Abstract: Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in the activation of B cells and granulocytes, operating downstream of B cell and Fcγ receptors, and is considered an attractive target for treating autoimmune diseases. Preclinical investigations have demonstrated that inhibition of BTK activity holds promise as a potential therapeutic strategy for inflammatory immune responses such as autoimmune diseases and allergies. This review provides an overview of the mechanisms by which BTK contributes to immune-related diseases and summarizes current research on the development of BTK inhibitors for treating these conditions, aiming to offer novel insights into non-oncology applications for BTK inhibitors.

Objective To objectively classify cancer-related fatigue(CRF)patients with qi and blood deficiency syndrome;To explore possible enrichment characteristics;To provide ideas for precise population identification.Methods A cross-sectional study was conducted,611 CRF patients with qi and blood deficiency syndrome were included from October 2019 to April 2022.Clinical symptoms of patient were documented,including pale or withered-yellow complexion,shortness of breath with reluctance to talk,dizziness,spontaneous sweating,and palpitations.Additionally,blood routine were conducted,including white blood cell(WBC)count,red blood cell(RBC)count,hemoglobin(HGB),platelet(PLT)count,and neutrophil count(NEUT).The degree of fatigue was assessed using the Piper Fatigue Scale(PFS).Data analysis was performed using R 4.2.0.Clustering analysis was performed using the K-mediods method.Results Through unsupervised clustering analysis,the target population was divided into three categories:qi and blood deficiency syndrome leaning towards qi deficiency,qi and blood deficiency syndrome with mild symptom,qi and blood deficiency syndrome leaning towards blood deficiency.In terms of fatigue severity,the first two groups showed comparable levels,while the third group exhibited the most severe fatigue.Regarding objective indicators,the group leaning towards qi deficiency had the lowest WBC count,NEUT count and PLT count,and the group leaning towards blood deficiency had the lowest HGB count and RBC count.The group of qi and blood deficiency syndrome with mild symptom exhibited the highest level of objective indicators among the three.Conclusion By using clustering analysis methods,the study has preliminarily achieved population enrichment and classification based on syndromes,providing ideas for subsequent information enrichment and accurate identification of populations.Concurrently,the anemia index,WBC count and NEUT count demonstrate a inclination towards blood deficiency syndrome and qi deficiency syndrome,respectively.These findings indicate that these indicators could be incorporated into the syndrome diagnostic criteria for CRF to aid in the classification of the CRF population.

Humans ; Female ; Mastectomy, Segmental ; Margins of Excision ; Reoperation ; Breast Neoplasms/surgery* ; Retrospective Studies ; Carcinoma, Ductal, Breast/surgery* ; Neoplasm Recurrence, Local

Objective:To investigate the efficacy and safety of precise mechanical thrombectomy based on ABC 2D scale in acute intracranial large artery occlusion stroke (ALVOs). Methods:A prospective study was performed. Two hundred and two patients with ALVOs accepted early mechanical thrombectomy in Department of Neurology, Maoming Clinical School of Guangdong Medical University from January 2021 to February 2022 were enrolled. They were randomly divided into experimental group ( n=102) and control group ( n=100). Stent retriever partially retracted with intermediate catheter for mechanical thrombectomy (SWIM) was the first choice for patients in control group. ABC 2D scale was used to prejudge the pathogenesis of patients in experimental group: patients with scores of 0-3 were considered as having embolic occlusion and a direct aspiration first pass technique (ADAPT) was the first choice, and SWIM would be chosen if suction catheter could not be in place; patients with scores of 4-7 were considered as having intracranial atherosclerotic stenosis occlusion and SWIM was the first choice. The clinical data, surgical effectiveness, surgical safety, and good prognosis rate 90 d after mechanical thrombectomy (modified Rankin scale scores of 0-2 as good prognosis) of the 2 groups were compared. Results:Experimental group had significantly shorter time from puncture to recanalization (51.0[35.0, 78.5] min vs. 67.0[45.0, 100.0] min), and statistically lower NIHSS scores 24 h after mechanical thrombectomy (10.00[4.75, 16.25] vs. 13.00[8.00, 19.00]), significantly higher good prognosis rate 90 d after mechanical thrombectomy (69.6% vs. 46.0%), statistically lower mortality 90 d after mechanical thrombectomy (3.9% vs. 13.0%) compared with control group ( P<0.05). No significant differences were noted in first-pass effect rate, successful vascular revascularization rate, or incidences of symptomatic intracranial hemorrhage (sICH) and ectopic embolization between the control group and experimental group ( P>0.05). Conclusion:Patients with ALVOs accepted early mechanical thrombectomy can have shorter time from puncture to vascular recanalization and better prognosis after etiologically prejudging by ABC 2D scale for thrombectomy.

