BACKGROUND:Macrophages exhibit distinct pro-inflammatory and anti-inflammatory phenotypes.Through tissue engineering techniques,their phenotype transition has made them one of the most studied immune cells in bone injury repair.Recent studies have found that neutrophils also play a significant role in bone injury repair processes,but there is currently no such review available.OBJECTIVE:To summarize the current role of neutrophils in fracture healing and interventions targeting neutrophils to promote fracture healing.METHODS:We searched the Web of Science,PubMed,WanFang Data,and CNKI databases from January 2000 to February 2024 with the key words of"neutrophil,fracture healing,bone damage,bone repair,bone remodeling"in Chinese and English.Literature screening was conducted based on inclusion and exclusion criteria,resulting in a final selection of 72 articles for review.RESULTS AND CONCLUSION:(1)The history of neutrophils has been long,with their importance initially overlooked due to a lack of staining techniques.In 1900,Paul Ehrlich's invention of triacid staining distinguished neutrophils,marking the beginning of research in this field.(2)Under normal conditions,neutrophils migrate to various organs to assist in their physiological functions.In pathological states,neutrophils exert their antimicrobial effects through phagocytosis,degranulation,and the formation of neutrophil extracellular traps.(3)Neutrophils primarily participate in the early hematoma inflammation stage of fracture healing by releasing cytokines to recruit other immune cells and mesenchymal stem cells.They also produce fibrinogen to promote hematoma formation and establish a local microenvironment.(4)Neutrophils transform into two distinct subtypes,N1 and N2,at different stages of fracture healing,coordinating with each other to promote bone repair.(5)Neutrophils recruited to the fracture site participate in the healing process by secreting cytokines such as tumor necrosis factor-alpha,interleukin-6,interleukin-10,fibroblast growth factor-2,monocyte chemoattractant protein-1,and platelet-derived growth factor.(6)Neutrophils regulate osteogenesis/osteolysis balance through interactions with the main cellular components involved in different stages of fracture healing.(7)Similar to the widespread research and application of tissue engineering techniques in modulating macrophage polarization in fracture healing,interventions targeting neutrophils to promote fracture healing hold promising prospects for the future.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

OBJECTIVES: To construct a nomogram for predicting the efficacy of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (aNSCLC) by integrating chest CT radiomics signature that reflects the tumor microenvironment (TME) and clinical parameters of the patients. METHODS: Transcriptomic and CT imaging data from TCGA, GEO and TCIA databases were integrated for weighted gene co-expression network analysis (WGCNA) of the GEO cohort to identify the immunotherapy-related genes (IRGs) associated with ICIs response. A prognostic model was built using these IRGs in the TCGA cohort to assess immune microenvironment features across different risk groups. Radiomics features were extracted from TCIA lung_3 cohort using PyRadiomics, and 94 features showing strong association with IRGs (|r|>0.4) were selected. A retrospective cohort consisting of 210 aNSCLC patients receiving first-line ICIs at Guangdong Provincial People's Hospital was analyzed and divided into training (n=147) and validation (n=63) groups. Least absolute shrinkage and selection operator was used for radiomic features selection, and logistic regression was applied to construct a combined clinical-radiomic model and nomogram for predicting ICIs therapy response. The performance of the model was evaluated using ROC curve, calibration curve, and decision curve analysis. RESULTS: WGCNA identified 84 IRGs enriched in immune activation pathways. The combined model outperformed individual models in both the training (AUC=0.725, 95% CI: 0.644-0.807) and validation cohorts (AUC=0.706, 95% CI: 0.577-0.836). Calibration curve and decision curve analyses confirmed the clinical efficacy of the nomogram for predicting ICIs therapy response in aNSCLC patients. CONCLUSIONS The genomic-radiomic-clinical multidimensional predictive framework established in this study provides an interpretable biomarker combination and clinical decision-making tool for evaluating ICIs efficacy in aNSCLC, potentially facilitating personalized immunotherapy decision-making.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Tumor Microenvironment ; Lung Neoplasms/therapy* ; Immunotherapy ; Tomography, X-Ray Computed ; Nomograms ; Retrospective Studies ; Immune Checkpoint Inhibitors/therapeutic use* ; Prognosis ; Male ; Female ; Radiomics

