[Report of six cases with mast cell leukemia and a literature review].

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia (n=4), fatigue (n=3), fever (n=2), abdominal discomfort (n=2), osteolytic lesions (n=2), dizziness (n=1), skin flushing (n=1), and weight loss (n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) µg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

[Accuracy and efficiency of 2D/3D single-vertebra spine navigation registration method based on dual-view feature fusion].

Objective: To investigate the accuracy and efficiency of spine 2D/3D preoperative CT and intraoperative X-ray registration through a framework for spine 2D/3D single-vertebra navigation registration based on the fusion of dual-position image features. Methods: The preoperative CT and intraoperative anteroposterior (AP) and lateral (LAT) X-ray images of 140 lumbar spine patients who visited Huashan Hospital Affiliated to Fudan University from January 2020 to December 2023 were selected. In order to achieve rapid and high-precision single vertebra registration in clinical orthopedic surgery, a designed transformation parameter feature extraction module combined with a lightweight module of channel and spatial attention (CBAM) was used to accurately extract the local single vertebra image transformation information. Subsequently, the fusion regression module was used to complement the features of the anterior posterior (AP) and lateral (LAT) images to improve the accuracy of the registration parameter regression. Two 1×1 convolutions were used to reduce the parameter calculation amount, improve computational efficiency, and accelerate intraoperative registration time. Finally, the regression module outputed the final transformation parameters. Comparative experiments were conducted using traditional iterative methods (Opt-MI, Opt-NCC, Opt-C2F) and existing deep learning methods convolutional neural network (CNN) as control group. The registration accuracy (mRPD), registration time, and registration success rate were compared among the iterative methods. Results: Through experiments on real CT data, the image-guided registration accuracy of the proposed method was verified. The method achieved a registration accuracy of (0.81±0.41) mm in the mRPD metric, a rotational angle error of 0.57°±0.24°, and a translation error of (0.41±0.21) mm. Through experimental comparisons on mainstream models, the selected DenseNet alignment accuracy was significantly better than ResNet as well as VGG (both P<0.05). Compared to existing deep learning methods [mRPD: (2.97±0.99) mm, rotational angle error: 2.64°±0.54°, translation error: (2.15±0.41) mm, registration time: (0.03±0.05) seconds], the proposed method significantly improved registration accuracy (all P<0.05). The registration success rate reached 97%, with an average single registration time of only (0.04±0.02) seconds. Compared to traditional iterative methods [mRPD: (0.78±0.26) mm, rotational angle error: 0.84°±0.57°, translation error: (1.05±0.28) mm, registration time: (35.5±10.5) seconds], registration efficiency of the proposed method was significantly improved (all P<0.05). The dual-position study also compensated for the limitations in the single-view perspective, and significantly outperforms both the front and side single-view perspectives in terms of positional transformation parameter errors (both P<0.05). Conclusion: Compared to existing methods, the proposed CT and X-ray registration method significantly reduces registration time while maintaining high registration accuracy, achieving efficient and precise single vertebra registration.

Data from multi-scaled measurements for soil, hydraulic, vegetative, and meteorological variables in the Xilin River Basin, Inner Mongolia.

