[A multicenter study on respiratory pathogen detection with Mycoplasma pneumoniae pneumonia in children].

Objective: To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods: A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15th and December 20th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results: A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ²=10.62,P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×109 vs. 4.06 (2.91, 5.65)×109/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions: The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

[Clinical, imaging and pathological and molecular characteristics of simple bone cyst].

Objective: To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses. Methods: Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis. Results: There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur (n=4), humerus (n=5) and iliac bone (n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions: EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.

[Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

[Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis].

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

Clinical characteristics, outcomes and risk factors for mortality in hospitalized diabetes and chronic kidney disease patients after COVID-19 infection following widespread vaccination.

BACKGROUND: COVID-19 poses a significant threat to patients with comorbidities, such as diabetes and chronic kidney disease (CKD). China experienced a nationwide COVID-19 endemic from December 2022 to January 2023, which is the first occurrence of such an outbreak following China's widespread administration of COVID-19 vaccinations. METHODS: A total of 338 patients with diabetes and CKD combined with COVID-19 infection between December 7, 2022 and January 31, 2023 were included in this study. The end follow-up date was February 10, 2023. Univariate analysis and multivariate Cox analysis were used to analyze risk factors for death. RESULTS: During the 50-day median follow-up period, 90 patients in the study cohort died, for a mortality rate of 26.63%. The median age of the study cohort was 74 years, with a male predominance of 74%. During hospitalization, 21% of patients had incident AKI, 17% of patients experienced stroke, and 40% of patients experienced respiratory failure. Cox proportional hazard regression showed that older age, a diagnosis of severe or critically severe COVID-19 infection, incident AKI and respiratory failure, higher level of average values of fasting glucose during hospitalization, UA, and total bilirubin were independent risk factors for death in our multivariate model. CONCLUSIONS: These findings highlight the critical importance of identifying and managing comorbid risk factors for COVID-19, especially among the elderly, in order to optimize clinical outcomes, even after COVID-19 vaccination.

Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Effect of Multicomponent Intervention on Functional Decline in Chinese Older Adults: A Multicenter Randomized Clinical Trial.

OBJECTIVES: To confirm whether multicomponent exercise following vivifrail recommendations was an effective method for improving physical ability, cognitive function, gait, balance, and muscle strength in Chinese older adults. METHODS: This was a multicenter and randomized clinical trial conducted in Jiangsu, China, from April 2021 to April 2022. Intervention lasted for 12 weeks and 104 older adults with functional declines were enrolled. All participants were randomly assigned to a control (usual care plus health education) or exercise group (usual care plus health education plus exercise). Primary outcomes were the change score of Short Physical Performance Battery (SPPB) and activities of daily living (ADL). The secondary outcomes included instrumental activities of daily living, Tinetti scores, Frailty score, short-form Mini Nutritional Assessment, Mini-Mental State Examination, Geriatric Depression Scale-15, the 12-item Short Form Survey, 4-meter gait speed test, 6-min walking distance, grip strength, and body composition analysis. RESULTS: Among the participants, the average age was 85 (82, 88) years. After 12 weeks of follow-up, the exercise group showed a significant improvement in SPPB, with a change of 2 points (95% confidence interval [0, 3.5], P<0.001) compared to control. In contrast, SPPB remained stable in the control group. Compared to the control group, ADL improved in the exercise group, as did instrumental activities of daily living, Tinetti, Frailty, Short Form Survey, 4-meter gait speed test, and 6-min walking distance. Although there was no significant difference between groups in body composition analysis after post-intervention, the exercise group still improved in soft lean mass (P=0.002), fat-free mass (P=0.002), skeletal muscle mass index (P<0.001), fat-free mass index (P=0.004), appendicular skeletal muscle mass (P<0.001), and leg muscle mass (P<0.001), while the control group had no significant increase. No difference was observed in adverse events during trial period. CONCLUSIONS: The multicomponent exercise intervention following vivifrail recommendations is an effective method for older adults with functional decline and can reverse the functional decline and improve gait, balance, and muscle strength. Additionally, the 12-week multicomponent exercise method provides guidance for Chinese medical professionals working in the field of geriatrics and is a promising method to improve physical function in the general population.