Objective:To establish a quality standard system for Descurainiae Semen under the requirements of German Pharmaceutical Codex (DPC); To compare the similarities and differences between DPC and the Pharmacopoeia of the People's Republic of China regarding the establishment of a quality standard system for TCM medicinal materials. Methods:Based on the requirements of DPC, and referring to the relevant methods of Pharmacopoeia of the People's Republic of China, the quality of 30 batches of Descurainiae Semen samples were assessed by observing the appearance and microscopic characteristics and determining their loss on drying, total ash content, and ash insoluble in hydrochloric acid. A TLC identification method was established based on a silica gel G TLC plate, using a developing agent composed of ethyl acetate, formic acid, and water in the ratio of 7:1.5:2.5 ( V/ V/ V). The method utilized rutin and quercetin as indicators for the System Suitability Test (SST), and took quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside and isorhamnetin 3-O-β-D-glucose-7-O-β-D-gentiobioside as the index. Based on the content determination method for Descurainiae Semen in the Pharmacopoeia of the People's Republic of China, a content determination method was established with quercetin-3-O-β-D-glucose-7-O-β- D-gentiobioside as the index. Results:The loss on drying for the 30 batches of samples ranged from 6.15% to 12.0%, with the total ash content ranged from 3.17% to 9.44%, and the ash insoluble in hydrochloric acid content ranged from 0.14% to 4.82%. The resolution of rutin and quercetin met the DPC's requirements for the SST criteria in TLC identification, and all batches of samples showed good separation of the index components. This method could effectively distinguish Descurainiae Semen from Lepidii Semen. Using modern chromatographic and spectroscopic techniques, the structure of the chromatographic peak adjacent to the component of the index (quercetin-3-O-β- D-glucoside-7-O-β-D-gentiobioside) was identified as descuraic anhydride B. The resolution between the two components in all batches of samples was greater than 3.1, which met the DPC's requirements for the SST criteria in content determination. The results of the methodological investigations met the requirements for content determination. The content of quercetin-3-O-β- D-glucose-7-O-β-D-gentiobioside in 30 batches of samples ranged from 0.062%-0.125%.Conclusion:The established quality standard system for Descurainiae Semen in this article is comprehensive, and meets the requirements of the DPC, which can be used for the quality control of Descurainiae Semen.

BACKGROUND:Macrophages exhibit distinct pro-inflammatory and anti-inflammatory phenotypes.Through tissue engineering techniques,their phenotype transition has made them one of the most studied immune cells in bone injury repair.Recent studies have found that neutrophils also play a significant role in bone injury repair processes,but there is currently no such review available.OBJECTIVE:To summarize the current role of neutrophils in fracture healing and interventions targeting neutrophils to promote fracture healing.METHODS:We searched the Web of Science,PubMed,WanFang Data,and CNKI databases from January 2000 to February 2024 with the key words of"neutrophil,fracture healing,bone damage,bone repair,bone remodeling"in Chinese and English.Literature screening was conducted based on inclusion and exclusion criteria,resulting in a final selection of 72 articles for review.RESULTS AND CONCLUSION:(1)The history of neutrophils has been long,with their importance initially overlooked due to a lack of staining techniques.In 1900,Paul Ehrlich's invention of triacid staining distinguished neutrophils,marking the beginning of research in this field.(2)Under normal conditions,neutrophils migrate to various organs to assist in their physiological functions.In pathological states,neutrophils exert their antimicrobial effects through phagocytosis,degranulation,and the formation of neutrophil extracellular traps.(3)Neutrophils primarily participate in the early hematoma inflammation stage of fracture healing by releasing cytokines to recruit other immune cells and mesenchymal stem cells.They also produce fibrinogen to promote hematoma formation and establish a local microenvironment.(4)Neutrophils transform into two distinct subtypes,N1 and N2,at different stages of fracture healing,coordinating with each other to promote bone repair.(5)Neutrophils recruited to the fracture site participate in the healing process by secreting cytokines such as tumor necrosis factor-alpha,interleukin-6,interleukin-10,fibroblast growth factor-2,monocyte chemoattractant protein-1,and platelet-derived growth factor.(6)Neutrophils regulate osteogenesis/osteolysis balance through interactions with the main cellular components involved in different stages of fracture healing.(7)Similar to the widespread research and application of tissue engineering techniques in modulating macrophage polarization in fracture healing,interventions targeting neutrophils to promote fracture healing hold promising prospects for the future.

