ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

OBJECTIVE: To evaluate the analgesic efficacy of ultrasound-guided high fascia iliaca compartment block (HFICB) in managing tourniquet-related pain following total knee arthroplasty (TKA). METHODS: A prospective randomized controlled trial was conducted involving 84 patients with severe knee osteoarthritis or rheumatoid arthritis who underwent unilateral TKA between March 2024 and December 2024. Patients were randomly assigned to two groups ( n=42) using a random number table. In the trial group, ultrasound-guided HFICB was performed preoperatively, with 0.2% ropivacaine injected into the fascia iliaca compartment. No intervention was administered in the control group. Baseline characteristics, including gender, age, surgical side, body mass index, and preoperative visual analogue scale (VAS) scores at rest and during movement, showed no significant difference between the two groups ( P>0.05). In both groups, a tourniquet was applied after osteotomy and before pulsed lavage, and removed after the closure of the first layer of the joint capsule. Postoperative assessments were conducted at 6, 12, 24, and 48 hours, including VAS scores at the tourniquet site (at rest and during movement), Bromage motor block scores, Ramsay sedation scores, and Bruggrmann comfort scale (BCS) scores to evaluate patient comfort. Additionally, the average tramadol consumption and incidence of nausea and vomiting within 48 hours postoperatively were recorded and compared. RESULTS: In the trial group and control group, VAS scores during movement at the tourniquet site significantly improved at all postoperative time points compared to preoperative levels ( P<0.05). VAS scores at rest increased transiently at 6 hours after operation in both groups, and then gradually decreased to the preoperative level. Except that there was no significant difference at 48 hours after operation in the trial group ( P>0.05), there were significant differences at other time points of two groups compared to preoperative score ( P<0.05). Except for VAS score at rest at 6 hours, VAS score during movement at 48 hours, and BCS comfort score at 48 hours ( P>0.05), the trial group showed significantly better outcomes than the control group in terms of VAS score at rest, VAS score during movement, Ramsay sedation scores, and BCS comfort scores at all other time points ( P<0.05). No significant difference was found in Bromage motor block scores between the groups ( P>0.05). Tramadol was used in 3 patients in the trial group and 7 patients in the control group within 48 hours after operation, the dosage was (133.30±14.19) mg and (172.40±22.29) mg, showing significant difference ( P<0.05). Nausea and vomiting occurred in 4 patients (9.5%) in the trial group and 3 patients (7.1%) in the control group, with no significant difference in incidence between groups ( P>0.05). CONCLUSION Ultrasound-guided HFICB provides effective analgesia for tourniquet-related pain following TKA, facilitates early postoperative functional recovery of the knee joint, and may serve as a valuable clinical option for postoperative pain management in TKA patients.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Nerve Block/methods* ; Male ; Female ; Pain, Postoperative/etiology* ; Tourniquets/adverse effects* ; Prospective Studies ; Middle Aged ; Ropivacaine/administration & dosage* ; Aged ; Ultrasonography, Interventional ; Anesthetics, Local/administration & dosage* ; Pain Measurement ; Fascia ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Arthritis, Rheumatoid/surgery*

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.

Objective To analyze the correlation between tongue image features and the risk levels of disease in patients with idiopathic membranous nephropathy(IMN).Methods Based on IMN clinical research electronic data acquisition system,a cross-sectional study method was used to analyze the clinical diagnosis and treatment data of 135 IMN patients from Guangdong Provincial Hospital of Chinese Medicine.The patients were grouped according to the risk levels of disease,and then the correlation between the risk levels of disease and tongue image features was analyzed.During the description of tongue image features,TB is for tongue body,TC is for tongue coating,L is for luminance,a is for red-green axis,G is for the value of green,B is for the value of blue,and AUT is for the value of autocorrelation.Results The comparison of tongue image feature indicators of patients with different risk levels of IMN showed that:(1)the higher the level of disease risk of IMN patients,the greater the values of TB-L,TB-G and TB-B(P<0.05 or P<0.01).The values of tongue image indicator TB-a and TC-a of the patients with different risk levels of IMN were shown in decreasing sequence:low-risk group>high-risk group>middle-risk group>extremely-high-risk group(P<0.05).(2)Linear regression analysis showed that TB-L,TB-G,and TB-B were significantly increased in the high-risk group compared with those in the middle-and low-risk groups(P<0.05 or P<0.01),whereas there were no significant differences between the middle-risk group and low-risk group(P>0.05).(3)The results of correlation analysis showed that there was a positive correlation among most of the tongue image feature indicators(including TB-L,TB-G,TB-B,TB-AUT,TC-L,TC-G,and TC-B,etc.)and the risk level of disease,while TB-a was negatively correlated with the risk level of disease,and the differences were all statistically significant(P<0.05 or P<0.01).(4)All patients were treated with Chinese medicine and/or Chinese patent medicine,and 46.7%of patients were given hormones and immunosuppressants,and there was no statistically significant difference in the the use of hormones and immunosuppressants among various groups(P=0.637).Conclusion There is a correlation between the tongue image features of IMN patients and the risk level of disease,and the results will provide an objective reference for the assessment of illness state and traditional Chinese medicine(TCM)syndrome differentiation of IMN patients.With reference to the changes in the tongue image features,the illness state can be precisely identified,which is more accurate than the inspection of four diagnostic methods of TCM.

