[Questionnaire survey of the application of four objective indicators necessary for standardized diagnosis of Sjögren's syndrome].

Objective: To investigate the current status and challenges of carrying out the four objective indicators which are necessary for the Sjögren's syndrome (SS) diagnosis in hospitals all over China. Methods: A questionnaire survey was conducted online by Questionstar from May to July 2023 among rheumatologists nationwide, to investigate whether unstimulated salivary flow (UWSF), Van Bijsterveld score (VBS), Schirmer test and labial gland focus score (FS) are carried out in their hospitals and the challenges that hinder their development. A cohort of patients with established SS was enrolled to verify the importance of the four objective indicators in diagnosing SS. Statistical analyses were performed using the chi-square test. Results: The questionnaire was completed by rheumatologists from 660 hospitals in 225 cities of 32 provinces, autonomous regions and municipalities all over China (one doctor from each hospital completed the questionnaire), of which 548 (83.0%) were tertiary care hospitals. The rate of carrying out the objective indicators in 660 hospitals was low: UWSF (290/660, 43.9%), FS (497/660, 75.3%) and VBS (393/660, 59.5%). The percentage of hospitals who consider it difficult to carry out UWSF, VBS, minor labial gland biopsy and Schirmer test was 92.6%(611/660), 69.4%(458/660), 59.8%(395/660) and 58.6%(387/660), respectively. All four objective indicators mentioned above could be carried out in only 139 (21.1%) hospitals. In 521 hospitals in which less than four objective indicators could be carried out, 23.2% (121/521) of rheumatologists selected clinical experience to diagnose SS. A total of 180 patients with SS diagnosed by perfecting all objective indices and meeting the 2016 the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were included, 173 females (96%), aged (46.6±13.6) years, with the missed diagnosis rate was 17.8% (32/180) assuming their labial FS was unavailable. In 166 patients with established SS who met the classic 2002 AECG criteria, 160 females (96%), aged (47.0±13.6) years, the missed diagnosis rate was 52.4% (87/166) assuming their labial FS was unavailable; or 10.8% (18/166) assuming their UWSF was unavailable. SS diagnosis couldn't be estimated according to 2002 AECG criteria, assuming both labial FS and UWSF were unavailable in 156 (94.0%) patients with positive anti-SSA/Ro; or assuming either labial FS or UWSF was unavailable in 10 (6.0%) patients with negative anti-SSA/Ro. Conclusion: The application rates of four objective indicators necessary for SS diagnosis are low, the rate of carrying out labial gland biopsy should be increased, and the labial FS reports and UWSF test should be standardized.

[Current situation and prospect of diagnosis and therapy of childhood acute leukemia in China].

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

Association between Resting Heart Rate and Machine Learning-Based Brain Age in Middle- and Older-Age.

BACKGROUND: Resting heart rate (RHR), has been related to increased risk of dementia, but the relationship between RHR and brain age is unclear. OBJECTIVE: We aimed to investigate the association of RHR with brain age and brain age gap (BAG, the difference between predicted brain age and chronological age) assessed by multimodal Magnetic Resonance Imaging (MRI) in mid- and old-aged adults. DESIGN: A longitudinal study from the UK Biobank neuroimaging project where participants underwent brain MRI scans 9+ years after baseline. SETTING: A population-based study. PARTICIPANTS: A total of 33,381 individuals (mean age 54.74 ± 7.49 years; 53.44% female). MEASUREMENTS: Baseline RHR was assessed by blood pressure monitor and categorized as <60, 60-69 (reference), 70-79, or ≥80 beats per minute (bpm). Brain age was predicted using LASSO through 1,079 phenotypes in six MRI modalities (including T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI, and resting-state fMRI). Data were analyzed using linear regression models. RESULTS: As a continuous variable, higher RHR was associated with older brain age (ß for per 1-SD increase: 0.331, 95% [95% confidence interval, CI]: 0.265, 0.398) and larger BAG (ß: 0.263, 95% CI: 0.202, 0.324). As a categorical variable, RHR 70-79 bpm and RHR ≥80 bpm were associated with older brain age (ß [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957]) and larger BAG (0.256 [0.105, 0.407] / 0.638 [0.436, 0.839]), but RHR< 60 bpm with younger brain age (-0.324 [-0.500, -0.147]) and smaller BAG (-0.230 [-0.392, -0.067]), compared to the reference group. These associations between elevated RHR and brain age were similar in both middle-aged (<60) and older (≥60) adults, whereas the association of RHR< 60 bpm with younger brain age and larger BAG was only significant among middle-aged adults. In stratification analysis, the association between RHR ≥80 bpm and older brain age was present in people with and without CVDs, while the relation of RHR 70-79 bpm to brain age present only in people with CVD. CONCLUSION: Higher RHR (>80 bpm) is associated with older brain age, even among middle-aged adults, but RHR< 60 bpm is associated with younger brain age. Greater RHR could be an indicator for accelerated brain aging.

