Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.

Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.

Objective:To analyze the clinical characteristics and neurophysiological features of patients with neuralgic amyotrophy (NA) and explore their neurological function status.Methods:Clinical data and neurophysiological findings of 90 patients diagnosed with NA at Beijing Tsinghua Changgung Hospital from September 2016 to January 2024 were collected and their clinical phenotypes and neurophysiological characteristics were systematically summarized and analyzed.Results:Among the 90 patients, males accounted for 60.0% (54 cases) and females accounted for 40.0% (36 cases). The duration of the disease was 12 (3, 36) months (ranged from 1 week to 5 years). The onset age of the patients was 58 (30, 70) (21-87) years. Unilateral involvement was noted in 94.4% (85/90) of patients, exhibiting a left-to-right ratio of 1∶1.3, while only 5.6% (5/90) had bilateral involvement. The majority of patients demonstrated a monophasic clinical course with a recurrence rate of just 2.2% (2/90). The primary clinical manifestations included upper limb pain in 70.0% (63/90) of patients, which progressed to muscle weakness and atrophy within 1 day to 1 month, whereas 30.0% (27/90) of patients without significant pain symptoms. Lesions predominantly affected the upper trunk of the brachial plexus, which accounted for 64.4% (58/90) of patients. Distal nerve injuries in the upper limb were observed in 14.4% (13/90) of patients, with 6.7% (6/90) demonstrating isolated anterior interosseous nerve involvement and another 6.7% (6/90) exhibiting isolated posterior interosseous nerve involvement; 1 case had concurrent anterior and posterior interosseous nerve damage. Additionally, 1 case presented with bilateral phrenic nerve involvement, and another patient had isolated posterior tibial nerve injury. Electrophysiological evaluations of patients with NA revealed that axonal damage to motor nerve fibers was a hallmark feature of the condition. Among patients undergoing motor nerve conduction studies, 68.8% (55/80) exhibited decreased compound muscle action potential amplitude, and 31.3% (25/80) had prolonged latency. Sensory nerve conduction was normal in 60.0% (48/80) of patients, while abnormalities included prolonged latency in 15.0% (12/80), reduced amplitude in 12.5% (10/80), slowed conduction velocity in 8.8% (7/80), and absent waveforms in 3.8% (3/80) of patients. The rates of abnormal nerve conduction findings in motor nerves were the highest in the suprascapular nerve (70.6%, 36/51), followed by the axillary nerve (58.3%, 35/60), musculocutaneous nerve (50.7%, 35/69), long thoracic nerve (6/17), and both anterior and posterior interosseous nerves (7.5%, 6/80 each). In sensory nerves, abnormalities were predominantly noted in the lateral antebrachial cutaneous nerve (30.0%, 12/40). Needle electromyography demonstrated neurogenic damage, most frequently affecting the infraspinatus muscle (69.2%, 18/26), biceps brachii (68.1%, 49/72), and deltoid muscle (65.3%, 47/72). The positive rate of magnetic resonance neurography (MRN) for NA was 62.1% (41/66), among which 63.4% (26/41) showed localized swelling of the brachial plexus, 51.2% (21/41) exhibited T 2 hyperintensity, and 4.9% (2/41) demonstrated denervated changes in the muscles. The positive rate of ultrasound for NA was 71.1% (59/83), with 91.5% (54/59) showing nerve swelling and 8.5% (5/59) exhibiting hourglass constriction .Conclusions:NA is a peripheral neuropathy characterized by spontaneous pain, limb weakness, and (or) muscle atrophy primarily. Its clinical phenotype predominantly involves damage to the upper trunk of the brachial plexus, which can also manifest as isolated mononeuropathy. Neurophysiological findings most commonly reveal the neurogenic damage to the muscles innervated by the upper trunk of the brachial plexus, mainly characterized by the axonal damage to the motor nerves, and pure motor nerve damage may also be observed. MRN and neuroultrasound can assist in qualitative diagnosis.

Objective To study the effect of miR-143-3p on pyroptosis of HCT-116 cells induced by LPS+ATP.Methods The targeting relationship between miR-143-3 p and TLR2 gene was detected by dual luciferase.The pyroptosis model was established after transfection of miR-143-3p mimic.Cell apoptosis was detected by flow cytometry,and the activity of Caspase-1 and LDH was detected by biochemical method.The levels of IL-1β and IL-18 were detected by ELISA.The mRNA levels of NF-κB,TLR2,NLRP3 and GSDMD were detected by q-PCR.The expression of NLRP3 and ASC was detected by immunofluorescence.The protein expressions of TLR2,GS-DMD,p-NF-κB p65 and cleave Caspase-1 were detected by Western blot.Results Dual luciferase assay showed that miR-143-3p targeted TLR2 expression.The expressions of NF-κB,TLR2,NLRP3,GSDMD mRNA and TLR2,GSDMD,p-NF-κB p65,cleave Caspase-1,ASC,NLRP3 protein in miR-143-3p mimic group and si TLR2 group were lower than those in model group.The activity of Caspase-1 and the content of LDH,IL-1β and IL-18 decreased.Conclusion miR-143-3p regulates pyroptosis of ulcerative colitis cells by targeting TLR2 gene and regulating NF-κB/NLRP3/Caspase-1 signaling pathway.