Objective To evaluate the association of different obesity phenotypes and their components with the risk of cognitive impairment in older Chinese adults,and to assess the association between obesity and cognitive impairment in different cognition-related genetic backgrounds.Methods A cross-sectional study based on the West China Health and Aging Cohort was conducted.Logistic regression was applied to estimate the association of obesity phenotypes and components with cognitive impairment in older Chinese adults stratified by APOE gene and polygenic risk scores.Results A total of 7 316 participants were enrolled,of whom 1 820 had cognitive impairment.Weight gains were associated with a reduced risk of cognitive impairment(odds ratio[OR]=0.96,95%CI,0.95-0.97).Being overweight with a normal waist-to-hip ratio was a protective factor for cognition(OR=0.74,95%CI,0.61-0.90),whereas the coexistence of elevated waist-to-hip ratio and overweight did not increase the risk of cognitive impairment.Sarcopenia was associated with an elevated risk of cognitive impairment.This association was found in both overweight(OR=2.03,95%CI,1.71-2.41)and non-overweight older adults(OR=1.86,95%CI,1.58-2.20),and was significant across all polygenic risk score strata.Conclusion Increasing body mass may serve as a key protective factor against cognitive decline in older adults.Having sarcopenia and obesity is associated with an elevated risk of cognitive impairment,independent of genetic susceptibility.

Background Dibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. Objective To investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. Methods Thirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg⁻¹ DBP exposure group (OVA+DBP), and OVA+40 mg·kg⁻¹ DBP+50 mg·kg⁻¹ 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg⁻¹ DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. Results Compared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P<0.01), the Th2 (IL-4, IL-5, IL-13) and Th17 (IL-17A) cytokines in BALF (P<0.01), and the expression levels of endoplasmic reticulum stress-related proteins IRE1α, PERK and ATF-6 (P<0.01). In addition, after the 4-PBA treatment, it was found that compared with the OVA+DBP group, the expression levels of endoplasmic reticulum stress-related proteins (IRE1α, PERK and ATF-6) were down-regulated in the OVA+DBP+4-PBA group (P<0.01), the levels of cytokines (IL-4, IL-5, IL-13, and IL-17A) in BALF and T-IgE and OVA-IgE in serum were decreased (P<0.01), and airway remodeling and mucous hyperplasia were significantly alleviated. Conclusion Long-term exposure to DBP could aggravate allergic asthma by activating the endoplasmic reticulum stress pathway. This worsening effect is accompanied by the increase of immunoglobulin IgE levels and the release of Th2 and Th17 cytokines, which in turn leads to lung histopathological changes that affect lung function.

AIM:To compare the effects of 0.01% with 0.05% atropine eye drops on pupil diameter(PD)and intraocular pressure(IOP)in myopic children.METHODS: Prospective non-randomized controlled study. A total of 232 myopic children who treated at the Department of Ophthalmology, the Second People's Hospital of Puyang from March 2021 to February 2022 were included. They were divided into 0.01% atropine eye drops group(81 cases), 0.05% atropine eye drops group(77 cases), and control group(74 cases)according to patients' will, respectively. The control group received placebo eye drops(isotonic excipient). The PD and IOP of the three groups of patients were measured before medication and at 6 and 12 mo after medication.RESULTS: Finally, 181 cases(181 eyes)(with all right eye data included in the study)completed a 1-year follow-up, with a loss to follow-up rate of 22.0%(51/232). Among them, 62 cases(62 eyes)belonged to the 0.01% atropine eye drops group, 54 cases(54 eyes)belonged to the 0.05% atropine eye drops group, and 65 cases(65 eyes)belonged to the control group. There was no significant difference in baseline PD and IOP among the three groups(all P<0.05). After 12 mo of medication, the changes in PD among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were 0.79±0.70, 1.29±0.66, and 0.06±0.74 mm, respectively(P<0.001). The change in PD in the 0.05% atropine eye drops group was significantly greater than that in both the 0.01% atropine eye drops group and the control group. Similarly, the change in PD in the 0.01% atropine eye drops group was significantly greater than that in the control group(all P<0.05). After 12 mo of medication, the changes in IOP among the 0.01% atropine eye drops group, 0.05% atropine eye drops group, and control group were -0.70±1.94, -0.22±1.79, and 0.25±2.03 mmHg, respectively(P<0.05). The changes in IOP in the 0.05% atropine eye drops group showed statistically significant difference compared to both the 0.01% atropine eye drops group and the control group(all P>0.05), and the changes in IOP in the 0.01% atropine eye drops group were statistically significant compared to the control group(P<0.05). Multivariate linear regression analysis revealed that baseline refractive error and baseline PD were significant factors influencing the change in PD among children treated with atropine eye drops(β=0.230, 95%CI: 0.005-0.455, SE=0.114, t=2.025, P=0.045; β=-0.562, 95%CI: -0.729--0.396, SE=0.084, t=6.697, P<0.001). Additionally, baseline IOP was significant factor influencing the change in IOP among children in the atropine eye drop groups(β=-0.285, 95%CI: -0.439--0.131, SE=0.078, t=3.662, P<0.001).CONCLUSION: The PD of myopic children increased after using 0.01% and 0.05% atropine eye drops, and the change in PD after using 0.05% atropine eye drops was significantly greater than that of 0.01% atropine eye drops. No risk was found in the use of 0.01% and 0.05% atropine eye drops and elevated IOP.