Objective: To retrospectively analyze the clinical data of 474 newborns with hyperbilirubinemia, and to investigate the clinical characteristics of hyperbilirubinemia caused by ABO hemolytic disease of the fetus and newborn (ABO-HDFN) and factors influencing the phototherapy duration. Methods: A total of 474 neonates with hyperbilirubinemia treated in the First Hospital of Lanzhou University from January 2019 to January 2023 were enrolled. Blood type identification and the standard serological tests (direct antiglobulin test, serum free antibody test, and antibody elution test) were performed for all neonates. Baseline clinical data were collected and analyzed. According to the results of the hemolysis tests, neonates were divided into hemolytic jaundice group and non-hemolytic jaundice group. Clinical indicators, including hemoglobin levels, length of hospital stay, and phototherapy duration, were compared between the two groups. A multiple linear regression model was used to explore clinical factors influencing the duration of phototherapy. Results: Among the 474 neonates with hyperbilirubinemia, 354 were diagnosed with ABO-HDFN (hemolytic group), while 120 were without ABO-HDFN (non-hemolytic group). The incidence of ABO-HDFN in neonates with blood type A (55.93%, 198/354) was significantly higher than those with blood type B (44.07%, 156/354) (P<0.05). Furthermore, neonates born to multiparous women had a significantly higher ABO-HDFN incidence (81.56%, 146/179) than first-born neonates (70.51%, 208/295) (P<0.05). Neonates in the hemolytic group had significantly lower hemoglobin levels (170.67±21.86 g/L vs 178.99±22.05 g/L, P<0.001), lower red blood cell counts (4.66±0.63×10 /L vs 4.89±0.59×10 /L, P<0.05), and lower hematocrit (50.05±6.56% vs 52.61±6.75%, P<0.05) compared to the non-hemolytic group. Additionally, the hemolytic group had significantly longer hospital stays (6 [5, 9] days vs 6 [4, 8] days), longer phototherapy duration (62 [38, 84.25] h vs 53 [34.25, 64.77] h), and higher frequency of jaundice episodes (9 [7, 13] times vs 8 [6, 12] times] compared to the non-hemolytic group (all P<0.05). Regression analysis indicated that a positive indirect Coombs test and multiparity were independent risk factors associated with prolonged phototherapy duration (P<0.05). Conclusion: ABO incompatibility is the leading cause of hemolytic disease in neonates, particularly in cases where the mother has blood type O and the neonate has blood type A. In such cases, close monitoring of bilirubin levels is strongly recommended. Multiparous pregnancies increase the risk of alloimmune hemolysis. Therefore, neonates born to multiparous women may require more frequent bilirubin monitoring and appropriate prenatal interventions when necessary. Additionally, changes in indicators such as hemoglobin level and red blood cell count should be closely monitored as early warning indicators for hemolytic anemia and bilirubin elevation.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To explore the chain mediating effect of basic activity of daily living and nutritional status the effects on comorbidity and frailty, so as to provide guidance for preventing and delaying the frailty of elderly patients with cardiovascular disease and abnormal glucose metabolism.Methods:The cross-sectional study method was adopted, 300 elderly patients with cardiovascular disease and abnormal glucose metabolism who were hospitalized in the cardiovascular medicine ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University, were selected as the study objects from January to August 2022, and were surveyed using General Information Questionnaire, Frailty Scale, Charlson Comorbidity Index Scale, Barthel Index Rating Scale and Mini Nutritional Assessment-Short Form were used to investigate them.Results:A total of 300 questionnaires were collected and 291 valid questionnaires were returned. Out of 291 patients, 167 were male and 124 were female, with an age of (69.55 ± 7.01) years. Comorbidities in elderly patients with cardiovascular disease and abnormal glucose metabolism were positively correlated with frailty ( r=0.414, P<0.01), and negatively correlated with basic activity of daily living and nutritional status ( r=-0.399, -0.373, both P<0.01). Basic activity of daily living was positively correlated with nutritional status ( r=0.575, P<0.01) and negatively correlated with frailty ( r=-0.825, P<0.01). Nutritional status was negatively correlated with frailty ( r=-0.695, P<0.01). The chain mediating model showed that comorbidities had a significant direct effect on frailty (effect value of 0.102), basic activity of daily living partially mediated between comorbidity and frailty (effect value of 0.125). Basic activity of daily living and nutritional status partially chained between comorbidity and frailty (effect value of 0.036). Conclusions:The chain mediating roles of basic activity of daily living and nutritional status between comorbidity and frailty was established. Healthcare professionals should pay attention to the improvement of basic activity of daily living in elderly patients with cardiovascular diseases and abnormal glucose metabolism, guide them to have a reasonable diet to achieve balanced nutrition, and delay the onset and development of frailties.

【Objective】 To investigate the serology and genotype identification method of B (A) subtype patients. 【Methods】 Test tube method (serology) was used to confirm the clinically difficult ABO blood group samples of 3 patients with ABO blood group; ABO blood group was genotyped by real-time PCR, and the ABO gene exon 1-7 was sequenced to determine the genotype. 【Results】 The forward and reverse blood typing result of three patients was B (A) subtype all with ABO genotype B/O2 and c.640A> G mutation on B allele of exon 7, which meets the characteristics of ABO * BA.04 genotype. 【Conclusion】 The combination of serological and genetic testing could identify difficult blood types such as ABO subtypes accurately and ensure the safety of clinical blood use.

