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.

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.

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 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.

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 provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.

OBJECTIVE: To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening. METHODS: 7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up. RESULTS: Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ ²=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ ²=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ ²=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. CONCLUSION Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.
Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Genomics ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnant Women ; Prenatal Diagnosis/methods* ; Technology