Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

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.

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

ObjectiveTo screen out the mRNAs involved in the resistance of hepatoma cells to anlotinib using ceRNA microarray. MethodsHigh-dose shock combined with low-dose induction was used to culture hepatoma cells resistant to anlotinib, and CCK8 assay was used to verify the difference in the proliferation of drug-resistant hepatoma cells treated by anlotinib. The ceRNA microarray was used to screen out the differentially expressed genes between drug-resistant hepatoma cells and normal hepatoma cells, and real-time PCR was used to verify the differentially expressed genes detected by some microarrays. the independent samples t-test was used for comparison of continuous data between two groups, and the Kaplan-Meier method was used to analyze the overall survival of hepatoma cells samples, and the log-rank test was used to compare survival rates. Fisher’s exact test was used for chip screening. ResultsThere was a significant difference in gene expression between drug-resistant hepatoma cells and normal hepatoma cells, and 10 genes with the greatest difference were screened out for analysis by reducing the range. There were 4 genes associated with drug resistance and tumor growth, i.e., BIRC2, BIRC7, ABCC2, and MAPK8. There were significant reductions in the expression levels of BIRC2, ABCC2, and MAPK8 (P=0001 4, 0001 2, and 0.011 8), and there was a significant increase in the expression of BIRC7 (P＜0.001). The results of real-time PCR were consistent with those of microarray (t=10.74,32.65,18.34, and 2.80; P=0.000 4, 0.000 1, 0.000 1, and 0.044 8). The high expression of BIRC7 and the low expression of MAPK8 were associated with the significant reduction in survival time (P=0.022 0 and 0.005 6). ConclusionBIRC2, BIRC7, ABCC2, and MAPK8 are differentially expressed between anlotinib-resistant hepatoma cells and normal hepatoma cells and may be involved in the resistance of hepatoma cells to anlotinib.

Objective:To explore the outcome of kidney transplantation from donation after cadaveric death(DCD)with high pathological Remuzzi score.Methods:From January, 2019 to December, 2019, 31 recipients of kidney allograft transplantation from marginal donors with Remuzzi score≥4 in preimplantation biopsy were retrospectively enrolled. They were divided into two groups of dual kidney transplantation(DKT, 14 cases)and single kidney transplantation(SKT, 17 cases). Median Remuzzi score of left kidney(5.05 in DKT group vs 4.92 in SKT group)or right kidney(5.26 vs. 4.58)was comparable. Dual donor kidneys were implanted into ipsilateral iliac fossa. Survival outcomes, kidney function, acute rejection episodes, incidence of delayed graft function(DGF)and proteinuria were recorded within Year 1 post-operation.Results:Proportion of male(92.9% vs. 52.9%, P<0.05)and recipient's body mass index(BMI, 23.93 vs. 21.09)were significant higher in DKT group than those in SKT group. One graft failure occurred in DKT group at Month 11 post-operation. The 1-year graft survival rate was 92.9% in DKT group and 1-year recipient survival rate both 100% in two groups. Mean 12-month serum creatinine[SCr, (164±37.7)μmol/L vs. (154.92±96.2)μmol/L]and estimated glomerular filtration rate[eGFR, (41.84±9.01) vs. (44.8±18.16)ml/(min·1.73m 2)]were comparable between two groups(both P>0.05). There was no occurrence of thrombosis resulting in graft loss. One-year incidence of acute rejection, rate of DGF(42.9% vs 41.2%)and proteinuria(57.1% vs. 41.2%)were comparable between two groups(both P>0.05). Conclusions:Through donor-recipient matching and dual kidney transplant allocation, short-term survival outcome of kidney allograft from marginal donors with high Remuzzi score≥4 is encouraging. However, long-term outcomes should be further examined.

Objective:To summarize the transplant outcomes of pediatric kidney transplantation at a single center and discuss probable measures of improving the outcomes.Methods:A total of 111 pediatric renal transplantation were performed from September 2002 to September 2019. They were divided into adult-donor group ( n=41) and pediatric-donor group ( n=70). Adult-donor group consisted of two subgroups based upon donor sources: living-donor group ( n=19) and deceased-donor group ( n=22). Pediatric-donor group consisted of two subgroups based upon surgical types: single kidney group ( n=48) and en bloc kidney group ( n=22). Clinical data and outcomes of grafts and recipients were retrospectively analyzed. Results:The average age of recipients was (15.6±1.9) years in adult-donor group. None developed delayed graft function (DGF) in living-donor group whereas 6 patients (27.3%) had DGF in deceased-donor group ( P<0.05). During a follow-up period of 22-181 months, 1-year and 5-year graft survivals were 100% vs 94.1% and 93.8% vs 94.1% in living-donor and deceased-donor groups respectively. There were no statistical differences. In pediatric-donor group, the age of donors was significantly lower in en bloc subgroup than that in single kidney subgroup (median: 0.5 vs 6 months, P<0.05). The age of recipients was similar between two subgroups: (9.5±5.3) years in single kidney group vs. 11.5± 1.8 years in en bloc kidney group. In addition, 7 cases of single kidney were transplanted for infant recipients aged under 1 year. Vascular thrombosis occurred in 3 patients (6.3%) of single kidney group, less than that in 5 patients (22.7%) of en bloc kidney group ( P=0.06). During a follow-up period of 4-54 months, 1-year and 2-year graft survivals were 85% and 80% in single kidney group whereas 75% and 70% in en bloc kidney group. However, there was no statistically significant difference. One-year survival was 98% in single kidney group and 95% in en bloc kidney group. Conclusions:For elder pediatric recipients, excellent kidney transplant outcomes may be achieved with grafts from adult donors. For pediatric kidney recipients, transplant outcomes can be further improved with careful assessments and cautious usage of small grafts, particularly those form neonatal donors.

