Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

ObjectiveTo explore the 28-day mortality risk of Klebsiella pneumoniae (KP) bloodstream infections (BSI) and its related influencing factors, thereby providing a scientific basis for the effective control of KP-BSI and improvement of patient prognosis. MethodsFrom January 2018 to December 2024, a retrospective review was conducted on hospitalized patients aged >18 years old treated for KP-BSI at a tertiary hospital in Hangzhou. Logistic and Cox regression analyses were performed to identify the epidemiological characteristics and the risk factors for the 28-day mortality associated with KP-BSI. ResultsA total of 123 patients with KP-BSI were included in this study, comprising 64 cases infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) and 59 cases infected with carbapenem-susceptible Klebsiella pneumoniae (CSKP). Compared with CSKP-BSI, patients with CRKP-BSI more frequently presented with chronic pulmonary disease (χ²=4.29, P=0.038), concomitant infections at other sites (χ²=10.90, P=0.001), and a higher frequency of invasive procedures prior to infection (central venous catheterization, mechanical ventilation, and indwelling urinary catheter), as well as glucocorticoid use, hemodialysis, and blood transfusion (all P<0.05). The 28-day mortality was significantly higher in BSI cases caused by CRKP compared to that caused by CSKP (37.50% vs 5.08%, P<0.001). Cox regression analyses revealed that carbapenem resistance (HR=6.67, 95%CI: 1.48‒30.08, P=0.014) and blood transfusion (HR=3.58, 95%CI: 1.15‒11.19, P=0.028) were risk factors for the 28-day mortality in KP-BSI, while removal of central venous catheters after infection (HR=0.24, 95%CI: 0.08‒0.67, P=0.006) was associated with a reduced risk for the 28-day mortality. ConclusionCarbapenem resistance is associated with mortality outcomes in patients with KP-BSI. Strengthening infection control measures targeting the identified risk factors for CRKP-BSI may improve patient prognosis.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

OBJECTIVE: To analyze a Chinese pedigree affected with Non-syndromic autosomal recessive deafness type 12 (NFNB12), validate the function of candidate variants, and explore the underlying mechanisms. METHODS: A NFNB12 pedigree presented at Henan Provincial People's Hospital in February 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing of the pedigree members. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of mRNA transcription in the peripheral blood samples from the pedigree members, and protein expression was evaluated with Western blotting assay. This study was approved by Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS: WES analysis revealed that the proband has harbored homozygous c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene, for which both parents were identified as heterozygous carriers. RT-PCR analysis demonstrated the sole presence of the variant mRNA in the proband, and both the variant and wild-type mRNAs in both parents. Furthermore, Western blotting analysis indicated that the proband had exclusively expressed the truncated CDH23 protein, while both the normal and truncated forms of the protein were noted in her parents. CONCLUSION The c.6688delG (p.Ala2230Profs*4) variant of the CDH23 gene probably underlay the pathogenesis of NFNB12 in this pedigree. The loss of function of the CDH23 gene resulting from this variant is not related with nonsense-mediated mRNA decay, but rather production of a truncated protein. Above finding has not only enriched the mutational spectrum of the CDH23 gene and offered a method for investigating the function of its variants using peripheral blood samples, but also delineated the molecular basis for the loss of function, which has provided crucial evidence for genetic counseling and prenatal diagnosis for this family.
Humans ; Pedigree ; Male ; Female ; Asian People/genetics* ; Cadherins/genetics* ; Exome Sequencing ; Deafness/genetics* ; Mutation ; China ; Adult ; Cadherin Related Proteins ; Hearing Loss, Sensorineural/genetics* ; East Asian People