The grazed grasslands of Inner Mongolia offer a critical research setting for studying the impacts of long-term grazing on soil, hydraulic, vegetative, and meteorological variables, and potentially contribute to examine threshold responses to grazing activity or climate dynamics in colder Eurasian temperate grasslands. The dataset consists of long-term observations of soil temperature and moisture, as well as other related parameters across three scales: pedon, field, and catchment scale. This includes: i) At the pedon scale, data collection was conducted on five sites: long-term grazing exclusion since 1979 (UG79), short-term grazing exclusion since 1999 (UG99), continuous grazing (CG), heavy year-round grazing (HG), and moderate winter grazing (WG), from May 2004 to August 2008. Profiled soil moisture at depths of 5, 20, and 40 cm was continuously monitored using theta-probes, while soil temperature at depths of 2, 8, 20, 40, and 100 cm was monitored using Platinum ground temperature probes. Since 2016, newly automated monitoring instruments were also used for continuous monitoring of soil temperature and moisture at depths of 10, 30, 50, 70, and 100 cm at the UG79, UG99, and CG sites. ii) At the field scale, during the growth period from 2004 to 2008, a regular sampling grid (about 100 points) was established in all five sites using differential GPS and UTM systems. Soil water content, water drop penetration time, shear strength, and hydraulic conductivity were measured once per week/month. At the beginning, soil organic carbon concentration, bulk density, soil texture, and plant parameters were also taken at each grid point. iii) At the catchment scale, a field sampling scheme was designed, using land use and soil type as stratification variables. A total of 30 sampling points were selected. At each sampling point, detailed soil surveys were conducted to measure soil profile characteristics, including soil colour, texture, structure, and chemical elements. Additionally, some soil hydrological properties were recorded on site. This dataset offers critical insights into the factors influencing livestock carrying capacity in Mongolian grasslands. The integration of these data types can substantially enhance our understanding and management of these ecosystems.

[Recent evaluation and analysis of the clinical effect of two closed treatment methods in children with intracapsular condyle fracture].

Objective: To summarize and analyze clinical characteristics of pediatric mandibular condylar fractures and the long-term therapeutic effects of closed treatment. Methods: A retrospective study was conducted for pediatric condylar fracture in the Department of Oral and Maxillofacial Surgery of Peking University School and Hospital of Stomatology from October 2015 to October 2019, including 33 males (67.3%) and 16 females (32.7%), with an average age of (8.3±2.1) years old. According to the treatment methods, the children were divided into two groups: group A was a removable occlusal splint accompanied with functional exercise, group B was a pure functional exercise. Forty-nine cases (76 sides) children with intracapsular condylar fracture were included in this study. Twenty-four cases in group A and 25 cases in group B. The maximum month opening increased from (20.0±6.2) mm to (46.0±5.3) mm 6 months after closed treatment. Subjective evaluation, special examination, qualitative analysis and quantitative analysis of imaging were used to evaluate the condylar remodeling and functional recovery of temporom and ibular joint in two groups of children after closed treatment of intracapsular condyle fracture. Results: There was no significant difference in subjective evaluation, maximum opening examination, mouth open-type, mandibular protrusion, lateral movement and qualitative analysis of imaging at the six-month follow-up after injury. Quantitative imaging measurements showed that the condylar anteroposterior diameter and condylar height in Group B were significantly higher than those in Group A after 1 year of injury. Conclusions: Closed treatment for pediatric condylar fractures can achieve satisfactory results. After 6 months of injury, the children in the two groups could recover the temporomandibular joint function and promote the condylar adaptative remodeling.

[Clinical features and prognostic factors of AIDS-associated diffuse large B-cell lymphoma].

