OBJECTIVE: To observe the clinical efficacy of combination therapy of wheat-grained sized cone moxibustion and point-to-point needle insertion with medical ozone penetrating injection for allergic rhinitis (AR) and its effect on inflammation-related indexes. METHODS: Thirty-one patients with persistent AR were enrolled. The patients received medical ozone injection at bilateral Yingxiang (LI20)-to-Shangyingxiang (EX-HN8), and wheat-grained sized cone moxibustion at Dazhui (GV14), twice a week (with a 3-day interval) for 4 consecutive weeks. The total nasal symptoms score (TNSS), total non-nasal symptom score (TNNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ), and rhinitis control assessment test (RCAT) scores were evaluated before treatment, after treatment, and at the 8-week follow-up. Levels of eosinophil (EOS) count, immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and IL-17 were measured before and after treatment. Clinical efficacy was evaluated after treatment, and the recurrence rate was assessed at follow-up. RESULTS: Compared with those before treatment, the TNSS, TNNSS, and RQLQ scores were decreased (P<0.05), while the RCAT score was increased (P<0.05) after treatment and at follow-up. There were no statistically significant differences in above indexes between the post-treatment and follow-up (P>0.05). After treatment, the whole blood EOS count and serum levels of IgE, IL-4, IL-6, and IL-17 were decreased compared with those before treatment (P<0.05). After treatment, 17 cases were markedly effective, 12 cases were effective, and 2 cases were ineffective, resulting in a total effective rate of 93.5%. At follow-up, 2 cases relapsed, and the recurrence rate was 6.9%. CONCLUSION Combination therapy of wheat-grained sized cone moxibustion and point-to-point needle insertion with medical ozone injection can improve AR symptoms, reduce the recurrence rate, and enhance the quality of life. The mechanism may be associated with the regulation of immune-related indexes.
Humans ; Female ; Male ; Moxibustion ; Adult ; Ozone/administration & dosage* ; Middle Aged ; Young Adult ; Acupuncture Points ; Adolescent ; Combined Modality Therapy ; Treatment Outcome ; Immunoglobulin E/blood* ; Rhinitis, Allergic/immunology* ; Interleukin-4/immunology*

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health.Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy.This review begins by introducing different types of immune cells in the lung.The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed.The review is expected to provide data for the targeted therapy of infectious pneumonia.

Objective To explore the intrinsic relationship between circadian clock and cell cycle in osteoarthritis(OA)chondrocytes,especially the regulation of cell cycle-related genes by the clock gene Bmal1.Methods The chondroid ATDC5 cells induced by insulin-transfering-selenium(ITS)were divided into control group,OA group and LV-Bmal1 group.The cell viability of each group was detected by CCK8 method.The expression of Bmal1,Per1,Wee1,Cdk1,Ccnb1 and Mmp13 mRNA in each group was detected by RT-qPCR.The expression of BMAL1,PER1,WEE1,CDK1,CCNB1 and MMP13 protein in each group was detected by Western blot.The effects of Bmal1 on different stages of cell cycle and apoptosis was analyzed by flow cytometry.The regulation of Bmal1 on Per1,Wee1,Cdk1,Ccnb1 and Mmp13 and their roles in OA were analyzed.Results Compared with the normal group,the cell viability of the OA group was increased,the relative mRNA expression of Bmal1 and Wee1 in the OA group decreased,and the relative mRNA expression of Per1,Cdk1,Ccnb1 and Mmp13 increased signif-icantly.The cell viability of LV-Bmal1 group decreased,the relative expression of Bmal1 and Wee1 mRNA in-creased,and the relative expression of Per1,Cdk1,Ccnb1 and Mmp13 mRNA decreased(P＜0.05).Correlation analysis showed that Bmal1 was positively correlated with Wee1 and they were negatively correlated with Per1,Cdk1,Ccnb1 or Mmp13.The results of Western blot showed that protein expression in different groups were con-sistent with the trend of PCR.The results of cell cycle and apoptosis showed that compared with the normal group,the S phase and G2/M phase of the OA group were shortened,the proportion of cells decreased significantly,and the proportion of early and late apoptosis increased.The S phase and G2/M phase of the LV-Bmal1 group were prolonged,the proportion of cells was increased,and the proportion of early and late apoptosis was decreased.Conclusions Circadian clock gene Bmal1 in inflammatory chondrocytes might regulate the expression of cell cycle-related genes.