Objective:To construct a risk evaluation system for safe operation of medical equipment of the department of pediatric internal medicine on the basis of comprehensive weight,so as to reduce the risk of operating equipment.Methods:The risk evaluation model of managing medical equipment was constructed by using Delphi method,and the evaluation indicators were weighted by analytic hierarchy process(AHP)and entropy weight method,and then,the safety management for equipment was conducted after the relative weights of indicators at each level were determined.A total of 100 used medical equipment in the department of pediatric internal medicine of Yuncheng Central Hospital of Shanxi Province from January 2022 to December 2023 were selected,and they were managed respectively by conventional management mode(50 equipment)and the management mode with risk evaluation system for safe operation of medical equipment(50 equipment).The quality of equipment operation,safety of clinical use and risk control rate of equipment alarm between the two management modes were compared,as well as the recognition scores of the engineers of equipment,doctors,paramedics and managers of relative department,who used and managed equipment,for the two management modes.Results:The average values of maintenance implementation rate,quality inspection qualification rate,disinfection qualification rate and effective response rate of problems of equipment of using the management mode with risk evaluation system were respectively(93.65±3.65)%,(91.45±3.25)%,(93.14±3.69)%and(94.26±3.14)%,which were all higher than these of conventional management mode,and the differences were statistically significant(t=18.599,12.376,11.746,16.006,P＜0.05).The ratios of device-associated infection,stress injury and body fluid extravasation of risk events were respectively 4%(2/50),6%(3/50)and 6%(3/50),which were lower than those of conventional management mode,and the differences were statistically significant(x2=10.714,8.576,9.756,P＜0.05).The recognition scores of the engineers of equipment,doctors,paramedics and managers of relative department for the equipment management of adopting the management mode with risk evaluation system were respectively(92.14±4.01),(93.54±4.63),(93.65±3.36)and(91.57±3.98)points,which were all higher than these of adopting conventional management mode,and the differences were statistically significant(t=15.798,13.331,15.545,13.940,P＜0.05).The average value of qualified rate of threshold value of equipment alarm,and that of operation and maintenance of equipment of adopting the management mode with risk evaluation system were respectively(98.25±3.54)%and(97.36±4.65)%,which were higher than those of the conventional management mode,and the average value of alarm silence rate of the management mode with risk evaluation system was(2.36±1.54)%,which was lower than that of conventional management mode,and the differences were statistically significant(t=11.207,8.813,10.717,P＜0.05).Conclusion:The application of the risk evaluation system for safe operation of medical equipment of the department of pediatrics on the basis of comprehensive weight in the management for equipment can enhance the safety of operating equipment,and reduce the risk of using equipment,and improve the quality of managing equipment.

Objective To examine the phenotypic characteristics of Ecto-5'-nucleotidase(NtSe/CD73)gene knockout mice in restenosis of blood vessels after vein transplantation so as to identify potential targets for early diagnosis and drug treatment of vascular restenosis after clinical coronary artery bypass surgery.Methods CD73 gene knockout mice aged 8-10 weeks were used as the experimental group,and the littermate wild-type mice were used as the control group.Using the inferior vena cava of mice as a donor,we transplanted to the right carotid artery of allogeneic mice with a trocar method to establish a mouse inferior vena cava carotid artery vascular transplantation model.At the 4th week post-model establishment,we systematically evaluated the patency of the transplanted blood vessels,the formation of the vascular intima,the proliferation of the media,the morphology of the elastin layer,and the expression of inflammatory factors.The vascular smooth muscle cells(VSMCs)from the inferior vena cava of mice were isolated in vitro,and the migration and proliferation were assessed with CD73 inhibitor adenosine 5'-(alpha,beta-methylene)diphosphate(APCP).Results In CD73 knockout mice,neointima formation was impaired,the elastic fiber layer was disrupted and lost,and medial smooth muscle cells proliferated more actively.These changes ultimately led to decreased vascular wall elasticity and increased blood flow resistance.The immunohistochemical staining results suggest that in CD73 gene knockout mice the transplanted vein tissue showed extensive infiltration of Mac-2 positive macrophages,and the expression of cytokines interleukin-1 β(IL-1 β),IL-6,and transforming growth factor β(TGF-β)was significantly increased.CD73 deficiency exacerbated inflammatory responses and vascular remodeling in venous tissues.Scratch wound healing and cell proliferation assays revealed that CD73 inhibition promoted VSMCs proliferation,yet concurrently impaired their migratory capacity.Conclusion Knockout of the CD73 gene exacerbates vascular remodeling and inflammatory response in vein grafts,offering crucial insights for the precise diagnosis and targeted treatment of patients with CD73 gene defects undergoing coronary artery bypass surgery in clinical practice.

