Objective To investigate the gene expression profile in rat pancreatic ductal stem cells(PDSCs)when induced to differentiate into insulin-secreting cells(IPCs),with the goal of identifying key genes involved in this differentiation process.Methods The expanded PDSCs were categorized into a normal control(NC)group and an induced(Tre)group.PDSCs continued expansion culture in NC group,and cultured in induction medium for 28 days to facilitate the differentiation of PDSCs into IPCs in Tre group.Dithizone staining was employed to morphologically assess whether the cells exhibited a reddish-brown coloration,indicating a positive result.The immunofluorescence staining method was used to detect the expression of insulin(Ins)and PDX1 in the cells following induction.Additionally,ELISA was conducted to measure the Ins release from IPCs,thereby verifying the responsiveness of the induced cells to glucose-stimulated Ins secretion.Concurrently,cells were collected on induction days 0 and 28 for RNA sequencing(RNA-seq),and differentially expressed genes(DEGs)were analyzed and functionally annotated.The analysis revealed that regulatory factor X3(RFX3)was overexpressed in PDSCs,and the impact of RFX3 upregulation on differentiation induction was subsequently verified.Results Compared with NC group,DTZ staining was positive,PDX1 and Ins proteins were expressed,and an increased release of Ins in response to sugar stimulation was demonstrated in the Tre group.RNA-seq analysis identified 4270 DEGs,and functional enrichment analysis utilizing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases revealed associations with Ins response,positive regulation of Ins secretion,pancreatic endocrine cell development,and overall pancreatic development.Additionally,functionally related genes such as ALDHA2,CREB5,EIF6,FOXO1,RFX3,WNT5a,OGT,GPR39,SMAD6,and TRPM2 were identified,indicating involvement in the cell cycle,TGF-β1 signaling pathway,FOXO signaling pathway,and Wnt signaling pathway in the regulation of the differentiation of pancreatic ductal stem cells(PDSCs)into insulin-producing cells(IPCs).Furthermore,the upregulation of RFX3 can inhibit the expression of TGF-β1 within 72 hours,thereby promoted the formation and release of Ins from insulin-positive cells.Conclusions Multiple genes and signaling pathways associated with pancreatic β-cell function collectively regulate the differentiation of rat PDSCs into IPCs.Notably,the upregulation of RFX3 enhances this differentiation process.

Objective To investigate the gene expression profile in rat pancreatic ductal stem cells(PDSCs)when induced to differentiate into insulin-secreting cells(IPCs),with the goal of identifying key genes involved in this differentiation process.Methods The expanded PDSCs were categorized into a normal control(NC)group and an induced(Tre)group.PDSCs continued expansion culture in NC group,and cultured in induction medium for 28 days to facilitate the differentiation of PDSCs into IPCs in Tre group.Dithizone staining was employed to morphologically assess whether the cells exhibited a reddish-brown coloration,indicating a positive result.The immunofluorescence staining method was used to detect the expression of insulin(Ins)and PDX1 in the cells following induction.Additionally,ELISA was conducted to measure the Ins release from IPCs,thereby verifying the responsiveness of the induced cells to glucose-stimulated Ins secretion.Concurrently,cells were collected on induction days 0 and 28 for RNA sequencing(RNA-seq),and differentially expressed genes(DEGs)were analyzed and functionally annotated.The analysis revealed that regulatory factor X3(RFX3)was overexpressed in PDSCs,and the impact of RFX3 upregulation on differentiation induction was subsequently verified.Results Compared with NC group,DTZ staining was positive,PDX1 and Ins proteins were expressed,and an increased release of Ins in response to sugar stimulation was demonstrated in the Tre group.RNA-seq analysis identified 4270 DEGs,and functional enrichment analysis utilizing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases revealed associations with Ins response,positive regulation of Ins secretion,pancreatic endocrine cell development,and overall pancreatic development.Additionally,functionally related genes such as ALDHA2,CREB5,EIF6,FOXO1,RFX3,WNT5a,OGT,GPR39,SMAD6,and TRPM2 were identified,indicating involvement in the cell cycle,TGF-β1 signaling pathway,FOXO signaling pathway,and Wnt signaling pathway in the regulation of the differentiation of pancreatic ductal stem cells(PDSCs)into insulin-producing cells(IPCs).Furthermore,the upregulation of RFX3 can inhibit the expression of TGF-β1 within 72 hours,thereby promoted the formation and release of Ins from insulin-positive cells.Conclusions Multiple genes and signaling pathways associated with pancreatic β-cell function collectively regulate the differentiation of rat PDSCs into IPCs.Notably,the upregulation of RFX3 enhances this differentiation process.

Bariatric surgery is an important means to achieve weight loss in patients and improve obesity-related metabolic disorders. Evaluating the treatment compliance of patients after bariatric surgery can help medical and nursing staff develop personalized intervention plans. This paper summarizes the current status, assessment tools, and comparison of assessment tools of patient treatment compliance after bariatric surgery, providing a basis for medical and nursing staff to reasonably select treatment compliance assessment tools for patients after bariatric surgery.