Biomarkers, signaling pathways, and programmed cell death in acute lung injury and its treatment with Traditional Chinese Medicine: a narrative review.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening, high-mortality lung diseases associated with acute and severe inflammation of the lungs. However, research on diagnostic markers and signaling pathways associated with ALI/ARDS is lacking, and no specific drug therapy is available for ALI/ARDS. Therefore, in this study, biomarkers and signaling pathways associated with ALI/ARDS were summarized to provide a reference for future clinical and research work. A review of Traditional Chinese Medicine for the treatment or prevention of ALI/ARDS is also presented to provide a reference for further development of Traditional Chinese Medicine. In summary, this review will help raise awareness of ALI/ARDS and provide insight into the future exploitation of Traditional Chinese Medicine.

[Curative effects of bi-pedicled deep inferior epigastric perforator flap in repairing large soft tissue defects in the lower limbs].

Objective: To investigate the curative effects of bi-pedicled deep inferior epigastric perforator (DIEP) flap in repairing large soft tissue defects in the lower limbs. Methods: A retrospective observational study was conducted. From February 2016 to June 2020, 16 patients with large soft tissue defects in the lower limbs caused by trauma or after tumor/scar resection were admitted to the Department of Hand Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, including 9 males and 7 females, aged 25-58 years, with the area of soft tissue defects ranging from 14.0 cm×8.0 cm to 32.0 cm×18.0 cm. Using the abdomen as the donor site, the conjoined abdominal wall flap, i.e., the bi-pedicled DIEP flap (with an area ranging from 15.0 cm×9.0 cm to 32.0 cm×20.0 cm) carrying two sets of the trunk of the deep inferior epigastric artery was designed and resected to repair the wound. The donor site wound was sutured directly. The flap survival and wound healing in the donor and recipient areas were observed after operation. The curative effect was evaluated during the follow-up. At the last follow-up, the American Knee Society score and lower extremity functional scale were used to assess the functions of knee joint and lower limb, respectively. Results: The flaps of 15 patients survived after operation; the flap of one patient had partial infection at the edge after operation but healed after debridement and dressing change. The wounds in the donor and recipient areas of 16 patients all healed well. Follow-up of 16-28 months showed that the recipient area had a good shape and pliable texture, and there was no obvious swollen appearance, hyperpigmentation, or abnormal hair growth; the donor site had linear scar only, with no complications such as abdominal hernia or hyperplastic scar; the functions of knee joint and lower limb were well reconstructed, with no recurrence of tumor. At the last follow-up, among the 4 patients with knee joint injury, 3 cases were excellent and 1 case was good in the evaluation of knee joint function; among the 12 patients with lower limb injury, 9 cases were excellent and 3 cases were good in the evaluation of lower limb function. Conclusions: The donor site of bi-pedicled DIEP flap is concealed with abundant tissue and large area for resection, with which can be used to repair large soft tissue defects in the lower limbs, achieving good short-term results of appearance and function restoration.

Source apportionment and ozone formation mechanism of VOCs considering photochemical loss in Guangzhou, China.

Understanding the sources and impact of volatile organic compounds (VOCs) on ozone formation is challenging when the traditional method does not account for their photochemical loss. In this study, online monitoring of 56 VOCs was carried out in summer and autumn during high ozone pollution episodes. The photochemical age method was used to evaluate the atmospheric chemical loss of VOCs and to analyze the effects on characteristics, sources, and ozone formation of VOC components. The initial concentrations during daytime were 5.12 ppbv and 4.49 ppbv higher than the observed concentrations in the summer and autumn, respectively. The positive matrix factorization (PMF) model identified 5 major emission sources. However, the omission of the chemical loss of VOCs led to underestimating the contributions of sources associated with highly reactive VOC components, such as those produced by biogenic emissions and solvent usage. Conversely it resulted in overestimating the contributions from VOC components with lower chemical activity such as liquefied petroleum gas (LPG) usage, vehicle emissions, and gasoline evaporation. Furthermore, the estimation of ozone formation may be underestimated when the atmospheric photochemical loss is not taken into account. The ozone formation potential (OFP) method and propylene-equivalent concentration method both underestimated ozone formation by 53.24 ppbv and 47.25 ppbc, respectively, in the summer, and by 40.34 ppbv and 26.37 ppbc, respectively, in the autumn. The determination of the ozone formation regime based on VOC chemical loss was more acceptable. In the summer, the ozone formation regime changed from the VOC-limited regime to the VOC-NOx transition regime, while in the autumn, the ozone formation regime changed from the strong VOC-limited regime to the weak VOC-limited regime. To obtain more thorough and precise conclusions, further monitoring and analysis studies will be conducted in the near future on a wider variety of VOC species such as oxygenated VOCs (OVOCs).

Nanoscale LiZnN - Luminescent Half-Heusler Quantum Dots.

