1.Exploration on Mechanism of Topical Treatment of Allergic Contact Dermatitis in Mice with Portulacae Herba Based on Nrf2/HO-1/NF-κB Signaling Pathway
Xiaoxue WANG ; Guanwei FAN ; Xiang PU ; Zhongzhao ZHANG ; Xia CHEN ; Ying TANG ; Nana WU ; Jiangli LUO ; Xiangyan KONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):115-123
ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis (ACD) mice with Portulacae Herba based on the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/nuclear factor-κB (NF-κB) signaling pathway. MethodsA total of 70 6-week-old specific pathogen free (SPF) female Kunming mice were adaptively fed for 1 week and randomly divided into blank group, model group, compound dexamethasone acetate cream group (2.075×10-2 g·g-1), blank matrix cream group, low-dose Portulacae Herba cream group (0.1 g·g-1), high-dose Portulacae Herba cream group (0.2 g·g-1), and Portulacae Herba + inhibitor group (0.2 g·g-1 + 30 mg·kg-1 ML385), with 10 mice in each group. One day before the experiment, the mice were shaved on the neck and back. Except for the blank group, the mice in the other groups were treated with 2,4-dinitrochlorobenzene (DNCB) to establish an ACD model. After respective administration, the skin lesion of the mice was scored, and the histopathological changes of the skin were stained with hematoxylin-eosin (HE). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), reactive oxygen species (ROS), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry (IHC), Western blot, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, the mice in the model group had an increased skin lesion score (P<0.01), severe pathological damage to skin tissue, increased content of IL-1β, IL-6, ROS, and MDA in their serum (P<0.01), and decreased content of SOD (P<0.01). In addition, the mRNA and protein expression levels of Nrf2, HO-1, and nuclear factor-κB inhibitor α (IκBα) in skin tissue were up-regulated (P<0.01), while the protein expression levels of phosphorylated (p)-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated (P<0.01). Compared with the model group and the blank matrix cream group, the mice treated with Portulacae Herba had a decreased skin lesion score (P<0.01), reduced pathological damage to skin tissue, decreased content of IL-1β, IL-6, ROS, and MDA in their serum (P<0.01), and increased content of SOD (P<0.01). Additionally, the mRNA and protein expression levels of Nrf2, HO-1, and IκBα in skin tissue were down-regulated (P<0.05,P<0.01), and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated (P<0.05,P<0.01). Compared with the Portulacae Herba + inhibitor group, the high-dose Portulacae Herba cream group had a decreased skin lesion score (P<0.01), alleviated pathological damage to skin tissue, decreased content of IL-1β, IL-6, ROS, and MDA in the serum of mice (P<0.05,P<0.01), and increased content of SOD (P<0.01). The protein expression levels of Nrf2, HO-1, and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated (P<0.05,P<0.01), and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated (P<0.05). ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.
2.Effects of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis mice
Xiaoxue WANG ; Xia CHEN ; Xiang PU ; Guanwei FAN ; Xiangyan KONG ; Ying TANG ; Nana WU ; Jiangli LUO
China Pharmacy 2025;36(11):1352-1357
OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis (ACD) mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared, with the P. oleracea extract solution (1 g/mL, calculated by crude drug) concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group, model group, Mometasone furoate cream group (positive control), blank matrix cream group, P. oleracea low-concentration and high-concentration cream groups. Except for blank group, ACD model was induced in each group using 2,4-dinitrochlorobenzene solution. The blank group and model groups received normal saline, while the remaining groups were treated with their respective creams, once a day, at a dose of approximately 0.5 g per application, continuously for 14 days. At 24 h post-final administration, skin lesions of mice were observed and scored; pathological changes of skin tissue were observed; serum levels of immunoglobulin E(IgE) and tumor necrosis factor-α (TNF-α) were quantified. mRNA expression of MAS-related G protein-coupled receptors (including MrgprA3, MrgprC11, and MrgprD) in dorsal root ganglion (DRG) was assessed; while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group, mice in the model group exhibited severe skin damage, characterized by loss of epidermal architecture, hyperkeratosis of the skin tissue, and the infiltration of a large number of inflammatory cells. The skin injury scores, as well as the serum levels of IgE and TNF-α, and the mRNA expression levels of MrgprA3, MrgprC11, and MrgprD in DRG, were all significantly elevated compared to the blank group (P<0.05 or P<0.01); in contrast, the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced (P<0.05). Compared with model group, mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage, as evidenced by reduced epidermal hyperplasia, mitigated spongiosis in the dermis, and decreased infiltration of inflammatory cells; these quantitative indicators were almost significantly reversed (P<0.05 or P<0.01). No significant differences were observed in the aforementioned skin injuries, pathological alterations, or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice, the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3, MrgprC11 and MrgprD in DRG, and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.