To explore the general clinical features and treatment outcomes of patients with AIDS-related diffuse large B-cell lymphoma (AIDS-DLBCL) and provide a theoretical basis for diagnosis and treatment, survival prognosis, prevention and management of AIDS-DLBCL patients. AIDS-DLBCL patients who received combined antiretroviral therapy (cART) at Changsha First Hospital from January 2017 to January 2020 were selected in this study. The survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to analyze the association between AIDS-DLBCL specific variables and progression-free survival and overall survival. Correlation analysis was conducted based on the clinical features of the patients. A total of 50 AIDS-DLBCL patients were included. Their median age (Q1, Q3) was 52 (44, 59) years, of whom 46 (92%) were male. About 20 (40%) patients received treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), while 23 patients (46%) received treatment with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Survival curve analysis showed that the 2-year progression-free survival rate and overall survival rate of AIDS-DLBCL patients were 56.9% and 61.6%, respectively. Patients with RCHOP protocol combined with EBV-DNA≥1 000 copies/ml had higher progression-free survival rate (χ2=3.844, P=0.043) and overall survival rate (χ2=4.662, P=0.031) than those with CHOP protocol combined with EBV-DNA≥1 000 copies/ml. A multivariate analysis showed that male (HR=2.70, 95%CI:1.10-6.80), EB viral load≥1 000 copies/ml (HR=1.75, 95%CI:1.12-2.84), HIV-RNA≥200 copies/ml (HR=4.64, 95%CI: 1.73-12.15), ECOG PS score of 2 to 4 points (HR=3.54, 95%CI:1.62-7.33), and international prognostic index (IPI) score of 3 to 5 points (HR=5.21, 95%CI:1.39-20.14) were at a higher risk of disease progression. Patients with EB viral load≥1 000 copies/ml (HR=0.07, 95%CI:0.05-0.93) on the RCHOP regimen had a small risk of disease progression. Males (HR=2.87, 95%CI:1.65-9.17), EB viral load≥1 000 copies/ml (HR=1.61, 95%CI:4.02-9.36), HIV-RNA≥200 copies/ml (HR=1.19, 95%CI:1.58-2.74), ECOG PS score of 2 to 4 (HR=6.42, 95%CI:2.55-14.33), IPI score of 3 to 5 points (HR=2.78, 95%CI:1.41-12.96) had a high risk of mortality. Patients with EB viral load≥1 000 copies/ml (HR=0.24, 95%CI:0.64-0.90) on the RCHOP regimen had a low risk of mortality. In summary, males, ECOG physical status score of 2 to 4 points, IPI score of 3 to 5 points, EB viral load≥1 000 copies/ml and HIV viral load≥200 copies/ml are risk factors affecting progression-free survival and overall survival of AIDS-DLBCL patients. RCHOP regimen combined with EB viral load≥1 000 copies/ml is a protective factor affecting progression-free survival and overall survival in AIDS-DLBCL patients.

[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Neurocardiology: translational advancements and potential.

In our original white paper published in the The Journal of Physiology in 2016, we set out our knowledge of the structural and functional organization of cardiac autonomic control, how it remodels during disease, and approaches to exploit such knowledge for autonomic regulation therapy. The aim of this update is to build on this original blueprint, highlighting the significant progress which has been made in the field since and major challenges and opportunities that exist with regard to translation. Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding emerges of where and how to target in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), vagus nerve, brainstem, and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical, and molecular) such that closed-loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes.

[Kaixinsan alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex].

OBJECTIVE: To investigate the effect of Kaixinsan (KXS, a traditional Chinese medicine formula) for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism. METHODS: Forty female BALB/c mice were randomized equally into control group, model group, and low- and high-dose KXS treatment groups, and in the latter 3 groups, mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage. Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test, and the changes in serum levels of depression-related factors were examined. RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS. The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control. RESULTS: KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models. RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress, lipid metabolism and iron ion binding in the prefrontal cortex. Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice. In SH-SY5Y cells, both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis. CONCLUSION: KXS alleviates adriamycininduced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

[Analysis of serum IgM antibody and viral nucleic acid test results in measles and rubella cases in China from 2014 to 2023].