Purpose To evaluate the diagnostic value of an abbreviated protocol MRI(AP-MRI)based on first post-contrast subtracted(FAST)images for breast cancer detection.Materials and Methods This study included imaging data from 160 female patients with solid breast lesions who underwent breast MRI in the First Affiliated Hospital of Henan University of Chinese Medicine from April 2021 to January 2024.Two AP-MRI protocols were extracted from the full diagnostic protocol(FDP),including:dynamic contrast-enhanced MRI(DCE-MRI)A protocol:FAST and maximum-intensity projection(MIP)images,and DCE-MRI B protocol:FAST+MIP+diffusion-weighted imaging(DWI).Lesions categorized as breast imaging reporting and data system(BI-RADS)1-3 were classified as negative,and those categorized as BI-RADS 4-5 were classified as positive.Pathological findings served as the diagnostic gold standard.Two radiologists independently evaluated the lesions as negative/positive and compared with the gold standard.The sensitivity,specificity and accuracy of the three protocols were compared.Receiver operating characteristic curves were generated for each protocol,and the area under the curve(AUC)was compared.Results The accuracy of the three protocols showed statistically significant differences(Cochran's Qreader1=6.000,P=0.050;Cochran's Qreader2=10.909,P=0.012).The accuracy of the DCE-MRI A protocol was significantly lower than that of the FDP protocol(Z=2.449,Preader1=0.043;Z=2.858,Preader2=0.013).There were no statistically significant differences in sensitivity(Cochran's Qreader1=3.000,P=0.223;Cochran's Qreader2=2.667,P=0.264)or specificity(Cochran's Qreader1=3.000,P=0.223;Cochran's Qreader2=2.800,P=0.247)between the two AP-MRI protocols and the FDP protocol.There were no statistically significant differences in AUC between the DCE-MRI B protocol and the FDP protocol(Z=1.390-1.719,all P>0.05),while the AUC of the DCE-MRI A protocol had lower AUCs than the FDP protocol(Z=1.980,2.441;both P<0.05).Conclusion The AP-MRI protocol combining FAST,MIP and DWI shows diagnostic accuracy comparable to that of the FDP and greatly saves time and cost,suggesting its potential as an alternative imaging strategy for women with dense breasts and as a new diagnostic approach for high-risk populations.

Objective:To investigate the utilization of inpatient service and influencing factors among pneumoconiosis patients in Chongqing within one year, and to provide a reference basis for the formulation of relevant policies by health management departments.Methods:From October 2020 to October 2023, a multi-stage cluster random sampling method was adopted to select 2002 patients with confirmed pneumoconiosis as the research subjects. A questionnaire survey was conducted on their basic information, inpatient service utilization within one year, treatment for pneumoconiosis-related symptoms, and choice of medical service institutions. Chi-square test and logistic regression were used for statistical analysis.Results:All 2002 pneumoconiosis patients were male, with 40.16% (804/2002) aged 46-55 years old, and 83.32% (1668/2002) currently residing in rural areas. The monthly income of the patients was 833 (167, 2000) yuan, and 22.03% (441/2002) had no income. 30.97% (620/2002) of the patients spent more than 5001 yuan per year on treatment for pneumoconiosis, and 14.64% (293/2002) had debts of more than 5001 yuan. 42.06% (842/2002) had no work-related injury insurance. 21.68% (434/2002) of the patients self-assessed their health status as very poor or poor. The one-year inpatient rate of the patients was 51.25% (1026/2002), and the total inpatient time within one year was 18 (10, 51) days. The inpatient expenses were 6000 (1000, 16625) yuan. Through univariate analysis, the one-year inpatient rates of pneumoconiosis patients were statistically significantly different among different age groups, current employment status, annual household income levels, types of pneumoconiosis, stages of pneumoconiosis, presence or absence of work-related injury insurance, whether receiving minimum living allowances and social assistance related to pneumoconiosis, and different segments of self-assessed health status ( P<0.05). Patients with stage Ⅲ pneumoconiosis, those who received social assistance and minimum living allowances related to pneumoconiosis had higher one-year inpatient rates ( P<0.05), with OR values of 3.893, 1.859, and 2.589, respectively. Conclusion:The utilization of inpatient service by pneumoconiosis patients is influenced by demographic characteristics, social support, and disease factors. It is necessary to enhance the occupational disease diagnosis and treatment capabilities of primary health institutions, build a multi-level social support network, and ensure that patients can conveniently access medical services.

