1.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
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.
2.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
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.
3.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
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.
4.Directing the surgical treatment of Crohn's disease within treat-to-target and disease clearance concept
Zhenya SUN ; Zhenxing ZHU ; Weiwei WEN ; Yuxia GONG ; Bolin YANG ; Weiming ZHU
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):274-278
Crohn's disease (CD) is a chronic progressive inflammatory bowel disease. With the introduction of the "treat-to-target (T2T) " concept, the treatment goals for CD have become clearer and more specific. Traditional surgical treatment for CD typically follows a "complication-driven" approach, in which surgery is usually performed only after severe complications, such as bowel obstruction, fistulas, perforation, or cancer have occurred. The emergence of the treat-to-target strategy and the concept of disease clearance has transformed the surgical treatment of CD from a "passive rescue" model to an "active intervention" approach. Treatment goals have shifted from merely addressing complications and improving symptoms to achieving both short and long-term therapeutic objectives within the framework of treat-to-target. Achieving these goals helps to prevent CD-related complications, delay disease progression, reduce the risk of recurrence and malignancy, and improve the quality of life.
5.Clinical characteristics and prognosis analysis of Crohn's disease complicated with secondary upper gastrointestinal fistulas
Jie XU ; Ming DUAN ; Jiajia ZHAO ; Yi LI ; Weiming ZHU
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):303-309
Objective:To evaluate the clinical characteristics of Crohn's disease (CD) patients with secondary upper gastrointestinal fistulas and analyze risk factors for recurrence.Methods:A restrospective observational research method was performed. Clinical data of CD patients with secondary upper gastrointestinal fistulas treated at Eastern Theater General Hospital of PLA from January 2010 to August 2024 were analyzed. Based on postoperative recurrence of upper gastrointestinal fistulas, the patients were divided into recurrence group and non-recurrence group. Differences in clinical data between the two groups were compared, and further multivariate Logistic regression analysis was used to identify the risk factors for fistula recurrence.Results:A total of 72 CD patients with secondary upper gastrointestinal fistulas were included, consisting of 48 males and 24 females, with a mean age of 39±12 years and a disease duration of 97±56 months, accounting for 2.8% of all CD patients undergoing surgeries during the same period. Among these patients, 75 upper gastrointestinal fistulas from 72 patients were identified, including 67 patients of simple duodenal fistula, 2 of simple gastric fistula, and 3 of double fistulas (2 of double duodenal fistulas and 1 of duodenal fistula combined with gastric fistula) .The preoperative diagnostic positivity rates were 55.6% (40/72) for gastroscopy, 54.2% (39/72) for upper gastrointestinal contrast imaging, 22.2% (16/72) for abdominal CT, and 22.2% (16/72) for colonoscopy. A history of biologic therapy was present in 33.3% (24/72) of patients, but none achieved fistula healing. All 72 patients underwent surgical treatment, with primary lesion surgical approaches including resection with anastomosis (37 patients, 51.4%) and resection with stoma (35 patients, 48.6%). Except for one gastric fistula treated by resection, all other fistulas underwent primary repair. During a median follow-up of 69 (40, 113) months, 8 patients (11.1%) required reoperation due to recurrent upper gastrointestinal fistulas (classified as the recurrence group), while the remaining 64 patients were assigned to the non-recurrence group. Univariate analysis revealed that the recurrence group had a higher proportion of patients aged 30-40 years ( P = 0.003), malnutrition ( P = 0.040), and anastomosis near the duodenum ( P = 0.047), but a lower proportion of postoperative biologic use ( P = 0.007) .Multivariate Logistic regression analysis showed that malnutrition and anastomosis near the duodenum were not the risk factors for duodenal fistula recurrence (both P > 0.05) . Conclusions:Upper gastrointestinal fistulas secondary to CD are rare, predominantly presenting as simple duodenal fistulas. Diagnosis primarily relies on gastroscopy and gastrointestinal contrast imaging. Biologic therapy shows poor efficacy, and most patients do not recur after the primary repair surgery of duodenal fistulas.
6.Identify the factors associated with treatment-free remission outcomes after imatinib discontinuation in children and adolescent patients with chronic myeloid leukemia
Huifang ZHAO ; Qian JIANG ; Weiming LI ; Yu ZHU ; Bingcheng LIU ; Qingshu ZENG ; Shuxia GUO ; Lixin LIANG ; Chunlei ZHANG ; Yingling ZU ; Yongping SONG ; Yanli ZHANG
Chinese Journal of Hematology 2025;46(9):800-805
Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.
7.Impact of Antibody Immune Response and Immune Cells on Osteoporosis and Fractures
Kangkang OU ; Jiarui CHEN ; Jichong ZHU ; Weiming TAN ; Cheng WEI ; Guiyu LI ; Yingying QIN ; Chong LIU
Clinics in Orthopedic Surgery 2025;17(3):530-545
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.