Objective:To investigate the iodine nutritional status of key populations in iodine adequate areas in Henan Province, and provide a basis for timely adoption of targeted prevention and control measures and scientific formulation of iodine supplementation strategies in iodine adequate areas.Methods:From March to September 2022, a cross-sectional survey was conducted in 60 iodine adequate counties (cities, districts) in 13 provincial-level cities in Henan Province. Administrative villages with a median water iodine level of 40 - 100 μg/L within each county (city, district) were stratified by water iodine value (40 - 49, 50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L). One administrative village was selected from each water iodine layer, and 40 non boarding students aged 8 - 10 years old (age balanced, half male and half female) and 20 pregnant women were selected from each administrative village to collect their household edible salt samples and once random urine sample for test salt iodine and urinary iodine contents; and the thyroid volume of children was measured.Results:A total of 12 203 samples of household edible salt were collected from children aged 8 - 10 years old, with a median salt iodine of 24.5 mg/kg, the iodized salt coverage rate was 85.3% (10 414/12 203), and the qualified iodized salt consumption rate was 77.1% (9 406/12 203). A total of 3 999 samples of household edible salt were collected from pregnant women, with a median salt iodine of 24.0 mg/kg, the iodized salt coverage rate was 84.2% (3 366/3 999), and the qualified iodized salt consumption rate was 74.5% (2 981/3 999). A total of 12 241 urine samples from children aged 8 - 10 years old were collected, with a median urinary iodine of 290.4 μg/L. A total of 4 084 urine samples from pregnant women were collectedd, with a median urinary iodine of 233.0 μg/L. The thyroid volume of 11 971 children was examined, and the rate of goiter was 2.1% (257/11 971). Stratified by water iodine content, the median urinary iodine levels of children in 40 - 59, 60 - 79, and 80 - 100 μg/L water iodine groups were 269.7, 298.0 and 308.0 μg/L, respectively, with a statistically significant difference between the groups ( H = 67.32, P < 0.001). The goiter rates of children were 2.2% (100/4 603), 2.1% (80/3 733), 2.1% (77/3 635), respectively, with no statistically significant difference between the groups (χ 2 = 0.03, P = 0.986). The median urinary iodine levels of pregnant women were 225.4, 243.1, 234.4 μg/L, respectively, with a statistically significant difference between the groups ( H = 10.96, P = 0.004). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is at an excessively suitable level, and pregnant women's iodine nutrition is at an appropriate level. It is recommended to strengthen surveillance on the basis of maintaining current prevention and control measures, and adjust prevention and control measures in a timely manner according to changes in iodine nutrition in the population.

Objective This study summarized the clinical data of IBD patients receiving upadacitinib treatment in our hospital,and provided more Chinese data to better guide the treatment of upadacitinib in Chinese IBD population.Methods Clinical data of 11 patients with IBD who received upadacitinib treatment at Anhui Provincial Hospital from March 1,2023 to September 8,2024 were retrospectively analyzed.Platelet count,ESR,CRP,disease severity score,endoscopic score,and adverse reactions were compared before treatment,at the 4th and 8th week of treatment,and clinical response rate,clinical response rate,endoscopic response rate,and endoscopic response rate were calculated.SPSS 25.0 software was used for statistical analysis.Results The platelets,ESR and CRP of patients at the 4th and 8th week after upadacitinib treatment were decreased compared with those before treatment,with statistical significance.At the 4th week,the clinical response rate was 72.72％(8/11),the clinical remission rate was 0,the clinical response rate of UC patients was 83.33％(5/6),and the clinical response rate of CD patients was 60％(3/5).At the 8th week of treatment,the clinical response rate was 100％(10/10),the clinical remission rate was 80.00％(8/10),the clinical response rate of UC patients was 100％(6/6),the clinical remission rate of UC patients was 83.33％(5/6),the clinical response rate of CD patients was 100％(4/4),and the clinical remission rate of CD was 75％(3/4).There were no adverse reactions during treatment.Three patients were re-examined by colonoscopy,all of whom were severe UC patients and achieved mucosal healing.Conclusion Upadacitinib can rapidly,effectively and sustainably control the disease in patients with moderate and severe IBD,with high safety.

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.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

OBJECTIVE: To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD). METHODS: With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer. RESULTS: Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers. CONCLUSION The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
Humans ; Fetus ; Chloroform ; Computational Biology ; Ethnicity ; Ribs

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses’ colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman’s correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.