Objective:To analyze the clinical features and prognosis of patients with acute cerebral infarction with different variation coefficients of red blood cell distribution width.Methods:A total of 1 080 patients with acute cerebral infarction diagnosed and treated in the First Affiliated Hospital of Xinjiang Medical University from July 2021 to May 2023 were retrospectively selected as the study objects. The coefficient of variation of red blood cell distribution width was determined for all patients, among which 361 patients with the coefficient of variation of red blood cell distribution width was 11.91% to 14.89%(normal group), and 719 patients with the coefficient of variation of red blood cell distribution width was 14.90% to 23.76% (abnormal group). The clinical characteristics and prognosis of patients with acute cerebral infarction with different coefficient of variation of red blood cell distribution width were compared. Spearman test and Pearson test were used to analyze the correlation between the variation coefficient of red blood cell distribution width and clinical characteristics and prognosis of patients with acute cerebral infarction.Results:There were no significant differences in the proportion of cardiac embolism, arteriole occlusion, partial anterior circulation infarction, posterior circulation infarction and lacunar infarction between the two groups ( P>0.05). The proportion of large atherosclerosis, total anterior circulation infarction, recurrent infarction and prognosis grade 4, 5 and 6 in the normal group was lower than those in the abnormal group :48.48% (175/361) vs. 55.22% (397/719), 8.31% (30/361) vs. 96/719 (13.35%), 16.90% (61/361) vs. 25.03% (180/719), 11.91% (43/361) vs. 42.84% (308/719), 5.26% (19/361) vs. 11.68% (84/719), 0.83% (3/361) vs. 7.93% (57/719); the proportion of grade 0, 1 and 2 prognosis in the normal group were higher than that in the abnormal group: 13.85% (50/361) vs. 0.42% (3/719), 21.05% (76/361) vs. 4.17% (30/719), 21.88% (79/361) vs. 4.73% (34/719), there were statistical differences ( P<0.05). There were statistically significant differences in the variation coefficient of red cell distribution width in patients with acute cerebral infarction among different disease inducements, infarct parts, incidence times and prognosis grades ( P<0.05). Spearman test showed that the variation coefficient of red blood cell distribution width was positively correlated with the infarct volume in patients with acute cerebral infarction ( r = 0.591, P<0.05). The results of Pearson test showed that the variation coefficient of red blood cell distribution width was not correlated with the cause of disease and the location of infarction in patients with acute cerebral infarction ( P>0.05), but was positively correlated with the frequency of incidence and prognosis grade ( r = 0.079, 0.402, P<0.05). Conclusions:Higher coefficients of variation of erythrocyte distribution width are associated with larger infarct size, higher risk of recurrence, and worse prognosis in acute cerebral infarction.

Objective To evaluate the degree of invasion of placental implantation by quantitative delin-eation of MRI placental bed abnormal hyperplasia vessels by 3D-Slicer software.Methods Fifty-seven pa-tients with placenta implantation requiring MRI in Quanzhou Maternal and Child Health Hospital from July 2020 to December 2023 were retrospectively collected and divided into the penetrating placenta implantation group(n=11)and the non-penetrating placenta implantation group(n=46),and the differences of MRI mor-phological signs between the two groups were analyzed.Among them,37 patients with placental bed xenogenic vessels scanned by MRI were screened and there were 11 cases in the penetrating placental implantation group and 26 cases in the non-penetrating placental implantation group.3D-Slicer software was used to delineate the surface area and volume of placental bed xenogenic vessels,the differences between the two groups were ana-lyzed.Results There were significant differences in the surface area and volume of xenogenic blood vessels in placental bed between the two groups(P＜0.05).The large surface area of xenogenic vessels in the placental bed was an independent risk factor for penetrative placental implantation,and the predicted area under the curve(AUC)of penetrative placental implantation was 0.927.When the surface area of the placental bed was 1 079.25 mm2,the sensitivity was 81.8%and the specificity was 88.5%.Conclusion According to 3D-Slicer soft-ware,the diagnostic efficacy of placental bed allogenic blood vessel surface area for penetrating placental implanta-tion is high.The larger the allogenic blood vessel surface area is,the deeper the placental invasion of uterus is.