8.Analysis of the safety and associated risk factors of rush immunotherapy in 316 patients with allergic rhinitis
Mengyi WEI ; Xinhua ZHU ; Yating XIAO ; Weiming LUO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(8):954-960
Objective:To assess the safety and to identify risk factors associated with systemic adverse effects (SAEs) during the dose-escalation phase of rush immunotherapy (RIT) in patients with allergic rhinitis (AR).Methods:A retrospective analysis was conducted in 316 house dust mite-allergic patients diagnosed with AR who underwent RIT at the Second Affiliated Hospital of Nanchang University between February 2012 and August 2024, including 206 males and 110 females aging from 5 to 58 years old. The number of patients experiencing SAEs, the frequency of SAE incidents, and the severity grades of SAEs during the dose-escalation phase were analyzed. Associations between SAE occurrence and 19 potential factors, including demographic characteristics, serological parameters, and pulmonary function parameters, were investigated. Data were analyzed using IBM SPSS Statistics version 26.0.Results:Among the 316 patients, 4 358 RIT injections were administered during the dose-escalation phase. SAEs occurred in 45 patients (14.24%, 45/316), accounting for 57 distinct SAE incidents. The SAE incidence rate per injection was 1.31%. Of the 57 SAEs, 34 (59.65%) were Grade Ⅰ, 5 (8.77%) were Grade Ⅱ, and 18 (31.58%) were Grade Ⅲ. No Grade Ⅳ or Ⅴ SAEs were observed. SAE occurrence demonstrated significant associations with: age ( Z=-2.73, P=0.006), body mass index (BMI; t=4.08, P<0.001), skin prick test reaction intensity ( χ2=10.34, P=0.006), eosinophil count ( Z=-2.19, P=0.028), eosinophil percentage ( Z=-2.59, P=0.010), forced expiratory volume in one second (FEV?; Z=-2.04, P=0.042), peak expiratory flow (PEF; Z=-2.44, P=0.015). Multivariate logistic regression analysis identified BMI as an independent risk factor for SAEs ( OR=0.86; 95% CI: 0.75-0.99; P=0.034). Conclusions:During the RIT dose-escalation phase for house dust mite-allergic AR patients, the incidence of SAEs was approximately 1.31% per injection. SAEs were predominantly mild (Grade Ⅰ), consistent with a favorable overall safety profile. BMI was identified as a statistically significant risk factor for SAE occurrence.
9.Expert Consensus on Nutrition Therapy for Inflammatory Bowel Disease(the Third Edition)
Weiming ZHU ; Weiguo DONG ; Minhu CHEN ; Kaichun WU
Chinese Journal of Gastroenterology 2025;30(3):152-172
The risk and incidence of malnutrition among patients with inflammatory bowel disease(IBD)are significantly higher than those in the general population,which affect the therapeutic efficacy and prognosis of patients.Clinical nutrition plays an important role in the treatment of IBD,and with the fact that there have been many studies on the clinical practice of nutrition therapy in IBD both domestically and abroad in recent years,it is necessary to update the expert consensus on nutrition therapy for IBD and provide the latest guidance for clinical practice.This consensus is drafted and revised by experts from Inflammatory Bowel Disease Group of Chinese Society of Gastroenterology,Gastroenterology and Nutrition Cooperative Group of Chinese Society of Parenteral and Enteral Nutrition,and Nutrition Support and Treatment Collaboration Group of Chinese Society of Gastroenterology,Chinese Medical Association.It combines both expert consensus abroad and Chinese expert consensus on nutrition support therapy in inflammatory bowel disease(the second edition),aiming to reflect the latest concepts and research progress,and provide standardized guidance for nutrition therapy of IBD.In order to be consistent with the professional terminology adopted by international authoritative nutrition academic organizations,especially considering the unique role of clinical nutrition in the treatment of IBD,this consensus is hereby renamed as Expert consensus on nutrition therapy for inflammatory bowel disease.
10.Diagnostic value of multi-slice spiral CT pulmonary angiography combined with D-dimer testing for pulmonary embolism in patients with different revised Geneva scores
Mengying ZHU ; Guojun LU ; Weiming LI
Chinese Journal of Primary Medicine and Pharmacy 2025;32(9):1355-1360
Objective:To investigate the diagnostic value of D-dimer (D-D) testing combined with multi-slice spiral CT pulmonary angiography (MSCTPA) in patients with pulmonary embolism (PE) based on the modified Geneva score.Methods:This study adopted a prospective design. Ninety-six patients with suspected pulmonary embolism (PE) who received treatment at Jinhua Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, from January to December 2024, were included in this study. The modified Geneva score was used to assess the clinical probability and severity of PE in these patients. Based on their modified Geneva scores, the patients were divided into high-risk, moderate-risk, and low-risk groups. All patients underwent both MSCTPA and D-D testing. The diagnostic value of D-D testing and MSCTPA, both individually and in combination, for PE among patients with different modified Geneva scores was evaluated.Results:Clinical diagnosis confirmed PE in 55 of the 96 suspected cases, with a positivity rate of 57.29% (55/96). According to the revised Geneva score, the high-risk group had the highest PE positivity rate (91.67%, 11/12), followed by the moderate-risk group (59.70%, 40/67) and the low-risk group (23.53%, 4/17). In the moderate-risk group, MSCTPA showed a significantly higher positive confirmation rate than negative confirmation rate ( χ2 = 12.32, P < 0.001), with a positive predictive value of 73.91% (34/46), a negative predictive value of 71.43% (15/21), specificity of 55.56% (15/27), sensitivity of 85.00% (34/40), and accuracy of 73.13% (49/67). D-D testing in the moderate-risk group also demonstrated a higher positive confirmation rate ( χ2 = 9.04, P < 0.05), with a positive predictive value of 72.73% (32/44), negative predictive value of 65.22% (15/23), specificity of 55.56% (15/27), sensitivity of 80.00% (32/40), and accuracy of 70.15% (47/67). The combination of D-D testing and MSCTPA significantly increased the positive confirmation rate for patients in the moderate-risk group compared with the negative confirmation rate ( χ2 = 28.78, P < 0.001). D-D testing combined with MSCTPA showed a positive predictive value of 83.72% (36/43), a negative predictive value of 83.33% (20/24), specificity of 74.07% (20/27), sensitivity of 90.00% (36/40), and accuracy of 83.58% (56/67) for patients in the moderate-risk group. Conclusions:D-D testing combined with MSCTPA demonstrates high diagnostic value for PE in patients assessed by the revised Geneva score, particularly for patients who are at moderate risk for PE.

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