Colloidal semiconductor quantum dots are a well-established technology, with numerous materials available either commercially or through the vast body of literature. The prevalent materials are cadmium-based and are unlikely to find general acceptance in most applications. While the III-V family of materials is a likely substitute, issues remain about its long-term suitability, and other earth-abundant materials are being explored. In this report, we highlight a nanoscale half-Heusler semiconductor, LiZnN, composed of readily available elements as a potential alternative system to luminescent II-VI and III-V nanoparticle quantum dots.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

A sex- and site-specific relationship between body mass index and osteoarthritis: evidence from observational and genetic analyses.

OBJECTIVE: We primarily aimed to investigate whether there are phenotypic and genetic links underlying body mass index (BMI) and overall osteoarthritis (OA). We then intended to explore whether the relationships differ across sexes and sites. METHOD: We first evaluated the phenotypic association between BMI and overall OA using data from the UK Biobank. We then investigated the genetic relationship leveraging summary statistics of the hitherto largest genome-wide association studies performed for BMI and overall OA. Finally, we repeated all analyses in a sex- (female, male) and site- (knee, hip, spine) specific manner. RESULTS: Observational analysis suggested an increased hazard of diagnosed OA per 5 kg/m2 increment in BMI (hazard ratio = 1.38, 95% confidence interval (CI) = 1.37-1.39). A positive overall genetic correlation was observed for BMI and OA (rg = 0.43, P = 4.72 × 10-133), corroborated by 11 significant local signals. Cross-trait meta-analysis identified 34 pleiotropic loci shared between BMI and OA, of which seven were novel. Transcriptome-wide association study revealed 29 shared gene-tissue pairs, targeting nervous, digestive, and exo/endocrine systems. Mendelian randomization demonstrated a robust BMI-OA causal relationship (odds ratio = 1.47, 95% CI = 1.42-1.52). A similar pattern of effects was observed in sex- and site-specific analyses, with BMI affecting OA comparably in both sexes and most strongly in the knee. CONCLUSION: Our work demonstrates an intrinsic relationship underlying BMI and overall OA, reflected by a pronounced phenotypic association, significant biological pleiotropy, and a putative causal link. Stratified analysis further reveals that the effects are distinct across sites and comparable across sexes.

[Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review].

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×109/L to 3.3×109/L. Magnetic resonance imaging showed thickened skin of both forearms, while T2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×109/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement (n=19), joint dysfunction (n=11), myalgia/muscle weakness (n=9), and peripheral eosinophilia (n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

Insomnia and multiple health outcomes: umbrella review of meta-analyses of prospective cohort studies.

OBJECTIVES: To evaluate existing evidence of prospective cohort studies on associations between insomnia and multiple health outcomes. STUDY DESIGN: An umbrella review of meta-analyses of prospective cohort studies. METHODS: A systematic search was undertaken in Pubmed, Embase, Cochrane, and Web of Science from inception to October 2021 to find meta-analyses of prospective cohort studies investigating the association of insomnia with any health outcome. The summary relative risk (SRR) for each meta-analysis was recalculated with random-effects model. The methodological quality and the quality of evidence were assessed by the A Measurement Tool to Assess Systematic Reviews and Grading of Recommendations, Assessment, Development and Evaluation, respectively. RESULTS: A total of 25 published meta-analyses of prospective cohort studies, reporting 63 SRRs for 29 unique outcomes were included. Insomnia was mainly related to cardiovascular outcomes and mental disorders. The former comprised atrial fibrillation (SRR: 1.30, 95% confidence interval: 1.26 to 1.35), cardiovascular diseases (1.45, 1.29 to 1.64), coronary heart disease (1.28, 1.10 to 1.50), myocardial infarction (1.42, 1.17 to 1.72), and stroke (1.55, 1.39 to 1.72). The latter involved alcohol abuse (1.35, 1.08 to 1.67), all mental disorders (2.16, 1.70 to 3.97), anxiety (3.23, 1.52 to 6.85), depression (2.31, 1.90 to 2.81), suicidal ideation (2.26, 1.79 to 2.86), suicidal attempt (1.99, 1.31 to 3.02), and suicidal death (1.72, 1.42 to 2.08). Besides, insomnia enhanced the risk of Alzheimer's disease (1.51, 1.06 to 2.14) and hyperlipidemia (1.64, 1.53 to 1.76). CONCLUSION: Insomnia exhibits considerable adverse outcomes, primarily comprises cardiovascular outcomes and mental disorders, but further studies with robustly designed trials are needed to draw firmer conclusions.