Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Objective To cultivate the ability of laboratory resident physicians in multiple aspects and enhance their post-competence for laboratory medicine.Methods The residents recruited into the Cancer Hospital of China Academy of Medical Sciences Laboratory Base were divided into junior residents and senior residents.According to the different training contents and objectives,the exploration of the hierarchically progressive training model was carried out,which mainly included three aspects:training plan,process training and process assessment.Results After the implementation of the hierarchical progressive training model,the average theoretical score and the average score in the skill operation examination of the residents increased to over 90 and 95,respectively.Meanwhile,the comprehensive clinical ability was also improved.Breakthroughs of teaching,scientific research and honor were achieved from"nothing"before the implementation to"something"after the implementation,and it actively promoted the improvement of the post-competency of the residents in laboratory medicine.Conclusion The application of the hierarchically progressive training mode in standardized training of residents in laboratory medicine could play a good role in promoting the training of post-competence for residents.

Objective:To investigate the clinical efficacy of radical resection of rectal cancer with different surgical approaches and influencing factors of postoperative complications.Methods:The retrospective study was conducted. The clinicopathological data of 3 418 patients who underwent radical resection of rectal cancer in the Second Affiliated Hospital of Harbin Medical University from July 2011 to September 2020 were collected. There were 2 060 males and 1 358 females, aged (61±11)years. Patients meeting the requirements of radical resection and surgical indications underwent surgeries choosing from open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery, and natural orifice specimen extraction surgery (NOSES). Observation indicators: (1) intraoperative and postoperative conditions of patients undergoing different surgical approaches; (2) comparison of preoperative clinical characteristics in patients undergoing different surgical approaches; (3) comparison of postoperative histopathological characteristics in patients undergoing different surgical approaches; (4) postoperative complications of patients undergoing different surgical approaches; (5) analysis of influencing factors of postoperative complications. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparisons between groups was analyzed using the Kruskal-Wallis rank test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Intraoperative and postoperative conditions of patients undergoing different surgical approaches. Of the 3 418 patients, 1 978 cases underwent open radical colorectal cancer sur-gery, 1 028 cases underwent laparoscopic radical colorectal cancer surgery and 412 cases underwent NOSES, respectively. The operation time, volume of intraoperative blood loss, cases with permanent stoma, preventive stoma or without fistula, time to postoperative first flatus, time to postoperative liquid food intake, cases transferred to intensive care unit after surgery, duration of postoperative hospital stay were 145(range, 55?460)minutes, 100(range, 30?1 000)mL, 435, 88, 1 455, 72(range, 10?220)hours, 96(range, 16?296)hours, 158, 10(range, 6?60)days, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 175(range, 80?450)minutes, 50(range, 10?800)mL, 172, 112, 744, 48(range, 14?120)hours, 72(range, 38?140)hours, 17, 9(range, 4?40)days, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 180(range, 80?400)minutes, 30(range, 5?500)mL, 0, 45, 367, 48 (range, 14?144)hours, 72(range, 15?148)hours, 1, 6(range, 3?30)days, respectively, in patients undergoing NOSES. There were significant differences in the above indicators among the patients undergoing different surgical approaches ( H=291.38, 518.56, χ2=153.82, H=408.86, 282.97, χ2=78.66, H=332.30, P<0.05). (2) Com-parison of preoperative clinical characteristics in patients undergoing different surgical approaches. The gender, age, body mass index, cases with diabetes, cases with hypertension, cases with coronary heart disease, cases with anemia, cases with hypoproteinemia, cases with intestinal obstruction, tumor location, preoperative carcinoembryonic antigen, preoperative CA19-9 showed significant differences among patients undergoing open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery and NOSES ( P<0.05). (3) Comparison of postoperative histopathological characteris-tics in patients undergoing different surgical approaches. Tumor histological type, tumor differentiation degree, tumor diameter, number of lymph node detected, nerve invasion, vascular invasion, lymph node invasion, tumor T staging, tumor N staging, tumor M staging, tumor TNM staging showed significant differences among patients undergoing open radical colorectal cancer surgery, laparos-copic radical colorectal cancer surgery and NOSES ( P<0.05). (4) Postoperative complications of patients undergoing different surgical approaches. Cases with postoperative complications as anastomotic leakage, abdominal infection, intestinal obstruction, anastomotic bleeding, incision complications, pulmonary infection, other complications were 52, 21, 309, 8, 130, 51, 59, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 33, 17, 75, 3, 45, 58, 9, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 13, 4, 8, 0, 11, 10, 15, respectively, in patients undergoing NOSES. There were significant differences in the intes-tinal obstruction, incision complications, pulmonary infection, other complications among patients undergoing different surgical approaches ( χ2=122.56, 13.33, 20.44, 15.59, P<0.05) and there was no significant difference in the anastomotic leakage, abdominal infection, anastomotic bleeding among patients undergoing different surgical approaches ( χ2=0.96, 2.21, 3.08, P>0.05). (5) Analysis of influencing factors of postoperative complications. ① Analysis of influencing factors of intestinal obstruction in patients with radical resection of rectal cancer. Age as 20?39 years and 40?59 years, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of intestinal obstruction in patients with radical resection of rectal cancer ( odds ratio=0.46, 0.59, 0.43, 0.13, 95% confidence interval as 0.21?1.00, 0.36?0.96, 0.33?0.56, 0.06?0.27, P<0.05). ② Analysis of influencing factors of incision complications in patients with radical resection of rectal cancer. Body mass index as 24.0?26.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of incision complications in patients with radical resection of rectal cancer ( odds ratio=0.24, 0.63, 0.46, 95% confidence interval as 0.11?0.51, 0.44?0.89, 0.24?0.87, P<0.05). ③ Analysis of influencing factors of pulmonary infection in patients with radical resection of rectal cancer. The surgical approach as laparoscopic radical colorectal cancer surgery was an independent risk factor of pulmonary infection in patients with radical resection of rectal cancer ( odds ratio=2.15, 95% confidence interval as 1.46?3.18, P<0.05), and tumor TNM staging as 0?Ⅰ stage was an independent protective factor ( odds ratio=0.10, 95% confidence interval as 0.01?0.88, P<0.05). ④ Analysis of influencing factors of other complica-tions in patients with radical resection of rectal cancer. Age as 20?39 years, 40?59 years, 60?79 years, body mass index as <18.5 kg/m 2, 18.5?23.9 kg/m 2, 24.0?26.9 kg/m 2, 27.0?29.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery were independent protective factors of other complications in patients with radical resection of rectal cancer ( odds ratio=0.10, 0.29, 0.37, 0.08, 0.22, 0.35, 0.32, 0.29, 95% confidence interval as 0.01?0.81, 0.13?0.64, 0.17?0.78, 0.02?0.40, 0.09?0.52, 0.15?0.83, 0.12?0.89, 0.14?0.59, P<0.05). Conclusions:Compared to laparoscopic radical colorectal cancer surgery and NOSES, open radical colorectal cancer surgery has wide indication and short operation time, but less perioperative treatment effect. Laparoscopic radical colorectal cancer surgery and NOSES can achieve better surgical result and less postoperative complication when patients meeting surgical indications.