Objective To investigate the effect of quantitative ultrasound bone mineral density test on the screening of osteoporosis in patients with knee osteoarthritis and to explore the relationship between knee osteoar-thritis and osteoporosis. Methods 160 patients with knee osteoarthritis were divided into 4 groups:Ⅰ,Ⅱ,ⅢandⅣby Kellgren-Lawrence and measured height,weight,age,quantitative ultrasound bone mineral density and dual energy X-ray bone density.We compared the T values measured by quantitative ultrasound bone mineral density test and dual energy X-ray bone density,assessed the accuracy of quantitative ultrasound bone mineral density test for osteoporosis,and investigated the correlation between the value of quantitative ultrasound bone mineral density and knee osteoarthritis in different grades. Results Quantitative ultrasound bone mineral density was positively correlated with dual energy X-ray bone density(r = 0.751,P < 0.05). The AUC of diagnosis of osteoporosis by quantitative ultrasound bone mineral density test with T<-2.5 was 0.774,95% CI was 0.676 and 0.791,specificity was 96.7%,sensitivity was 85.7% and Youden index was 82.4%.With an increase in the grades of Kellgren-Law-rence,the knee osteoarthritis gradually worsened.The T values of quantitative ultrasound bone mineral density and dual energy X-ray bone density increased gradually in negative direction,and the difference was statistically signifi-cant(P<0.001).Conclusions Quantitative ultrasound bone mineral density test has good specificity and sensi-tivity and can be used to screen patients with knee osteoarthritis. The more severe the knee osteoarthritis is,the easier to develop osteoporosis.

Objective To analyze the safety of renal transplant from donors with primary central nervous system (CNS) tumors.Methods We retrospectively analyzed the clinical data of 33 donors with primary CNS tumors and the 63 corresponding renal recipients between January 2013 and December 2016 in Tongji Hospital.Results The mean period from diagnosis as primary CNS tumor to donation was about (21.8± 46.4) months (range:0.5 to 192.0 months).The pathological classification of these tumors included gliomas,meningioma,medulloblastoma,etc.Besides,there were 10 donors with high-grade CNS malignancies.Eleven donors have ever been through at least one of the four treatments (craniotomy,V-P/V-A shunt,radiotherapy and chemotherapy),14 donors have undergone none,and the clinical data of rest were unavailable.All the 63 recipients got well renal function after transplant.During an average follow-up of (15.9 ± 8.2) months (range:2.7 to 35.5 months),one recipient got donor-derived rhabdoid tumor 4 months posttransplant,underwent comprehensive treatments,including allograft nephrectomy,radiotherapy,chemotherpy and returned to hemodialysis,while the 62 cases got no donor-derived tumors.Conclusion Tumor transmission of renal allograft from donors with primary CNS tumors is inevitable but with low risk,which means this kind of donors can be used with careful assessment,full informed consent and good balance between wait-list death and tumor transmission.

Objective To investigate the feasibility and safety of the single kidney transplantation from pediatric donors to adult recipients.Methods From May 2013 to January 2017,a total of 50 single kidney transplants from pediatric donation after citizen death (DCD) donors of age between 3 to 12 years to adult recipients were performed and the data were summarized.Results The average age of donors was 6.4 ± 2.5 years with an average donor weight of 19.1 ± 5.9 kg,and the average kidney length was 6.3 ± 0.6 cm.For the 50 adult recipients,the average age was 38.5 ± 12.1 years,the average body weight was 56.1 ± 13.1 kg,and the number of female patients was 26 (52％).All except 3 of these patients were transplanted for the first time.Delayed graft function (DGF) was observed in 15 patients (30％).The average value of eGFR among all the patients was rapidly increased in the first 3 months after transplantation and then steadily increased to (82.3 ± 13.4) mL· min-1·1.73 m-2 at 1 st year,followed by (83.8 ± 22.5) mL· min-1·1.73 m-2 at 2nd year.Four renal grafts developed acute rejection (8％),and 3 of them were successfully reversed by the treatment.Pulmonary infection occurred in 4 recipients,and 2 died.During a follow-up period of 19 months,uncensored grafts survival was 94％,and patients survival was 96％.Conclusion Excellent intermediate-term transplant outcome can be achieved by using single kidneys from pediatric donors elder than 3 years,which may shorten the waiting time in adult recipients and alleviate the contradictions in the absence of suitable pediatric recipients.

Wearable devices are used in the new design of the maternal health care system to detect electrocardiogram and oxygen saturation signal while smart terminals are used to achieve assessments and input maternal clinical information. All the results combined with biochemical analysis from hospital are uploaded to cloud server by mobile Internet. Machine learning algorithms are used for data mining of all information of subjects. This system can achieve the assessment and care of maternal physical health as well as mental health. Moreover, the system can send the results and health guidance to smart terminals.
Algorithms ; Clothing ; Electrocardiography ; Equipment Design ; Female ; Humans ; Internet ; Machine Learning ; Maternal Health ; Monitoring, Ambulatory ; instrumentation ; Telemedicine ; instrumentation