Objective To study the properties and antimicrobial activity of the novel self-assembled antimicrobial peptide(AMP)CR-16,and to provide experimental evidence for the treatment of bacterial infections.Methods CR-16 was designed and synthesized based on the structure of antimicrobial peptides Buforin Ⅱ and LfcinB.Dynamic light scattering(DLS),transmission electron microscopy(TEM),and X-ray diffraction(XRD)were used to characterize CR-16.Based on the results of critical micelle concentration(CMC),the self-assembled properties of CR-16 were investigated using atomic force microscopy(AFM)and circular dichroism(CD).The minimum inhibitory concentration(MIC)was used to study the inhibitory effect of CR-16 while transmission electron microscopy(TEM)was adopted to observe the interactions between CR-16 and the outer membrane of bacteria.Results AMP CR-16 was prepared as self-assemblies,which were regularly spherical in shape and stable in activity.CR-16 could inhibit both the growth of Escherichia coli and,more importantly,the growth of NDM-1-producing carbapenem-resistant Escherichia coli,promising good prospects in treating infections caused by antibiotic-resistant bacteria.Conclusion CR-16 can be self-assembled and deliver antibacterial effects against Escherichia coli.

Objective To enhance the photostability of colchicine(COL)for sustained-release COL pellets.Methods The degradation was investigated by studying the photochemical degradation kinetics of COL.The impact of such physical properties of the photostabilizers as the type,color,dosage,and position on the photostability of COL in sustained-release pellets was also evaluated.Results The contents of photochemical degradation products did not increase after 10 days of light exposure to sustained-release COL pellets with red iron oxide of 4％(w/w)as the protective layer.Conclusion The findings of this study indicate that use of iron oxide as a photostabilizer in sustained-release COL pellets can significantly reduce the photochemical degradation of COL in the pellets.

Objective To develop a deep learning network based on attention mechanism to identify the number of the vertical man-dibular third molar(MTM)roots(single or double)on panoramic radiographs in an automatic way.Methods The sample consisted of 1 045 patients with 1 642 MTMs on paired panoramic radiographs and Cone-beam computed tomography(CBCT)and were randomly grouped into the training(80%),the validation(10%),and the test(10%).The evaluation of CBCT was defined as the ground truth.A deep learning network based on attention mechanism,which was named as RN-MTMnet,was trained to judge if the MTM on pano-ramic radiographs had one or two roots.Diagnostic performance was evaluated by accuracy,sensitivity,specificity,and positive predict value(PPV),and the receiver operating characteristic(ROC)curve with the area under the ROC curve(AUC).Its diagnostic perform-ance was compared with dentists'diagnosis,Faster-RCNN,CenterNet,and SSD using evaluation metrics.Results On CBCT images,single-rooted MTM was observed on 336(20.46%)sides,while two-rooted MTM was 1 306(79.54%).The RN-MTMnet achieved an accuracy of 0.888,a sensitivity of 0.885,a specificity of 0.903,a PPV of 0.976,and the AUC value of 0.90.Conclusion RN-MTM-net is developed as a novel,robust and accurate method for detecting the numberof MTM roots on panoramic radiographs.