Objective:To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China.Methods:A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described.Results:The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age ( P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area ( P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions:The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective:To explore the clinical efficacy of targeted interventional embolization therapy by a multidisciplinary team for the hemorrhagic shock caused by acute pelvic fracture or/and acetabular fracture.Methods:A retrospective study was conducted to analyze the data of 63 patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture who had been admitted to Department of Orthopaedics, The Second Hospital of Shanxi Medical University from January 2015 to July 2022. There were 44 males and 19 females with an age of (39.6±15.6) years, and 23 pelvic fractures, 35 acetabular fractures, and 5 pelvic and acetabular fractures. The time from injury to targeted interventional embolization therapy was 2.67 (2.00, 3.33) hours. All the patients were treated with targeted interventional embolization therapy by a multidisciplinary team involving orthopedics, interventional medicine, general surgery, and urology. The shock index and lactate level within 12 hours after therapy, 24-hour urine output, and incidence of complications 3 weeks after therapy were recorded.Results:No bleeding was found again in the 63 patients after embolization. Within 12 hours after therapy, the shock index was ≤1.0, indicating the shock was corrected. Within 12 hours after targeted interventional embolization therapy, the shock index (0.70±0.46) and lactate value [(2.03±1.35) mmol/L] in the 63 patients were significantly lower than those before therapy [(1.76±0.56) and (4.53±1.74) mmol/L] ( P<0.05). The 24-hour urine output [(50.26±20.38) mL/h] was significantly higher than that before therapy [(21.56±1.27) mL/h] ( P<0.05). Two patients experienced poor blood circulation in the distal skin of the great toe, which was relieved after treatment with blood circulation promotion and anticoagulation. Three patients developed necrosis of the hip soft tissue, which was cured after multiple times of debridement and anti-infection treatments. One patient with severe injury died from multiple organ dysfunction. Conclusions:The targeted interventional embolization therapy can not only diagnose the bleeding location in patients with hemorrhagic shock caused by pelvic fracture or/and acetabular fracture, but also timely and accurately carry out hemostatic treatment to correct shock. Moreover, a multidisciplinary team can help patients avoid multiple surgeries and decrease their pain and financial loss.

Objective To explore the rules of acupoint selection and manipulation application of Tuina in the treatment of diabetes peripheral neuropathy(DPN)with data mining technology.Methods The clinical research literature of Tuina for DPN from October 2022 was selected by searching four Chinese databases that CNKI,WanFang,VIP and Chinese Biomedical Literature Database.Using the traditional Chinese medicine inheritance assistance platform software,analyze and summarize the rules of selecting acupoints and applying manipulations in the treatment of DPN with Tuina.Results A total of 110 articles were included,including 65 acupoints and 33 manipulations.The acupoints with the highest frequency are Zusanli(ST 36),Sanyinjiao(SP 6),Taixi(KI 3),Yongquan(KI 1),Taichong(LR 3),Yanglingquan(GB 34),etc.The meridians mainly include Taiyin Spleen Meridian of Foot,Yangming Stomach Meridian of Foot,Taiyang Bladder Meridian of Foot and Shaoyin Kidney Meridian of Foot.Five-shu Points,Lower He-sea Points and Yuan-primary Points are commonly used specific points.The acupoints are mostly distributed in the lower limbs.The categories of Tuina manipulations mainly include squeezing-pressing manipulations,pushing rolling manipulations and composite manipulations.The Tuina manipulations mainly include kneading manipulation,pressing manipulation,point-pressing manipulation,pressing-kneading manipulation and twisting manipulation with both palms.Conclusion The acupoint selection and manipulation application of Tuina in treating DPN have certain rules,and the main treatment principles are to regulate the organs and dredge collaterals,and to replenish qi and promote blood circulation,which can provide objective basis for clinical treatment.