Objective: To analyze the results of serum IgM antibody and viral nucleic acid testing in measles and rubella cases in China from 2014 to 2023. Methods: Surveillance data on measles and rubella during 2014-2023 were obtained from the Chinese Disease Prevention and Control Information System, and cases that underwent measles/rubella IgM antibody testing and viral nucleic acid testing were included in the study. Information on the number of cases, vaccination status, and laboratory test results was collected, and laboratory test results were compared among cases with different times of rash or onset and different doses of vaccination. Results: From 2014 to 2023, the total number of measles and rubella surveillance cases was 581 746, and the number of measles and rubella cases that underwent both IgM antibody and viral nucleic acid testing was 39 124 and 21 766, respectively, with a double-positive rate of IgM antibody and viral nucleic acid testing of 63.73% (for measles) and 41.68% (for rubella). The single-positive rate for IgM antibody was 21.12% (for measles) and 27.15% (for rubella). The single-positive rate for viral nucleic acid tests was 13.84% (for measles) and 28.19% (for rubella). According to different days of rash or onset (0-3, 4-5, 6-10 and >10), samples of 24 629 (62.95%) measles cases and 15 785 (72.52%) rubella cases were from within 3 days of rash or onset, and the single positive rate of viral nucleic acid detection was 16.90% (for measles) and 32.07% (for rubella). The single positive rate of IgM antibody increased gradually with the time of onset (measles: χ2trend=314.098, P<0.001, rubella: χ2trend=763.846, P<0.001), and reached 31.66% (for measles) and 53.12% (for rubella) after 10 days of rash or onset. Depending on the number of vaccination doses (1, 2,≥3), the single positive rate of viral nucleic acid detection ranged from 12.93% to 20.29% (for measles) and from 25.30% to 27.88% (for rubella). The single positive rate of IgM antibody detection ranged from 36.89% to 47.47% (for measles) and from 22.81 to 41.15% (for rubella). Conclusions: Combined testing of serum IgM antibody and viral nucleic acids could facilitate laboratory confirmation of measles and rubella cases and was also important for measles and rubella elimination efforts.

[Effects of retinopathy on visual function in type 2 diabetes mellitus].

Objective: To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR. Methods: This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants' near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye's damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level. Results: A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores (ß=0.136, P=0.003), near vision (ß=0.163, P<0.001), visual adaptation (ß=0.092, P=0.042), subjective vision (ß=0.120, P=0.009) and stereo vision (ß=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion: Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

[Disease burden and economic burden of breast cancer in females in China: a synthesis analysis].

Objective: To understand the current and integrated disease burden and economic burden caused by breast cancer in females in China. Methods: Based on six updated data sources, including the series of Chinese Cancer Registry Annual Report, China Death Cause Surveillance Datasets, China Health Statistical Yearbook, GLOBOCAN, Cancer Incidence in Five Continents, Global Burden of Disease Study (GBD), the information about incidence, mortality and disability adjusted life years (DALY) of breast cancer were extracted for the analysis on the current incidence and time trend of breast cancer and predicted disease burden of breast cancer in females in China. Software Joinpoint was used for time trend analysis. The data of economic burden were systematically updated and analyzed by literature review. Results: 1) GLOBOCAN 2022 estimated that the age-standardized incidence rate (ASIR) age-standardized mortality rate (ASMR) and one- year prevalence rate of breast cancer in females were 33.0/100 000, 6.1/100 000 and 40.1/100 000, respectively, in China in 2022. According to Chinese Cancer Registry Annual Report, the ASIR and ASMR were 28.4/100 000 and 5.8/100 000, respectively, in 2018. The China Death Cause Surveillance Datasets showed that the ASMR was 4.5/100 000 in 2021, and the urban to rural area mortality ratio was 1.2∶1. GBD reported that the DALYs of breast cancer were 2.921 million in China in 2021, accounting for 14.4% of the global total. 2) Chinese Cancer Registry Annual Report data showed that the ASIR and ASMR of breast cancer decreased by 2.1% and 11.4%, respectively, in China from 2009 to 2018, while increased by 43.9% and 8.2% in rural area, respectively. The Joinpoint analysis showed that the average annual percentage change (AAPC) of ASIR and ASMR in China were -0.2% (P>0.05) and -1.6% (P<0.05). The AAPC of ASIR and ASMR in rural area were 3.9% (P<0.05) and 0.6% (P>0.05), and -0.3% (P>0.05) and -1.2% (P<0.05) in urban area, respectively. China Health Statistical Yearbook data showed that the urban ASMR decreased by 12.3% from 2014 to 2021 with AAPC of -2.6% (P<0.05). 3) The GLOBOCAN 2022 predicted that, the breast cancer case count and death count in China would be 387 776 and 111 133 by 2050, an increase of 8.6% and 48.2%, respectively, compared with 2022, the increases would be more obvious in people over 65 years old, an increase of 80.8% and 124.9%, respectively. 4) Thirteen individual- based studies reported that the median medical expenditure per patient (M=21 000 to 39 000 Yuan) and length of hospital stay (M=11.0 to 30.5 days) for breast cancer treatment decreased from 2010 to 2019, while the average medical expenditure per visit (M=9 000 to 23 000 Yuan) showed an upward trend. There was only one national-level analysis, which showed that the treatment cost of breast cancer was 25.24 billion Yuan in China in 2018, accounting for 6.4% of the total cancer treatment cost. Conclusions: According to the above updated multi-source data, the incidence and mortality of female breast cancer in China were stable in the past ten years, but the increasing trend in rural area should be noted. The direct medical expenditure of breast cancer treatment per case might decrease, but the population-level economic burden would remain heavy due to population aging.