Objective:To discusse the influencing factors of lung metastasis in elderly patients (≥60 years old) with clear cell renal cell carcinoma (ccRCC) based on Surveillance, Epidemiology, and End Results (SEER) database, and to construct and evaluate the nomogram prediction model.Methods:The SEER database was used to retrieve the data of elderly ccRCC patients from 2017 to 2021. The screened 8 183 ccRCC patients were randomly assigned to the training set ( n=5 728) and the validation set ( n=2 455) at a ratio of 7∶3 by using the software R4.4.1. The incidence of lung metastasis in elderly patients with ccRCC was calculated, and the influencing factors of lung metastasis in elderly patients with ccRCC were analyzed by univariate and multivariate logistic regression. According to the results of multivariate analysis, the nomogram prediction model was constructed, and the prediction efficiency of the model was evaluated by using the receiver operator characteristic (ROC) curve, the clinical application value of the prediction model was evaluated by calibration curve and decision curve analysis (DCA) . Results:A total of 8 183 elderly ccRCC patients were retrieved, including 620 patients with lung metastasis, and the incidence of lung metastasis was 7.58%. Univariate analysis showed that, race (white race: OR=1.58, 95% CI: 1.01-2.49, P=0.046; others: OR=1.85, 95% CI: 1.10-3.10, P=0.020), sex ( OR=1.32, 95% CI: 1.07-1.64, P=0.009), maximum tumor diameter (55-95 mm: OR=8.22, 95% CI: 6.11-11.07, P<0.001; >95 mm: OR=28.12, 95% CI: 20.81-37.99, P<0.001), T stage (T 2 stage: OR=15.62, 95% CI: 11.51-21.19, P<0.001; T 3 stage: OR=7.93, 95% CI: 6.06-10.36, P<0.001; T 4 stage: OR=28.65, 95% CI: 18.71-43.86, P<0.001), N stage ( OR=17.18, 95% CI: 13.36-22.10, P<0.001) and surgery situation ( OR=0.12, 95% CI: 0.09-0.14, P<0.001) were all influencing factors for lung metastasis in elderly patients with ccRCC. Multivariate analysis showed that, race (white race: OR=1.82, 95% CI: 1.07-3.09, P=0.027; others: OR=2.18, 95% CI: 1.17-4.05, P=0.014), maximum tumor diameter (55-95 mm, OR=4.63, 95% CI: 3.13-6.86, P<0.001; >95 mm, OR=8.29, 95% CI: 5.28-13.02, P<0.001), T stage (T 2 stage: OR=2.26, 95% CI: 1.45-3.51, P<0.001; T 3 stage: OR=3.38, 95% CI: 2.28-5.01, P<0.001; T 4 stage: OR=2.45, 95% CI: 1.39-4.31, P=0.002), N stage ( OR=3.81, 95% CI: 2.81-5.17, P<0.001) and surgery situation ( OR=0.10, 95% CI: 0.08-0.14, P<0.001) were independent influencing factors of lung metastasis in elderly patients with ccRCC. According to the results of multivariate analysis, a nomogram prediction model was constructed based on race, maximum tumor diameter, T stage, N stage and surgery situation. ROC curve analysis showed that the area under the curve (AUC) of the prediction model in the training set and the validation set for predicting lung metastasis in ccRCC patients was 0.91 (95% CI: 0.90-0.92) and 0.91 (95% CI: 0.89-0.93), respectively, which indicated that the prediction model had excellent distinguishing ability. Calibration curve showed that the actual occurrence probability of the training set and the validation set was consistent with the predicted probability, which showed that the calibration degree of the prediction model was good. DCA curve showed that the predictive model had good discrimination ability in both training set and validation set, which indicated that the predictive model had potential clinical application value. Conclusion:The incidence of lung metastasis in elderly patients with ccRCC is high. Race, maximum tumor diameter, T stage, N stage and surgery situation are all independent influencing factors of lung metastasis in elderly patients with ccRCC. The prediction model based on the above indexes has excellent prediction efficiency and clinical application value, and can be used to predict the risk of lung metastasis in elderly patients with ccRCC.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the iodine nutritional level of residents in iodine adequate areas in Henan Province, and provide basis for making policy of targeted guidance and rational iodine supplementation.Methods:In the 156 counties of Henan Province in 2020, one township was selected from each location (east, west, south, north and middle) in each county; one school was selected from each township; 40 children aged 8-10 years in the school and 20 pregnant women in the township were selected to collect their urine and salt samples to test urine and salt iodine levels. One third of the counties were selected to examine the thyroid gland of children. Individuals lived in villages with water iodine between 40 and 100 μg/L were included in the study.Results:In iodine adequate areas, a total of 2 097 salt samples were collected from children and tested, the consumption rate of qualified iodized salt was 93.6% (1 962/2 097). A total of 2 096 urine samples were collected from children and tested, and the median urinary iodine was 288.0 μg/L. The goiter rate of children was 0.7% (5/723). A total of 1 068 salt samples from pregnant women were tested, and the consumption rate of qualified iodized salt was 93.0% (993/1 068). A total of 1 068 urine samples from pregnant women were tested, with a median urinary iodine 232.7 μg/L. Stratified by water iodine (40-59, 60-79, 80-100 μg/L), the median urinary iodine of children was 273.8, 288.6, and 305.9 μg/L, respectively, statistically significantly different between groups ( H = 15.79, P < 0.001); the goiter rate of children was ≤2%, and the difference between groups was statistically significant (χ 2 = 7.31, P = 0.026); but the median urinary iodine of pregnant women was not significantly different ( H = 1.82, P = 0.402). Under different water iodine conditions, there was no significant difference in urinary iodine levels in children and pregnant women between the high salt iodine concentration group (≥21 mg/kg) and the low salt iodine concentration group (< 21 mg/kg, P > 0.05). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is relatively high, and the iodine nutrition of pregnant women is appropriate. The goiter rate of children is at a relatively low level. Continuous surveillance should be conducted to comprehensively evaluate the iodine nutrition level. Various measures will be taken by regions and populations.