Background Industrial emissions are a well-established major source of urban fine particulate matter (PM_2.5) and associated heavy metals. To improve local air quality, Shanghai No. 1 Iron and Steel Plant in Baoshan District was entirely relocated, with all production lines successively shut down in 2018. Objective To evaluate the trends in PM_2.5 and three heavy metal concentrations - chromium (Cr), mercury (Hg), and thallium (Tl) —in the local atmosphere pre- and post- relocation of the steel plant. Methods Taking the steel plant relocation in 2019 as the intervention cutoff point, this study was divided into two phases: pre-intervention (January 2017 to December 2018) and post-intervention (January 2019 to December 2021). Monthly mean pollutant concentrations were used to construct an interrupted time series (ITS) model, followed by segmented linear regression to assess the pre- and post-intervention trends in ambient PM_2.5 and three heavy metals surrounding thesteel plant. Results The ITS regression analysis revealed that the change in PM_2.5 concentration (b₂) after the intervention was −7.16 μg·m⁻³, while the changes in Cr, Hg, and Tl concentrations (b₂) were −0.46, −0.03, and −0.06 ng·m⁻³, respectively. Prior to the intervention, PM_2.5 mass concentrations exhibited a temporal decline with a slope of b₁ = –0.69 (P<0.05); seasonal adjustment further strengthened the overall significance of the model. Before the intervention, the concentration of Cr increased over time, with a slope of b₁=0.12 (P<0.05). After the intervention, the concentration of Cr showed a gradual downward trend over time, with a slope (b₁ + b₃) of −0.04, and significant seasonal variations were observed. The concentration of Hg decreased over time before the intervention, with a slope of b₁=−0.0029 (P<0.05). After the intervention, the slope was −0.0003, showing a further slow decline in Hg concentration over time. However, no significant seasonal trend was observed for Hg. The mass concentration of Tl decreased after the intervention, and the difference before and after the intervention was statistically significant (P<0.05). PM_2.5, Cr, and Tl better fit to the seasonal model, whereas Hg showed a better fit to the non-seasonal model. Conclusion The steel plant relocation intervention has markedly improved local air quality.

To summarize the experience of Professor WANG Qingguo in diagnosing and treating wind-cold-dampness arthralgia based on the principle that "the nutrient-defense qi does not merge with wind-cold-dampness qi， so it did not result to arthralgia". By analyzing the relationship between nutrient-defense qi and wind-cold-dampness arthralgia， it is believed that the occurrence of wind-cold-dampness arthralgia is closely related to the movement of nutrient qi and defense qi， and the key to the treatment of this disease is to regulate nutrient qi and defense qi and remove the combination of nutrient-defense qi and wind-cold-dampness qi. The core pathogenesis of wind-cold-dampness arthralgia in the early stage is the initial combination of nutrient-defense qi and wind-cold-dampness qi， and the treatment should harmonize nutrient-defense qi and eliminate the pathogen and release pathogenesis， with Chaihu Guizhi Decoction （柴胡桂枝汤） as the main prescription； the core pathogenesis of the middle stage is nutrient-defense qi and wind-cold-dampness qi cemented together， and the treatment should harmonize and tonify nutrient qi and defense qi and separate the pathogen to alleviate disease， with self-prescribed Chuanteng Tongbi Decoction （穿藤通痹汤） as the main prescription； the core pathogenesis of the late stage is deficiency and stagnation of nutrient-defense qi， wind-cold-dampness qi still exist， and the treatment should tonify and free nutrient qi and defense qi to eliminate pathogen and arthralgia， with self-prescribed Chuanqing Haijia Decoction （穿青海甲汤） plus Duhuo Jisheng Decoction （独活寄生汤） as the main prescription.

Objective:To compare the imaging quality and metabolic quantitative parameters of pulmonary nodules between Q. Flex whole information five-dimensional (5D) and conventional three-dimensional (3D) PET/CT imaging for clinical evaluation.Methods:Fifty-four patients (30 males, 24 females, age: 60(42, 75) years; 78 solid pulmonary nodules (maximum diameter≤3 cm) with abnormal uptake of 18F-FDG) from Tianjin Cancer Hospital Airport Hospital between June 2022 and August 2022 were enrolled in this retrospective study. All patients underwent 5D scanning and 3D, 5D reconstruction. Image quality scores, signal-to-noise ratio (SNR), SUV max, SUV mean and metabolic tumor volume (MTV) of pulmonary nodules of 5D group and 3D group were evaluated and compared with χ2 test and Wilcoxon signed rank test. Correlation of quantitative parameters between 2 groups were analyzed by using Spearman rank correlation analysis. Results:Thirty-five of 78(45%) pulmonary nodules with image quality score≥4 were found in 5D group, which were more than those in 3D group (22/78(28%); χ2=4.67, P=0.031). Meanwhile, SNR, SUV max, SUV mean, and MTV were significantly positively correlated between the 2 groups ( rs values: 0.86, 0.86, 0.85, and 0.95, all P<0.001). SNR, SUV max and SUV mean of pulmonary nodules in 5D group were significantly higher than those in 3D group, which were 37.46(18.42, 62.00) vs 32.72(16.97, 54.76) ( z=-4.07, P<0.001), 9.71(5.48, 13.82) vs 8.96(4.82, 12.63) ( z=-3.05, P<0.001) and 6.30(3.39, 8.94) vs 5.61(2.99, 7.63)( z=-4.07, P<0.001) respectively. MTV of pulmonary nodules in 5D group was significantly lower than that in 3D group, which was 1.72(0.66, 2.74) cm 3vs 1.98(1.06, 4.63) cm 3 ( z=-7.13, P<0.001). Quantitative parameters of lower lung field and nodules with maximum diameters of >10 mm and ≤20 mm based on 5D scanning changed most significantly compared with those based on 3D scanning ( z values: from -5.23 to -2.48, all P<0.05). Conclusion:Q. Flex 5D PET significantly improves the quantitative accuracy of SUV and MTV of pulmonary nodules, and the improvement of image quality is substantial without increasing the radiation dose, which has clinical practical value.

