Genetic parameter estimation and genetic evaluation of important economic traits in white and yellow broilers.

1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

[Clinical features and prognosis of hepatosplenic candidiasis in patients with hematopathy].

Hepatosplenic candidiasis (HSC) is a rare type of candidiasis that can occur in patients with hematologic malignancies, hematopoietic stem cell transplantation. At present, there is still a lack of studies on HSC in patients with hematologic disorders. Based on The Chinese Guidelines for the Diagnosis and Treatment of Invasive Fungal Disease in Patients with Hematological Disorders and Cancers (the 6th revision), We retrospectively analyzed the clinical characteristics and prognosis of patients with HSC treated in Peking University Institute of Hematology from 2008 to 2022. Finally, eighteen patients were included, with 1 (5.6%) proven, 2 (11.1%) probable, and 15 (83.3%) possible HSC. Among them, 3 (16.7%) patients occurred after haploid hematopoietic stem cell transplantation and 15 (83.3%) patients occurred after chemotherapy. 6 (33.3%) patients had positive blood cultures, including 4 cases of Candida tropicalis and 2 cases of Candida albicans. At 4 weeks of antifungal therapy, 10 (58.8%) patients achieved partial response (PR), At 8 weeks, 1 (6.3%) patients achieved complete response and 10 (62.5%) patients achieved PR. At 6 months after diagnosis, 3 (16.7%) patients died of hematopoietic recurrence, and none of them died of HSC. As a rare fungal infection disease, HSC has a low positive rate of microbiological and histological examinations, a persistent treat cycle, and has difficulty in remission, reminding us of the need for vigilance in patients with hematopoietic disorders and persistent fever.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

[Feasibility study on the use of peripheral blood differentially expressed genes for objective classification of chronic subjective tinnitus: a case study on high-frequency tinnitus].

Objective: To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF). Methods: From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score. Results: A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance. Conclusions: Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model's generalizability, cross-dataset performance, and algorithm optimization.

[Construction and validation of clinical prediction model of tongue base collapse under drug-induced sleep endoscopy in OSA patients].

Objective: To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction. Methods: This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language. Results: Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998),P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95%CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95%CI: 0.625-0.876). Conclusions: Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

[Therapeutic efficacy of transoral robotic surgery with the da Vinci robot system for the treatment of oropharyngeal squamous cell carcinoma].

Objective: To evaluate the clinical efficacy of transoral robotic surgery (TORS) with the da Vinci robot system in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Methods: A mixed cohort study was conducted to collect and analyze the clinical data of OPSCC patients who underwent TORS at the Eye & ENT Hospital, Fudan University between July 2020 and February 2023 (TORS group). OPSCC patients who underwent conventional surgery between January 2016 and September 2020 were included as the control group. The baseline information, incidence of complications and follow-up data were compared between the two groups. Results: A total of 166 patients were included, with 102 cases (81 males and 21 females) in the TORS group [mean age: (59.1±9.8) years] and 64 cases (54 males and 10 females) in the control group [ mean age: (57.6±9.7) years]. Compared with the control group, the TORS group had lower postoperative bleeding rate [2.9% (3/102) vs 10.9% (7/64), P=0.035] and infection rate [1.0% (1/102) vs 18.8% (12/64), P<0.001]. No statistically significant differences were observed in tracheotomy rate [46.1% (47/102) vs 59.4% (38/64), P=0.070] and median length of hospital stay [8 (7, 10) d vs 10 (4, 12) d, P=0.088]. After propensity score matching, compared with the control group, the TORS group had lower postoperative infection rate [0 (0/31) vs 19.4% (6/31), P=0.032] and median length of hospital stay [7 (7, 10) d vs 10 (8, 12) d, P=0.031]. No statistically significant differences were found in postoperative bleeding rate [3.2% (1/31) vs 6.5% (2/31), P=1.000] and tracheotomy rate [22.6% (7/31) vs 45.2% (14/31), P=0.060] between the two groups. Moreover, 1-and 2-year disease-free survival rates were 96.3% and 94.6% in the TORS group, and 90.6% and 84.3% in the control group, respectively (P=0.233). The 1-and 2-year cancer-specific survival rates were both 100% in the TORS group, and 96.9% and 93.8% in the control group, respectively (P=0.539). Conclusion: TORS for OPSCC is associated with high clinical safety and favorable oncological outcomes.