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Objective:To explore the causes and influencing factors of financial toxicity in young breast cancer survivors, and to provide evidence for intervention program development to improve financial toxicity in young breast cancer survivors.Methods:Using descriptive qualitative research methods, 29 young breast cancer patients from September to December 2021 in Breast Surgery Follow-up Clinic of Fudan University Shanghai Cancer Center were interviewed. The Nvivo 12.0 qualitative data analysis software was used to analyze the data.Results:Four themes were extracted as following, direct cost of cancer treatment was the primary cause of financial toxicity, indirect costs related to cancer and treatment cannot be ignored, long-term effects of cancer and treatment further exacerbated financial toxicity, and cancer-related financial toxicity was also influenced by a variety of other factors.Conclusions:Multiple causes affected the experience of financial toxicity in young breast cancer survivors. The occurrence and risks of financial toxicity in young breast cancer survivors should be assessed. Intervention and support should be provided to meet the needs of young breast cancer survivors.

Objective:To investigate the clinical epidemiological data of children with prolonged mechanical ventilation (PMV) in pediatric intensive care unit(PICU), and analyze the primary disease of children with PMV as well as the disease characteristics and prognosis of children with PMV under different kinds of primary disease.Methods:The clinical data of hospitalized children with PMV in PICU at Children′s Hospital of Fudan University from January 2019 to December 2020 were retrospectively collected.Results:A total of 46 children with PMV were collected.There were 18 males (39.1%) and 28 females (60.9%). The median age was 37 (8, 86) months and the median body weight was 15 (7, 20) kg.The average pediatric critical illness score at admission was 84.2±7.7, PaO 2/FiO 2 was (245.5±99.8)mmHg.The primary diseases leading to PMV were as follows: there were 14 cases of severe pneumonia, eight cases of severe encephalitis, five cases of bronchopulmonary dysplasia, three cases of upper airway obstruction/craniofacial deformity, three cases of myasthenia, three cases of brain stem tumor, three cases of mitochondrial encephalomyopathy, two cases of spinal muscular atrophy, two cases of Prader-Willi syndrome, one case of dermatomyositis, one case of severe brain injury, and one case of central hypoventilation.The causes of unable to withdraw ventilator were respiratory dysfunction in 24 cases, brain dysfunction in 16 cases, and diaphragm dysfunction in six cases.Compared with neuromuscular diseases, children with PMV caused by respiratory diseases had lower month age, higher preterm birth rate, lower PaO 2/FiO 2 ratio, higher parameters for ventilator treatment, and the differences were statistically significant ( P<0.05). Children with PMV caused by neuromuscular diseases had lower Glasgow coma score and higher coma rate, and the differences were statistically significant ( P<0.05). A total of nine (19.6%) cases underwent tracheotomy.A total of 23 (50.0%) cases were successfully extubated from ventilator, six (13.0%) cases were dependent on invasive ventilator, and six (13.0%) cases were breathing with tracheotomy tube.The median mechanical ventilation time was 33 (28, 40) days, the median PICU hospital stay was 42 (34, 56) days, and the median hospital stay was 51 (41, 65) days.A total of 27 (58.7%) cases were improved and discharged, four (8.7%) cases were transferred to rehabilitation hospital, four (8.7%) cases were transferred to local hospital, and 11 (23.9%) cases died in hospital or at home after giving up. Conclusion:The main causes of PMV in PICU children are respiratory dysfunction, brain dysfunction and diaphragm dysfunction.50.0% of the children with PMV could be discharged from the ventilator, and 23.9% died or died after giving up.

Objective:To explore the application effects of mixed courses based on E-disciplinary platform on the teaching of nutrition and food hygiene.Methods:The study included in 31 preventive medicine students from group 1 to 3 Batch 2015 in Binzhou Medical University, who were divided into control group adopting (lecture-based learning, LBL) teaching model. While another 30 students from group 4-6 were divided into the experimental group adopting mixed teaching based on E-disciplinary platform. Analysis and assessments were done by course examinations and questionnaires. SPSS 20.0 was used for t test, rank sum test and chi-square test. Results:According to the course examinations, students in the experimental group got higher scores than those in the control group in terms of usual, examination and overall test scores [(46.17±8.84) points vs. (42.35±8.28) points; (37.31±6.58) points vs. (33.61±6.38) points; (81.97±9.18) points vs. (74.32±8.32) points, ( t=4.69, t=3.16, t=5.16, P< 0.01)]. Furthermore, the experimental group were better than the control group in the number distribution of excellent performance in usual, examination and overall test ( Z=2.71, Z=2.13, Z=4.57, P<0.05). The questionnaires demonstrated that the overall satisfaction rate of the experimental group (77.8%) was higher than that of the control group (47.8%) ( χ2=34.98, P<0.001). Conclusion:Student learning effect and the teaching quality can be improved by applying mixed teaching based on E-disciplinary platform.