AIM To investigate the effects of Moluodan Dami Pills on chronic atrophic gastritis(CAG)rats and their mechanism.METHODS The rat models were randomly divided into the model group,the low-dose group and high-dose Moluodan Dami Pills groups(2.43 g/kg and 4.86 g/kg),and vitamin A group(0.32 g/kg),following the 16 weeks successful induction of CAG by five-factor modeling method,in contrast to another 10 normal rats of the control group.After 8 weeks corresponding administration,the rats of each group had their general physiological status and pH value of gastric juice assessed;their pathological changes of gastric mucosa observed by naked eyes combined with HE staining;their changes of gastrin-secreting cells(G cells)and somatostatin-secreting cells(D cells)in gastric mucosa observed by immunohistochemistry;and their serum levels of pepsinogen Ⅰ/pepsinogen Ⅱ(PG Ⅰ/PG Ⅱ)ratio,TNF-α and IL-6 detected by ELISA.RESULTS Compared with the model group,the groups intervened with Moluodan Damei Pills and vitamin A displayed lower pH values of gastric juice(P＜0.05),improved pathological changes of gastric mucosa,increased G and D cells counts(P＜0.05,P＜0.01),increased ratio of serum PGⅠ/PGⅡ,and decreased levels of IL-6 and TNF-α(P＜0.05,P＜0.01).CONCLUSION Moluodan Dami Pills can effectively improve the symptoms of CAG rats through its influence on the number and secretion abilityof G and D cells,the levels of serum PG Ⅰ/PG Ⅱ ratio and inflammatory factors.

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; B7-H1 Antigen/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Tomography, X-Ray Computed ; Immunotherapy

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ²=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.
Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adult ; Aged ; Nasal Polyps/drug therapy* ; Omalizumab/therapeutic use* ; Rhinitis/drug therapy* ; Retrospective Studies ; Asthma/diagnosis* ; Rhinitis, Allergic/drug therapy* ; Sinusitis/drug therapy* ; Antibodies, Monoclonal/therapeutic use* ; Chronic Disease

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective: To investigate the application and clinical efficacy of ultrasound debridement method in residual burn wounds. Methods: A retrospective cohort study was conducted. From August 2017 to August 2021, 64 patients with residual burn wounds who met the inclusion criteria were admitted to the 980^th Hospital of the Joint Logistic Support Force of PLA. According to the debridement method adopted for the residual wounds, the patients were divided into ultrasound debridement group (34 cases, 22 males and 12 females, aged (31±13) years) and traditional debridement group (30 cases, 19 males and 11 females, aged (32±13) years). After the corresponding debridement, the wounds of patients in the two groups were selected for stamp skin grafting or large skin grafting according to the wound site and skin donor status. For unhealed wounds after stage Ⅰ surgery, secondary debridement and skin grafting were be performed, with the wound debridement methods in the 2 groups being the same as those of stage Ⅰ, respectively. On postoperative day 3, drug-sensitive test was used to detect the bacteria in the wound and the positive rate of bacteria was calculate. On postoperative day 7, the survival rate of skin slices in wound and the incidence of subcutaneous hematoma were calculated. At discharge, wound healing time and debridement times of patients were counted, and the secondary debridement rate was calculated. Data were statistically analyzed with independent sample t test or chi-square test. Results: On postoperative day 3, the wounds in ultrasound debridement group were infected with Staphylococcus aureus in 2 cases and Pseudomonas aeruginosa in 2 cases, and the wounds in traditional debridement group were infected with Staphylococcus aureus in 5 cases, Pseudomonas aeruginosa in 3 cases, Acinetobacter baumannii in 1 cases, Klebsiella pneumoniae in 1 cases, and Enterobacter cloacae in 1 cases. The positive rate of bacteria of wound in ultrasound debridement group was significantly lower than that in traditional debridement group (χ²=5.51, P<0.05). On postoperative day 7, the survival rate of skin grafts in ultrasound debridement group was (92±5) %, which was significantly higher than (84±10) % in traditional debridement group (χ²=6.78, P<0.01); the incidence of subcutaneous hematoma in ultrasound debridement group was 17.6% (6/34), which was significantly lower than 40.0%( 12/30) in traditional debridement group, χ²=3.94, P<0.05. At discharge, the wound healing time in ultrasound debridement group was (11.0±2.0) d, which was significantly shorter than (13.0±3.1) d in traditional debridement group (t=3.81, P<0.01); the secondary debridement rate of wounds in ultrasound debridement group was 2.9% (1/34), which was significantly lower than 20.0% (6/30) in traditional debridement group (χ²=4.76, P<0.05). Conclusions: Ultrasound debridement method can significantly reduce the bacterial load of residual burn wounds, reduce postoperative hematoma formation, and promote the survival of skin grafts to shorten the course of disease of patients.
Male ; Female ; Humans ; Debridement/methods* ; Retrospective Studies ; Treatment Outcome ; Bacteria ; Burns/microbiology* ; Hematoma