27-Hydroxycholesterol contributes to hypercholesterolemia-associated aggravation of apical periodontitis in ovariectomized rats and raloxifene counteracts its action.

AIM: The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27-hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model. METHODS: Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C-C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme-linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un-operated rats receiving high-fat/high-cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene. RESULTS: Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro-inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group). CONCLUSIONS: Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action.

Computational analysis and expression profiling of NAC transcription factor family involved in biotic stress response in Manihot esculenta.

The Nascent polypeptide-Associated Complex (NAC) family is among the largest plant-specific TF families and plays an important role in plant growth, development, and stress responses. NAC TFs have been extensively studied in plants such as rice and Arabidopsis; however, their characterization, functions, evolution, and expression patterns in Manihot esculenta (cassava) under environmental stress remain largely unexplored. Here, we used bioinformatic analyses and biotic stress responses to investigate the physicochemical properties, chromosome location, phylogeny, gene structure, expression patterns, and cis-elements in promoter regions of the NAC TFs in cassava. We identified 119 M. esculenta NAC (MeNAC) gene families, unevenly distributed on 16 chromosomes. We investigated expression patterns of all identified MeNAC TFs under Xanthomonas axonopodis pv. manihotis (Xam) infection, strain CHN11, at different time points. Only 20 MeNAC TFs showed expression of significant bacterial resistance. Six MeNACs (MeNAC7, 26, 63, 65, 77, and 113) were selected for functional analysis. qRT-PCR assays revealed that MeNAC7, 26, 63, 65, 77, and 113 were induced in response to XamCHN11 infection and may participate in the molecular interaction of cassava and bacterial blight. Interestingly, MeNAC26, MeNAC63, MeNAC65, and MeNAC113 responded to XamCHN11 infection at 3 h post-inoculation. Furthermore, we identified 13 stress-related cis-elements in promoter regions of the MeNAC genes that are involved in diverse environmental stress responses. Phylogenetic analysis revealed that MeNAC genes with similar structures and motif distributions were grouped. This study provides valuable insights into the evolution, diversity, and characterization of MeNAC TFs. It lays the groundwork for a better understanding of their biological roles and molecular mechanisms in cassava.

[Biological characteristics of triple negative breast cancer with low expression of HER2].

Objective: To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low). Methods: A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups. Results: Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different (P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions: There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

[Treacher Collins Syndrome 2 caused by a novel pathogenic variant in PLOR1D: clinical report and literature review].

Objective: To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2). Methods: Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results: The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband's mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions: Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

[Rituximab based treatment in pediatric Epsstain Bar Virus associated lymphocyte proliferative diseases after aplastic anemia with haplo-identical transplantation:a prospective single centre study].

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased (χ(2)=11.336, P=0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.