OBJECTIVE To study the effects of the active component 17-hydroxy-jolkinolide B （HJB） of Euphorbia fischeriana on the proliferation and apoptosis of human triple-negative breast cancers （TNBC） MDA-MB-231 and MDA-MB-468 cells. METHODS MTT assay was adopted to detect the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation after treated with 0 （blank control），5，10，20，40，80 μmol/L HJB for 24， 48 and 72 h. Laser confocal microscope and flow cytometry were adopted to detect the apoptosis， mitochondrial membrane potential（MMP） and reactive oxygen species （ROS） of above 2 kinds of cells after treated with 0 （blank control）， 10，20，40 μmol/L HJB for 24 h. Western blot assay was used to detect the expressions of B cell lymphoma-2（ Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome-C （Cyt-C）， caspase-3， cleaved caspase- 3， caspase-9 and cleaved caspase-9. RESULTS Compared with blank control group， 5，10，20，40，80 μmol/L HJB could significantly increase the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation （P＜0.05）， in dose- and time- dependent trend. After 24 h treatment of HJB （10，20，40 μmol/L）， the apoptosis of above 2 kinds of cells increased， and the total apoptotic rate increased significantly （P＜0.05）； the mitochondrial membrane potential decreased significantly （P＜0.05）； the level of ROS increased significantly （P＜0.05）； the protein expressions of Bcl-2， caspase-3 and caspase-9 were decreased significantly （P＜ 0.05）， while the protein expressions of Cyt-C， Bax， cleaved caspase-3 and cleaved caspase-9 were increased significantly （P＜0.05）. CONCLUSIONS HJB can inhibit the proliferation of MDA-MB-231 and MDA-MB-468 cells， and induce their apoptosis.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective:To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus.Methods:This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13 3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared.Results:A total of 1 152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant ( Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion:The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.

Objective To observe the effect of miR-145 on pain threshold and explore the pos-sible underlying positive role of miR-145 in rats with diabetic neuropathic pain.Methods The total of 36 rats with diabetic neuropathic pain were randomly divided into three groups respectively with nor-mal control group (group N)(n=12 for each group):diabetic neuropathic pain(DNP)group (group D),DNP-NC group (group DN)and DNP-agomiR-145 group (group agomiR-145).The rats received agomiR-145 intrathecal injection in group agomiR-145 (10 μl,1×106TU/ml),or the negative control virus in group DN (10 μl,1×106TU/ml),or equal volume of normal saline in other two groups. Paw mechanical withdrawal threshold(MWT)and paw withdrawal latency(TWL)were measured on the day before intrathecal injection and day 1,days 3,7 and 14 after intrathecal injection.On the days 14 after pain-related behavioral test,the RNA expression of miR-145 in the dorsal root ganglion (DRG)was detected using reverse transcription-quantitative polymerase chain reaction(RT-PCR)as-say and the expression of Nav 1.8 in DRG were detected by fluorescent immunofluorescence.In addi-tion,a dual luciferase activity assay was used to testify the target genes of miR-145.Results MWT and TWL were decreased at 1 d before intrathecal injectionin groups D,DN and agomiR-145 than that in group N (P<0.05).The significant increase of MWT was observed in group agomiR-145 on day 3,7,14 than those in group D and group DN (P<0.05).TWL in group agomiR-145 was increased significantly on day 7 and day 14 compared with those in groups D and DN (P<0.05).Compared with group N,miR-145 expression level in DRG in groups D and DN were significantly lower (P<0.05).In addition,the protein expression of Nav1.8 was significantly increased in group D and DN compared with that in group N (P<0.05).Compared with groups D and DN,miR-145 expression was increased significantly and the expression of Nav1.8 in DRG was decreased significantly in group agomiR-145 (P<0.05).In addition,a dual luciferase reporter assay demonstrated that miR-145 can bind with the 3'-UTR region of Nav1.8 and regulate its expression.Conclusion Intrathecal agomiR-145 can effectively attenuate neuropathic pain of DNP rats,which may be related with down-regulation of Nav1.8 in DRG..

OBJECTIVEUsing simultaneous multi-gene mutation screening to investigate the new method molecular epidemiological basis of 225 patients with nonsyndromic hearing loss in Tianjin, and verifying the for simultaneous multi-gene mutation screening.

METHODSTwo hundred and twenty-five patients with severe non-syndromic deafness from Tianjin CDPF and Association of the Deaf were included in the study. The single nucleotide polymorphisms scan, (SNPscan) technique was used for screening the 115 spots mutations in three common deafness-related genes (GJB2, SLC26A4, mtDNA 12S rRNA) of patients with nonsyndromic hearing loss in Tianjin. We verified the results by Sanger sequencing.

RESULTSAmong the 225 patients, there were 111 cases of deafness caused by mutation (49.3%). Using this method, up to 50% of the patients in our study were identified to have hereditary HL caused by mutations in the three genes. 56 patients with the GJB2 mutations were detected (24.9%), including 30 cases of homozygous mutations (13.3%), 26 patients (11.6%) of compound heterozygous mutations, and 21 cases (9.33%) of single heterozygous mutations. 50 patients with the SLC26A4 mutations were detected (22.2%), including 22 cases of homozygous mutations(9.8%), 28 patients (12.4%) of compound heterozygous mutations, and 22 cases (9.8%) of single heterozygous mutations. mtDNA 12S rRNA A1555G mutation was detected in 5 patients (2.2%). mtDNA 12S rRNA 1494C>T mutation was not detected. We verified the results by Sanger sequencing. The accuracy of the sequencing results was 100%. The SNPscan cost eight hours and 160 yuan (each sample).

CONCLUSIONSApplying SNPscan technology can be accurate, rapid and cost-effective diagnostic screening in patients with hearing loss for etiology investigation. It is expected to become an effective means of large-scale genetic testing for hereditary deafness.

Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; methods ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Genetic Testing ; methods ; Heterozygote ; Homozygote ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Polymorphism, Single Nucleotide ; RNA, Ribosomal ; genetics