Objective: To investigate the preliminary screening results of Alzheimer's disease (AD) among the elderly in Ningbo City, Zhejiang Province and analyze the influencing factors, so as to provide insights into prevention and control of AD in the elderly. Methods: A multi-stage stratified proportional sampling method was used to select the registered residents aged 60 years and older in Ningbo City as subjects. Demographic characteristics, lifestyle factors, physical conditions and social activities of the subjects was evaluated with questionnaires. AD was screened using the Mini-Mental State Examination (MMSE), and factors affecting the positive rate of AD preliminary screening were identified using a multivariable logistic regression model. Results: A total of 34 027 elderly residents were investigated, with an mean age of (71.71±6.89) years. There were 15 115 males (44.42%) and 18 912 females (55.58%), 16 146 residents living in rural areas (47.45%) and 17 881 residents living in urban areas (52.55%). The positive rate of AD preliminary screening was 7.28% (2 476 cases). Multivariable logistic regression analysis showed that age (70 to 74 years, OR=1.357; 75 to 79 years, OR=1.807; 80 to 84 years, OR=2.782; 85 years and older, OR=4.907), gender (female, OR=1.118), residence (urban areas, OR=0.713), marital status (unmarried, OR=3.078; widowed/separated/divorced, OR=1.301), educational level (primary school, OR=0.629; junior high school and above, OR=0.609), occupation before retirement (others, OR=0.741), family genetic history (no, OR=0.651), household disposable monthly income (1 000 to 1 999 Yuan, OR=0.636; 2 000 to 2 999 Yuan, OR=0.569; 3 000 Yuan and above, OR=0.448), exercise (seldom, OR=0.855; regular, OR=0.780), number of chronic diseases (2~5, OR=1.328), hearing loss (no, OR=0.764), smell loss (no, OR=0.615), chronic constipation (no, OR=0.696), major negative life events (no, OR=0.804), subjective memory loss (no, OR=0.583), sleep quality (general, OR=0.640; good, OR=0.616), living style (living with spouse, OR=0.300; living alone, OR=0.315; living with children, OR=0.350) and social activities (2-3 times/week, OR=0.584; 4 times/week and more, OR=0.409) were factors affecting the positive rate of AD preliminary screening. Conclusions The positive rate of AD preliminary screening among the elderly in Ningbo City is relatively high. Age, gender, economic conditions, exercise, social activities and physical conditions were factors affecting the positive rate of AD preliminary screening.

Objective:To evaluate the safety and efficacy of bortezomib plus highdose melphalan (L-phenylalanine nitrogen mustard) (Bor-HDM) pretreatment regimen for multiple myeloma (MM) with autologous hematopoietic stem cell transplantation (ASCT).Methods:From August 2008 to December 2021, the relevant clinical data were retrospectively reviewed for 58 MM patients undergoing MM transplantation.The conditioning regimens were Bor-HDM (n=36) and HDM (n=22). Non-hematopoietic adverse reactions, hematopoietic reconstruction time, remission rate post-ASCT and minimal negative rate of residual disease (MRD) on flow cytometry within 3 months post-ASCT and survivals were analyzed.Results:In Bor-HDM and HDM groups, median time of neutrophil engraftment was 12(8-30) and 11(8-29) day and median time of platelet reconstitution 16(8-33) and 16(7-32) day respectively.There was no significant inter-group difference ( P=0.890, P=0.638). In Bor-HDM group, the most common non-hematological adverse reactions were nausea (n=21, 58.0%) and diarrhea (n=11, 30.6%). There was no transplant-related death.Complete remission (CR) rate was (25/36, 69.4%) versus (9/22, 40.9%). The inter-group difference was statistically significant ( P=0.032). Median follow-up period was 29.0(2.0-91.0) vs. 20.5(5.0-114.0) month, 3-year progression-free survival(PFS)62.1% vs. 39.7% and 3-year overall survival(OS) 83.8% vs. 62.5%.There were relapse (n=10 vs.10) and death (n=6 vs. 7). Median PFS in Bor-HDM and HDM groups was non-attained and 27 months( P=0.047) and median OS time non-attained and 40 months respectively ( P=0.282). Multivariate analysis revealed that CR was an independent risk factor for PFS ( HR=28.896, 95% CI: 6.130-136.198, P<0.001). Non-CR was an independent risk factor for OS ( HR=3.843, 95% CI: 1.334-11.071, P=0.013; HR=28.595, 95% CI: 6.273-130.355, P<0.001). Conclusions:Bor-HDM pretreatment regimen of ASCT is both safe and efficacious for MM patients.

Syndrome of resistance to thyroid hormone(RTH)is a rare hereditary thyroid disease with various clinical manifestations and laboratory findings. RTH could be misdiagnosed and mistreated, resulting in aggravation of the disease. We reviewed the medical records of a patient with RTH over the past six years. In addition, we provided a summary of latest progress for RTH to help the clinicians to improve the understanding of the disease.

Among infertile patients treated with assisted reproductive technology (ART), some patients have insulin resistance (IR), and IR affects the outcome of ART, which may be one of the reasons of repeated implantation failure (RIF). This article aims to provide an overview of the research progress on the impact of IR on assisted reproduction, and provide a theoretical basis for the treatment of RIF caused by IR.

Among infertile patients treated with assisted reproductive technology (ART), some patients have insulin resistance (IR), and IR affects the outcome of ART, which may be one of the reasons of repeated implantation failure (RIF). This article aims to provide an overview of the research progress on the impact of IR on assisted reproduction, and provide a theoretical basis for the treatment of RIF caused by IR.

ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.