[An intelligent model for classifying supraventricular tachycardia mechanisms based on 12-lead wearable electrocardiogram devices].

OBJECTIVE: To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT) using 12-lead wearable electrocardiogram devices. METHODS: A total of 356 samples of 12-lead supraventricular tachycardia (SVT) electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model, and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October, 2021 to March, 2023 were selected as the testing set. The changes in electrocardiogram parameters before and during induced tachycardia were compared. Based on multiscale deep neural network, an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated. The 3-lead electrocardiogram signals from Ⅱ, Ⅲ, and Ⅴ1 were extracted to build new classification models, whose diagnostic efficacy was compared with that of the 12-lead model. RESULTS: Of the 101 patients with SVT in the testing set, 68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study. The pre-trained model achieved a high area under the precision-recall curve (0.9492) and F1 score (0.8195) for identifying AVNRT in the validation set. The total F1 scores of the lead Ⅱ, Ⅲ, Ⅴ1, 3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597, 0.6061, 0.3419, 0.6003 and 0.6136, respectively. Compared with the 12-lead classification model, the lead-Ⅲ model had a net reclassification index improvement of -0.029 (P=0.878) and an integrated discrimination index improvement of -0.005 (P=0.965). CONCLUSION: The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

High deoxynivalenol and ergot alkaloid levels in wheat grain: effects on growth performance, carcass traits, rumen fermentation, and blood parameters of feedlot cattle.

This study was designed to assess the impacts of a mixture of deoxynivalenol (DON) and ergot alkaloids (EAs) on growth performance, rumen function, blood parameters, and carcass traits of feedlot cattle. Forty steers (450 ± 6.0 kg) were stratified by weight and randomly allocated to 1 of 4 treatments; control-low (CON-L), control-high (CON-H) which contained low or high wheat screenings that lacked mycotoxins at the same level as the mycotoxin-low (MYC-L; 5.0 mg/kg DON, 2.1 mg/kg EA), and mycotoxin-high (MYC-H: 10 mg/kg DON, 4.2 mg/kg EA) diets that included wheat screening with mycotoxins. Steers were housed in individual pens for a 112-day finishing trial. Intake was 24.8% lower (P < 0.001) for MYC steers compared to CON steers. As a result, average daily gains of MYC steers were 42.1% lower (P < 0.001) than CON steers. Gain to feed ratio was also lower (P < 0.001) for MYC steers compared to CON steers. Platelets, alanine aminotransferase, globulins, and blood urea nitrogen were lower (P ≤ 0.008), and lymphocytes, glutathione peroxidase activity (GPx), and interleukin-10 (IL-10) were elevated (P ≤ 0.002) in MYC steers compared to CON steers. Hot carcass weights and backfat thickness were reduced (P < 0.001) in MYC steers, resulting in leaner (P < 0.001) carcasses and higher (P < 0.007) meat yield compared to CON steers. Results suggest that a mixture of DON and EAs negatively impacted health, performance, and carcass traits of feedlot steers, with the majority of this response likely attributable to EAs. However, more research is needed to distinguish the relative contribution of each mycotoxin to the specific responses observed.

Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank.

BACKGROUND: Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear. OBJECTIVE: We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age. DESIGN: This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years). SETTING: A population-based study. PARTICIPANTS: A total of 42,301 dementia-free participants aged 40-70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans. MEASUREMENTS: We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance. RESULTS: At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (ß [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties. CONCLUSIONS: Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.

Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

BACKGROUND: Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. METHODS: A two-phase surveillance project was conducted in Beijing, China, involving 37 centres across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. FINDINGS: We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared with the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. CONCLUSIONS: Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

[Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery].

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

[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.

[Progressive necrotizing xanthogranuloma in both eyes: a case report].