[Diagnostic value and influencing factors of endobronchial ultrasound-guided transbronchial needle aspiration combined with Xpert MTB/RIF for intrathoracic lymph node tuberculosis].

Objective: To evaluate the sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) puncture to obtain intrathoracic lymph node samples combined with Xpert MTB/RIF (Xpert) detection for the diagnosis of intrathoracic lymph node tuberculosis. Methods: From March 2018 to June 2021, 106 patients [55 males and 51 females, age (45.1±18.6) years] with suspected intrathoracic lymph node tuberculosis and EBUS-TBNA were collected in Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, including 64 patients with subsequent diagnosis of intrathoracic lymph node tuberculosis and 42 patients without tuberculosis. Xpert test and traditional etiology test were performed on the patients' intrathoracic lymph node puncture specimens. The positive results of different detection methods and different methods were analyzed, and the influencing factors of Xpert independent detection positive were analyzed by univariate and multivariate logistic regression. Results: The sensitivity of Xpert was 65.6% (95%CI: 52.7%-77.1%), the specificity was 97.6% (95%CI: 87.4%-99.9%), the positive predictive value was 97.7% (95%CI: 85.7%-99.7%), the negative predictive value was 65.1% (95%CI: 57.0%-72.4%). The positive rate of Xpert alone (65.6%, 42/64) was not significantly different from that of MGIT960, histopathology and Xpert combined detection (70.3%, 45/64) (P<0.05). Multivariate logistic regression analysis showed that the location of the diseased lymph nodes in the mediastinum (OR=5.84, 95%CI: 1.112-30.704, P=0.037), necrosis in the lymph nodes (OR=6.32, 95%CI: 1.460-27.384, P=0.014), and the axial depth of the lymph nodes≥17 mm (OR=6.61, 95%CI: 1.408-30.969, P=0.017) were the promoting factors for the positive Xpert test. Conclusions: EBUS-TBNA combined with Xpert detection has a high clinical diagnostic value for intrathoracic lymph node tuberculosis. When the number of puncture samples is small, Xpert detection can be preferred. The positive rate of Xpert detection can be improved by selecting lymph nodes with mediastinal lesions, lymph nodes necrosis, and axial lymph nodes depth≥17 mm for puncture.

Parent-child interaction, appetite self-regulation, and BMIz in Chinese preschoolers: a mediation analysis.

OBJECTIVES: Research on parent-child interaction (PCI) and its impact on children's weight status is a thriving study area. However, their potential pathways have not been established. This study investigated the association between PCI and children's body-mass index z score (BMIz) examining the role of appetite self-regulation (ASR) as a mediator. STUDY DESIGN: Mediation analysis. METHODS: We included children from 33 kindergartens in Wuhan with parents' consent, measuring children's height and weight, and calculating BMIz. To assess the PCI quality, we utilized the Brigance Parent-Child Interactions Scale. Additionally, children's ASR was tested by satiety responsiveness (SR) and food responsiveness (FR) using the Children's Eating Behavior Questionnaire. Quantile regression was employed to examine the PCI-BMIz association, while mediation analysis was conducted to explore ASR's mediating effect on the relationship between PCI and BMIz. RESULTS: Of 3973 children (53.88% boys) included in the analysis, the mean BMIz was 0.24 ± 1.13. The results revealed that children with poorer PCI quality have higher BMIz across all selected BMIz percentiles, except for the 5th percentile. Furthermore, these associations were significant across most percentiles, whether for boys or girls. Mediation analysis suggested that these associations were partially mediated by children's ASR (indFR = -0.026, PFR < 0.001; indSR = -0.058, PSR < 0.001), with stronger effects observed among boys. CONCLUSION: The variation in how strongly BMIz was linked to PCI across different percentiles suggests that children with poorer PCI have higher BMIz. The link is partially mediated through children's ASR. It's important to pay attention to the PCI quality in children with higher BMIz levels, especially in boys.