Objective:To investigate the clinical practice of chronic kidney disease-mineral and bone disorder (CKD-MBD) in maintenance hemodialysis patients in Shanghai, and to better understand the changes of clinical practice for CKD-MBD.Methods:Sixty-four hospitals with qualified dialysis center in Shanghai were selected for questionnaire survey as of March 2019. The survey questionnaire included the number of hemodialysis and peritoneal dialysis patients, the implementation of CKD-MBD guidelines, the learning of CKD-MBD guidelines, the detection and distribution of CKD-MBD biochemical indicators, the treatment of hyperphosphatemia, the treatment of secondary heperparathyroidism (SHPT) and renal bone disease, and the concentration of calcium ion in dialysate. The results were compared with previous survey data in 2011.Results:There were sixty-three hospitals included in this study, with 10 168 maintenance hemodialysis patients and 4 610 maintenance peritoneal dialysis patients in Shanghai. 84.1%(53/63) hospitals implemented the guidelines smoothly, which increased by 28.5% compared with the rate (55.6%) of 2011. The successful implementation rates for guidelines in secondary and tertiary hospitals were 83.3%(25/30) and 84.8%(28/33) , which increased by 44.0% and 11.7% respectively (39.3% of secondary hospitals and 73.1% of tertiary hospitals in 2011). All hospitals carried out the detection for serum calcium and phosphorus. The rate for parathyroid hormone (PTH), total alkaline phosphatase (AKP), bone specific alkaline phosphatase (BAP), 25-hydroxy vitamin D[25(OH)D], and other bone metabolism-related biomarkers were 98.4%(62/63), 90.5%(57/63), 19.0%(12/63), 90.5%(57/63) and 42.9%(27/63), respectively; coronary artery CT, lumbar lateral X-ray plain, echocardiography, bone mineral density, and vascular ultrasound were carried out in 68.3%(43/63), 74.6%(47/63), 100.0%(63/63), 68.3%(43/63)and 69.8%(44/63), respectively. Compared with 2011, the proportion of detection for PTH, AKP, BAP, 25(OH)D, coronary artery CT, lumbar lateral film and echocardiography increased by 2.1%, 1.6%, 0.5%, 47.9%, 14.6%, 20.9% and 1.9%, respectively. The proportion of patients with serum phosphorus ranging in 0.80-1.45 mmol/L(KDIGO guideline), serum phosphorus ranging in 0.80-1.78 mmol/L(KDOQI guideline), calcium ranging in 2.10-2.54 mmol/L, and PTH ranging in 150-600 ng/L were 37.0%(3 323/8 969), 50.7%(4 571/9 018), 60.2%(5 568/9 244) and 33.2%(3 018/9 087). Compared with 2011(39.6%, 53.5% and 34.1%), the proportion of patients with ideal serum phosphorus (0.80-1.78 mmol/L) and calcium (2.10-2.54 mmol/L) levels increased by 11.1% and 6.7% respectively, and the proportion with PTH 150-300 ng/L decreased by 0.9%. The proportion of hospitals for using non-calcium phosphate binders (lanthanum carbonate from 1.9% to 87.3% and sevelamer carbonate from 14.8% to 63.5%) and surgical treatment (from 38.9% to 68.3%) for SHPT dramatically increased.Conclusions:Through the availability of medicine increases, and nephrologists gain deeper understanding in management and treatment of CKD-MBD, the detection rate for CKD-MBD indicators and the eligible rate have significantly improved compared with those in 2011. However, the comprehensive management of CKD-MBD in Shanghai still faces great challenges. It is still necessary to further improve eligible rate for serum phosphorus and iPTH, so as to provide more evidences and management strategies for integrated management of end-stage renal disease and prevention of abnormal calcium and phosphorus metabolism in patients.

Objective:To investigate the effectiveness and safety of fully-covered self-expandable metal stent (FCSEMS) with plastic stent over the treatment of post liver transplantation anastomotic biliary stricture (AS).Methods:The clinical data of AS patients after liver transplantation admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2014 to April 2018 was collected for the retrospective study. According to different implanted stents, patients were divided into FCSEMS group and plastic stent group. The general information of the two groups of patients, surgical success rate, postoperative complications, the number of endoscopic retrograde cholangiopancreatography (ERCP), the number of indwelling stents and other indicators were compared and analyzed.Results:A total of 54 patients were enrolled, including 41 males and 13 females, with a median age of 48 (34-65) years. A total of 23 cases were included in the FCSEMS group and 31 cases were included in the plastic stent group. The overall technical success rate of the operation was 98.3% (176/179). In the FCSEMS group, there were 21 patients recovered and 2 patients were relieved; in the plastic stent group, 29 patients were recovered, 1 case was relieved, and 1 case failed. There were no statistically significant differences in the efficacy and complication rate between the two groups (all P>0.05). The median stent indwelling time, ERCP times, and the number of indwelling stents in the FCSEMS group were 5.9 months, 2 times, and 1, respectively, and in the plastic stent group were 9.5 months, 4 times, and 8 respectively. There were statistical differences between the two groups (all P<0.05). Conclusions:FCSEMS for treatment of AS showed less duration of stenting, numbers of stents and endoscopic treatment sessions with the similar efficacy as plastic stents. It’s indicated that it’s necessary to pay attention to the probability of stent migration and pancreatitis.