A 55-year-old male patient presenting with 6 months of bilateral difficulty in eye opening was referred to the ophthalmology department. Upon examination, multiple yellowish tumor-like plaques and nodules were observed on the eyelids and chest of the patient, accompanied by keratitis and iridocyclitis. Histopathological examination of the skin lesions on the chest revealed dermal xanthomatous granulomas with progressive necrosis. Bone marrow biopsy showed mantle cell lymphoma. Based on the medical history, the diagnosis of progressive necrotizing xanthogranuloma with mantle cell lymphoma was confirmed. After 6 months of treatment with bendamustine combined with rituximab, there was partial alleviation of ocular symptoms in the patient.

[Proactively embracing the challenges of multimorbidity].

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

Study on the construction of nomogram prediction model for prognostic assessment of heart failure patients based on serological markers and echocardiography.

OBJECTIVE: We aimed to construct a nomogram prediction model for prognostic assessment of patients with heart failure (HF) based on serological markers and echocardiography. PATIENTS AND METHODS: A total of 200 HF patients admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to January 2020 were selected as the research objects. According to the New York Heart Association (NYHA) cardiac function classification, they were divided into 3 groups, including 65 cases of grade II, 97 cases of grade III, and 38 cases of grade IV. Three groups of echocardiographic parameters were compared [including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], differences in serum markers brain natriuretic peptide (BNP), soluble growth-stimulating expression gene 2 (sST2) and the Modified Early Warning Score (MEWS). The patients were divided into two groups according to their clinical outcomes during the follow-up period, including 52 cases in the death group and 148 cases in the survival group. The clinical data of the two groups were compared, and multi-factor logistic regression analysis was performed to screen out the independent risk factors affecting the patient's death. A nomogram model of the patient's mortality risk was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the discrimination and accuracy of the nomogram model. RESULTS: As the cardiac function class of elderly chronic heart failure (CHF) patients increases, LVEDD, LVESD, sST2, and MEWS increase and LVEF decreases (p<0.05). Multifactor analysis results showed that LVEF, LVEDD, sST2, and MEWS were independent factors affecting the clinical outcome of patients. The AUCs predicted using LVEF, LVEDD, sST2, and MEWS alone were 0.738, 0.775, 0.717, 0.831, and 0.768, respectively. There is a certain degree of discrimination, and the model has extremely high accuracy. CONCLUSIONS: MEWS, LVEDD, and sST2 increase as the NYHA cardiac function grade of HF patients increases and LVEF decreases, which can reflect the severity of the disease to a certain extent. Additionally, the nomogram model established based on this has a high predictive value for the long-term prognosis of patients and can formulate effective intervention measures for quantitative values.

Spatial omics techniques and data analysis for cancer immunotherapy applications.

In-depth profiling of cancer cells/tissues is expanding our understanding of the genomic, epigenomic, transcriptomic, and proteomic landscape of cancer. However, the complexity of the cancer microenvironment, particularly its immune regulation, has made it difficult to exploit the potential of cancer immunotherapy. High-throughput spatial omics technologies and analysis pipelines have emerged as powerful tools for tackling this challenge. As a result, a potential revolution in cancer diagnosis, prognosis, and treatment is on the horizon. In this review, we discuss the technological advances in spatial profiling of cancer around and beyond the central dogma to harness the full benefits of immunotherapy. We also discuss the promise and challenges of spatial data analysis and interpretation and provide an outlook for the future.

Discovery of New Isotopes

Using the fusion-evaporation reaction ^{106}Cd(^{58}Ni,4n)^{160}Os and the gas-filled recoil separator SHANS, two new isotopes _{76}^{160}Os and _{74}^{156}W have been identified. The α decay of ^{160}Os, measured with an α-particle energy of 7080(26) keV and a half-life of 201_{-37}^{+58} µs, is assigned to originate from the ground state. The daughter nucleus ^{156}W is a ß^{+} emitter with a half-life of 291_{-61}^{+86} ms. The newly measured α-decay data allow us to derive α-decay reduced widths (δ^{2}) for the N=84 isotones up to osmium (Z=76), which are found to decrease with increasing atomic number above Z=68. The reduction of δ^{2} is interpreted as evidence for the strengthening of the N=82 shell closure toward the proton drip line, supported by the increase of the neutron-shell gaps predicted in theoretical models.