[Effect of preoperative oral ibuprofen on postoperative pain after dental implantation: a randomized controlled trial].

Objective: To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the Numerical rating scale (NRS) at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively. Results: A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] (Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference (Z=-0.78, P=0.439). Conclusions: Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

[Two cases of systemic mastocytosis with RUNX1-RUNX1T1 positive acute myeloid leukemia treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation and literature review].

Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.

Correlation between left atrial appendage morphology based on fractal dimension quantification and its hemodynamic parameters in patients with atrial fibrillation.

AIMS: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. MATERIALS AND METHODS: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. RESULTS: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (ß = -11.755, P=0.001), LAA FV (ß = -17.364, P=0.004), LAA PEV (ß = -18.743, P<0.001), and LAA WMV (ß = -7.740, P=0.001) in multiple linear regression analysis. CONCLUSIONS: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.

[Prevalence of hypertension, blood pressure control and influencing factors in residents aged 35-75 years in Jiangsu Province].

Objective: To understand the prevalence, blood pressure control, and influencing factors of hypertension in residents aged 35-75 years in Jiangsu Province, and provide data support and basis for hypertension prevention and treatment. Methods: A stratified cluster sampling method was adopted to conduct community population surveys in 22 districts and counties in 12 prefectures in Jiangsu from 2021 to 2022. A total of 123 531 permanent residents aged 35-75 years were included in the study. The questionnaire survey collected the information about the demographic characteristics, disease history, lifestyle, and control of hypertension of study subjects. Statistical software SPSS 23.0 was used for χ2 test and multivariate logistic regression analysis, and Joinpoint 4.9.1.0 software was used to evaluate the trend of age change. Results: The standardized prevalence of hypertension in study subjects was 46.60%, the prevalence was higher in men than in women, and in rural residents than in urban residents, and the standardized blood pressure control rate was 11.24%, and it was lower in men than in women and in rural residents than in urban residents. The hypertension prevalence and control rates showed increasing trends with age (both P<0.001). The multivariate analysis results showed that being man, older age, being rural resident, higher frequency of alcohol consumption, marital status of being separated and widowed, overweight and obese, abdominal obesity and stroke, diabetes mellitus and dyslipidaemic diseases histories, and family history of hypertension were risk factors for hypertension, and being man, being rural resident, living north area, higher frequency of alcohol consumption, and obesity were risk factors for blood pressure control. Conclusions: The prevalence of hypertension in residents aged 35-75 years in Jiangsu was high, and the rate of blood pressure control was low. It is suggested to take integrated intervention measures, especially in in rural residents and people with low levels of education to reduce the disease burden of the patients.

[Prospective association study of sleep status and risk of coronary heart disease in adults in Suzhou].

Objective: To investigate the association between sleep status and the risk for coronary heart disease in adults in Suzhou. Methods: Using the baseline and follow up information of 53 269 local residents aged 30-79 years in China Kadoorie Biobank conducted in Wuzhong District, Suzhou, 51 929 subjects were included in this study after excluding those reporting coronary heart disease, stroke and cancer at the baseline survey. A Cox proportional hazards regression model was used to analyze the association of healthy sleep score (0-3 points) and sleep factors (snoring, insomnia, long sleep duration and nap) with the risk for coronary heart disease. Results: The median follow-up time was 11.12 years, and 1 304 individuals were diagnosed with coronary heart disease during the follow-up. After adjusting for potential confounders, occasional snoring (HR=1.20, 95%CI: 1.04-1.38), usual snoring (HR=1.17, 95%CI: 1.02-1.33), insomnia disorder (HR=1.41, 95%CI: 1.12-1.78), daytime dysfunction (HR=1.56, 95%CI: 1.20-2.03) and perennial nap (HR=1.37, 95%CI: 1.19-1.59) were associated with increased risk of coronary heart disease. Compared with those with sleep score of 0 - 1 (low sleep quality), the people with sleep score of 3 had reduced risk of coronary heart disease by 26% (HR=0.74, 95%CI: 0.63-0.87). Stratified analysis showed that the association of healthy sleep score 3 with risk of coronary heart disease was stronger in low physically active individuals (interaction P<0.05). Conclusions: Snoring, insomnia disorders, daytime dysfunction, and perennial napping were all associated with increased risk for coronary heart disease, and keep healthy sleep mode might reduce the risk for coronary heart disease in adults.

[Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines].

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

[Clinical phenotype and genotype analysis of progressive familial intrahepatic cholestasis type 3 caused by novel ABCB4 gene mutation].

Objective: To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. Methods: The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. Results: The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. Conclusions: The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.

Role of oedema and shrinkage patterns for prediction of response to neoadjuvant chemotherapy and survival outcomes in luminal breast cancer.

AIMS: To explore the independent and additional value of oedema and shrinkage patterns for predicting the disease-free survival (DFS) and neoadjuvant chemotherapy (NAC) response in luminal breast cancer (BC). MATERIALS AND METHODS: Patients with luminal BC who underwent NAC were enrolled in this study from 2017 to 2022. Traditional MRI features include BI-RADS-based MRI descriptors, tumor size, and ADC values, while emerging MRI features include oedema and shrinkage patterns, all of which were evaluated before, early, and after NAC. The changes in features during NAC were also evaluated. The value of features was evaluated through univariate, multivariate analyses. RESULTS: A total of 258 patients were enrolled in this study, of which 77 responded to NAC. Diffuse oedema, stable or increased oedema during early NAC were adverse predictors for treatment response, while a greater reduction in tumor size and increase in ADC value were favorable predictors (all P<0.05). Furthermore, 20 of 60 patients who were followed up experienced recurrence. Diffuse oedema, pre-pectoral or subcutaneous oedema, and non-concentric shrinkage patterns after NAC were risk factors for DFS, whereas a greater increase in ADC value was a protective factor. Incorporating oedema and shrinkage patterns into traditional MRI features improved the predictive performance for treatment response (AUC from 0.76-0.78 to 0.80-0.83) and DFS (C-index from 0.67-69 to 0.75-0.80). CONCLUSIONS: Oedema is an unfavorable predictor for treatment response and survival outcomes, while shrinkage patterns contribute more to the prognostic value, both of which could offer supplementary benefits for clinical outcomes in luminal BC.

[Relationship between physical activity and the risk of morbidity of cerebrovascular disease in Sichuan Province: a prospective study].

Objective: To investigate the morbidity of cerebrovascular disease among residents ≥30 years in Pengzhou, Sichuan Province, and analyze the effect of physical activity level on the risk of morbidity of cerebrovascular disease. Methods: From 2004 to 2008, people from Pengzhou, Sichuan Province were randomly selected. All the local people aged 30-79 were asked to receive a questionnaire survey, physical examination, and long-term follow-up to determine the morbidity of cerebrovascular disease. The physical activity level and the morbidity of cerebrovascular disease were described, and Cox proportional hazard regression models were used to evaluate the association of domain-specific physical activity with the risk of morbidity of cerebrovascular disease. Results: In 55 126 participants, there were 5 290 new cases of cerebrovascular disease, with a cumulative incidence of 9.60%. After the adjustment for multiple confounding factors, multivariate Cox proportional hazard regression analysis showed that increased levels of occupational, transportation, and total physical activity reduced the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). The highest group of occupational physical activity level had the lowest risk of cerebrovascular disease, with a hazard ratio (HR) value of 0.81 (95%CI: 0.75-0.88), the highest group of transportation physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.84 (95%CI: 0.78-0.91), the highest group of total physical activity level had the lowest risk of cerebrovascular disease, with an HR value of 0.87 (95%CI: 0.80-0.94), compared with the lowest group of corresponding physical activity. No association was found between the household/leisure-time physical activity level and the risk of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Conclusions: In project areas of Pengzhou, Sichuan Province, increased physical activity has been associated with reduced morbidity of cerebrovascular disease and its subtypes (cerebral hemorrhage, cerebral infarction). Increased levels of physical activity in adults are encouraged for health benefits.

[Prediction model related to 6-year risk of frailty in older adults aged 65 years or above in China].

Objective: To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis. Results: The M(Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions: The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.