of the AN group. The modified Category Auditory Performance (CAP-Ⅱ) and Speech Intelligence Rate (SIR) were used to evaluate the development of postoperative auditory and speech abilities in two groups. The Mandarin Speech Test System was used to test the speech recognition rate of monosyllabic and disyllabic words and sentences. Matlab 2022 software was used to analyze the data. Results: The results of gene in 14 children with AN showed that 6 cases had OTOF gene mutations, 2 cases (siblings) were confirmed to have TNN gene mutations through whole exome sequencing, and the remaining 6 cases were not find any clear pathogenic gene mutations. All subjects underwent CI surgery with electrodes implanted into the cochlea smoothly, and there were no postoperative complications. After surgery, all AN children had improved auditory and speech abilities, but only 64% (9/14) of AN children with CI had auditory ability scores comparable to the control group of SNHL children (including 2 children with TNN gene mutations), and 36% (5/14) of AN children had lower scores than the control group of SNHL children.The average speech recognition rate of two children with TNN gene mutations was 86.5%, and of two children with OTOF gene mutations was 83.2%. Conclusions: AN children achieved varying degrees of auditory and speech abilities after CI, but the postoperative effects varied greatly. Some children achieved similar results as ordinary SNHL children, but there were still some children whose effects were worse than those of ordinary SNHL children. The postoperative efficacy of CI in two children with AN caused by TNN pathogenic genes were comparable to that of ordinary SNHL in children. Genetic testing had certain reference value for predicting the postoperative effect of CI in AN children.

[Recognition of unilateral auditory neuropathy in children].

Objective: This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN. Methods: A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children's Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software. Results: (1) The UAN group (77.8%) had a significantly higher rate of ABR wave IIIL than the SSD group (20.9%) (P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN (P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ²=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) (Fisher's exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type (P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups (P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ²=6.695, P=0.015). Conclusions: Compared to children with SSD, the occurrence of wave IIIL on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.

Association between health insurance programs and rehabilitation services utilisation among people with disabilities: evidence from China.

OBJECTIVES: Rehabilitation is crucial to improve the health status of people with disabilities. Previous studies mainly analysed the impact of health insurance on utilisation of general health services; the relationship between health insurances and rehabilitation services utilisation among Chinese people with disabilities has been long neglected. This study aimed to analyse the association between health insurance programs and rehabilitation services utilisation among disabled people. STUDY DESIGN: This was a cross-sectional study. METHODS: The data used in this study were derived from 2021 National Household Income Survey of Disabled People and National Basic Database of People with Disabilities conducted by China Disabled Persons' Federation. Logistic regression model was used to analyse the relationship between health insurance and rehabilitation services utilisation, and the propensity score matching method was used to check the robustness of the results. RESULTS: (1) Disabled people insured by the Basic Medical Insurance System for Urban Employees (BMISUE) and the Basic Medical Insurance System for Urban and Rural Residents (BMISURR) were positively associated with rehabilitation service utilisation (odds ratio [OR] = 1.852, 95% confidence interval [CI]:1.268, 2.707; OR = 1.375, 95% CI: 0.962, 1.966). (2) The utilisation level of rehabilitation service among disabled people insured by BMISUE was significantly higher than those insured by BMISURR (OR = 1.355, 95% CI: 1.161, 1.581). (3) The supply of rehabilitation services at the community level was positively correlated with the utilisation by people with disabilities. CONCLUSION: Health insurance can improve the financial accessibility of using rehabilitation services, and the utilisation level will increase as the benefits level of health insurance increase.

[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].

Objective: To investigate the association between cytokines and ocular chronic graft-versus-host disease (cGVHD) and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis, treatment, and evaluation. Methods: A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from the animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology, Xinqiao Hospital, Army Medical University. Results: ① Compared with the control group, mice with cGVHD exhibited elevated serum IL-1ß, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 concentrations (all P<0.05). ② Analysis of the cytokine profiles of the serum and tear samples revealed that compared with patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 [P=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (P=0.030, AUC=0.701) ; elevated IL-8, IFN-γ, CXCL9, and CCL17 in tear samples; and lower IL-10 and CCL19 in tear samples (all P<0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. Conclusions: Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers. Among the identified cytokines in tear samples, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation, offering practical reference value for diagnosis.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

PURPOSE: While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. METHODS: This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. RESULTS: Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10 ng/mL) and moderate (10 to < 20 ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20 ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10 ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. CONCLUSIONS: 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Learning and Memory Impairments With Attention-Deficit/Hyperactivity Disorder.

ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.

[Adolescent female reproductive system dysplasia: a clinical study of 356 cases].

Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.