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 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.

Objective:To study the effects of enoxaparin on osteogenic differentiation of bone marrow stem cells (BMSCs) and the exosomes derived from BMSCs.Methods:After the BMSCs from 4-week old male SD rats were cultured, their surface antigen and multilineage differentiation potentials were identified. Subsequently, the BMSCs were incubated with osteogenic differentiation medium containing 10 IU/mL enoxaparin for 14 days. After the exosomes derived from BMSCs (BMSC-Exos) were extracted by the kit method, their structure was observed by transmission electron microscopy and their surface antigen CD63 detected by Western blot. Alizarin red staining was used to analyze the osteogenic differentiation of BMSCs. Osteogenic proteins including OCN and BMP-2 in BMSCs and exosomes were detected.Results:The spindle-shaped BMSCs isolated and cultured showed a uniform spiral pattern. They expressed highly the surface markers CD29 and CD44 but lowly CD34 and CD45, indicating that the majority of the cells were BMSCs. BMSC-Exos, in an oval shape with a diameter of about 30 to 80 nm, expressed CD63. Alizarin red staining showed that the number of mineralized nodules in the enoxaparin treatment group was significantly lower than that in the control group. Western blot analysis indicated that enoxaparin inhibited the expression of osteocalcin (OCN) and BMP-2 in BMSCs. ELISA results showed that the protein levels of OCN(48.81 ng/mL ± 8.23 ng/mL) and BMP-2 (311.45 pg/mL ± 27.59 pg/mL) in the BMSCs treated with enoxaparin were significantly lower than those of OCN (80.43 ng/mL ± 10.74 ng/mL) and BMP-2 (399.23 pg/mL ± 32.25 pg/mL) in the control BMSCs ( P<0.05). The contents of OCN (1.45 ng/mL±0.15 ng/mL) and BMP-2 (18.47 pg/mL ± 0.54 pg/mL) in the exosomes from BMSCs treated with enoxaparin were significantly higher than those of OCN (1.00 ng/mL ± 0.12 ng/mL) and BMP-2 (9.07 ng/mL ± 0.36 pg/mL) in the exosomes from control BMSCs ( P<0.05). Conclusions:Enoxaparin may inhibit the osteogenic differentiation of BMSCs. The mechanism of this might be related to its direct inhibition against the expression of OCN and BMP-2 in BMSCs and its indirect reduction of OCN and BMP-2 in BMSCs through the exhaust of the above proteins in the form of exosomes.

Objective: To study the value of olfactory cleft scores through computed tomography (CT) in predicting the oral glucocorticoids (GC) sensitivity in chronic rhinosinusitis with nasal polyps. Methods: Fourty-seven consecutive patients with CRSwNP from the Fifth Affiliated Hospital of Sun Yat-sen University between January and March of 2018 were recruited in this prospective, single-blinded study. There were 28 males and 19 females, with age ranging from 17 to 66 years old. After a course of oral prednisone (30 mg/d for 14 d), these patients were subsequently classified into objectively GC-sensitive and -insensitive subgroup according to the change in nasal polyp size score, or subjectively GC-sensitive and -insensitive subgroup according to the change in total nasal symptom score. The following parameters were compared between GC-sensitive and -insensitve subgroups: Lund-Mackay scores, olfactory cleft scores, and blood eosinophil counts and ratio. T test and χ² test were used. Multivariate Logistic regression analysis was used for factor prediction and receiver operating characteristic (ROC) curve was used to analyze the predictive ability of those factors. Results: There were 53.2% (25/47) and 61.7% (29/47) of patients objectively and subjectively sensitive to GC therapy, respectively. All data conformed to normal distribution. The olfactory cleft score and the blood eosinophil counts and ratio in objectively GC-sensitive subgroup were significantly higher than those in objectively GC-insensitive subgroup (3.6±1.0 vs 2.2±1.4, (404.4±200.3)/μl vs (209.5±233.1)/μl, (5.25±2.59)% vs (3.17±3.46)%, t value was 3.98, 3.08, respectively, χ²=2.35, all P<0.05). The cleft score, the blood eosinophil counts and ratio also showed the same trend in subjectively GC-sensitive and -insensitive subgroup (3.6±1.0 vs 1.9±1.3, (401.4±213.6)/μl vs (171.1±200.2)/μl, (5.39±2.76)% vs (2.48±2.99)%, t value was 5.05, 3.68, respectively, χ²=3.40, all P<0.05). Multivariate Logistic regression revealed that olfactory cleft score was an independent risk factor for objective or subjective GC-sensitivity (OR=2.882, 95%CI: 1.301-6.384; OR=2.508, 95%CI: 1.248-5.039). The olfactory cleft score exhibited comparable accuracy with the blood eosinophil ratio as predictor of objective and subjective GC-sensitivity (Area under curve of olfactory cleft score was 0.775, 0.829, respectively). An olfactory cleft score of 3.5 could act as a reliable indicator for predicting the clinical response to GC therapy in CRSwNP. Conclusion Olfactory cleft score through CT scan has the potential value in predicting GC-sensitivity in CRSwNP patients.

Objective To evaluate the clinical and radiologic outcomes of minimally invasive plate percutaneous osteosynthesis (MIPPO) for distal clavicle fractures of Neer type Ⅱ. Methods From May 2015 to May 2016, 13 patients with distal clavicle fracture of Neer type Ⅱwere treated with MIPPO using an anatomic locking plate. Anteroposterior plain X-ray images of the clavicle were taken at intervals until union was observed. Fracture healing time and complications were recorded, and shoulder joint functions evaluated using Constant and University of California at Los Angeles (UCLA) scores. Results The average operating time was 60.9 minutes (range, from 48 to 83 minutes), average intraoperative blood loss 24.7 mL (range, from 18 to 30 mL), and average union time for the patients was 13.3 weeks (range, from 11 to 15 weeks). No delayed union or nonunion occurred. There were no major complications, like infection, plate breakage, or neurovascular injury. Only 2 patients felt local incision numbness. All the patients were satisfactory with their shoulder func-tions. At the final follow-ups, the mean Constant score was 93.2 points (from 87 to 95 points) and the mean UCLA score 30.6 points (from 28 to 34 points). Conclusion In the treatment of distal clavicle fractures of Neer type Ⅱ, minimally invasive plate percutaneous osteosynthesis can not only achieve good clinical and radi-ologic outcomes but also be advantageous over conventional open reduction in aspects of smaller invasion and better cosmetic effect.