Objective:To analyze the genetic etiology and prognosis in fetuses with increased nuchal translucency (NT) in order to assist in the clinical prenatal genetic counseling and diagnosis.Methods:This study retrospectively enrolled 1 658 cases of singleton pregnancy (<35 years old) receiving invasive prenatal diagnosis, including karyotype analysis and/or chromosome microarray analysis or copy number variation (CNV) sequencing, due to NT value ≥2.5 mm in the first trimester in Henan Provincial People's Hospital from August 2014 to December 2021. They were divided into different groups according to the thickness of NT (≥2.5-<3.0, ≥3.0-<3.5, ≥3.5-<4.5, ≥4.5-<5.5, ≥5.5-<6.5 and ≥6.5 mm groups) and abnormal ultrasound findings (isolated increased NT group, increased NT complicated by soft markers/non-severe structural abnormality group and increased NT complicated by severe structural abnormality group). The results of invasive prenatal diagnosis and pregnancy outcomes were compared between different groups using Chi-square test and trend Chi-square test. Results:The detection rates of numerical abnormalities of chromosomes were 15.8% (262/1 658) and 17.6% (252/1 431) when the NT thickness cut-off value were 2.5 mm or 3.0 mm, respectively. Overall, the detection rate of numerical abnormalities of chromosomes increased with thickness of NT ( χ2trend=180.75, P<0.001), ranging from 6.6% (44/671) in the NT≥2.5-<3.5 mm group to 45.6% (113/248) in the NT≥5.5 mm group. The incidence of pathogenic/likely pathogenic CNV(P/LP CNV) did not increased with NT thickness ( χ2trend=3.26, P=0.071), and the highest detection rate was observed in the NT≥4.5-<5.5 mm group (9.0%, 19/211). The detection rate of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥2.5-<3.0 mm group and NT≥3.0-<3.5 mm group were 5.3% (10/188) and 9.6% (36/375), respectively, however, the difference was not statistically significant ( χ2=3.06, P=0.080). The detection rates of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥3.5-<4.5 mm group and NT≥2.5-<3.0 mm complicated by soft markers/ non-severe structural abnormality group were 12.7% (52/410) and 24.1% (7/29), respectively, and the risk were 2.6 times (95% CI: 1.3-5.2) and 5.7 times (95% CI: 2.0-16.4) of the isolated NT≥2.5-<3.0 mm group, respectively. The pregnancy termination rate increased with the NT thickness ( χ2trend=304.42, P<0.001), ranging from 10.8% (23/212) in the NT≥2.5-<3.0 mm group to 90.7% (117/129) in the NT≥6.5 mm group. After exclusion of the pregnancies terminated due to numerical abnormalities of chromosomes and P/LP CNV, 87.6% (862/984) of the fetus with increased NT were born alive. Conclusions:The detection rate of numerical abnormalities of chromosomes increases with the thickness of NT. Invasive prenatal diagnosis is required for non-advance aged singleton pregnant women when fetuses present with isolated NT≥2.5 mm with or without soft markers/structural abnormalities.

Background::Acute kidney injury (AKI) is a common complication in patients, especially elderly patients, who undergo cardiac surgery with cardiopulmonary bypass. Studies have indicated a protective role of autophagy in AKI. However, the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood. In this study, we aimed to test the hypothesis that exosomal microRNAs (miRNAs) regulate autophagy in tubular epithelial cells after AKI.Methods::Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery, and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing. The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses. Renal tubular epithelial cell line (HK-2 cells) was cultured and hypoxia/reoxygenation (H/R) model was established, which is an in vitro renal ischemia/reperfusion (I/R) model. We used Western blot analysis, cell viability assay, transfection, luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy. Results::miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery. Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins, including Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3II), and prolonged the autophagic response in HK-2 cells after H/R treatment. These effects were achieved mainly via increases in the exosomal miR-590-3p levels, and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction.Conclusion::Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner, which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.