3.Adolescent anxiety and non-suicidal self-injury behavior: the mediating role of depression and the moderating role of social support
Juexi LI ; Liyuan LI ; Yuxuan GUO ; Xiaoqiang XIAO ; Peiqi TANG ; Ting PU ; Haixi ZUO ; Ting YANG ; Xiaoxia FAN ; Bo ZHOU
Sichuan Mental Health 2025;38(4):357-363
BackgroundNon-suicidal self-injury (NSSI) behavior among adolescents has become a global public health concern. Anxiety and depression are considered key factors influencing NSSI behavior, while social support may play a protective role in alleviating emotional and behavioral issues. However, existing research has primarily focused on the direct impact of individual factors on NSSI behavior, with insufficient exploration of the combined effects of anxiety, depression and social support. ObjectiveTo investigate the direct effect of anxiety on NSSI, the mediating role of depression and the moderating role of social support in relationship between anxiety and NSSI behavior, thus to provide references for the prevention and intervention of NSSI behavior among adolescents. MethodsIn February 2022, a total of 40 820 students in grades 7 to 12 across 10 middle schools in a district of Chengdu were selected as participants, and they were assessed using Generalized Anxiety Disorder Scale-7 item (GAD-7), Patient's Health Questionnaire Depression Scale-9 item (PHQ-9), Social Support Scale for Urban Students (SSSUS) and Adolescent Self-Harm Scale (ASHS). Pearson correlation analysis was conducted to examine the correlations between scale scores among adolescents with NSSI behaviors. Mediation and moderation analyses were performed using Process 3.5 in SPSS, and the significance was tested with bootstrapping. The interaction was visualized by using simple slope analysis. ResultsAmong 34 534 (84.60%) valid respondents, 542 adolescents (1.57%) reported engaging in NSSI behavior. Significant differences in gender, GAD-7 scores, PHQ-9 scores, and SSSUS scores were observed between NSSI behavior group and non-NSSI group (χ²/t=62.889, 71.120, 94.365, -41.464, P<0.01).Adolesents with NSSI showed positive correlations between GAD-7 scores and both ASHS and PHQ-9 scores (r=0.158, 0.166, P<0.01). PHQ-9 scores were positively correlated with ASHS scores (r=0.364, P<0.01), but negatively correlated with SSSUS scores (r=-0.290, P<0.01). SSSUS scores were negatively correlated with ASHS scores (r=-0.247, P<0.01). Depression partially mediated the relationship between anxiety and NSSI behavior, with an effect size of 0.544 (95% CI: 0.162~0.944), accounting for 35.79% of the total effect. Social support moderated the relationship between depression and NSSI bahavior, with an effect value of -0.082 (95% CI: -0.135~-0.029). ConclusionAnxiety not only directly influences NSSI bahavior among adolescents, also indirectly exacerbates it through depression, while social support mitigates the impact of depression on NSSI behavior. [Funded by Youth Project of National Natural Science Foundation of China (number, 82401812); Project of Health Commission of Sichuan Province (number, 24LCYJPT18)]
4.Comparison of clinical outcome between the percutaneous pedicle screw fixation and Wiltse approach for the treatment of thoracolumbar fractures without neurological injury
Mengmeng CHEN ; Pu JIA ; Hao CHEN ; Li BAO ; Guan SHI ; Fei FENG ; Shuangjiang ZHANG ; Hai TANG
International Journal of Surgery 2024;51(3):159-165
Objective:To compare the safety and efficacy of two different minimally invasive approaches to implant pedicle screw for the treatment of single-segment thoracolumbar spine fractures without nerve injury.Methods:This was a retrospective study. Eighty patients with mono-segmental thoracolumbar fractures treated with minimally invasive pedicle screw fixation at Beijing Friendship Hospital, Capital Medical University from January 2020 to June 2022 were included. There were 46 males and 36 females, the age was (45.93±7.91) years old, and ranged from 27 to 60 years old. They were divided into two groups according to different surgical techniques: percutaneous pedicle screw fixation group ( n=44) and Wiltse approach group ( n=36). The operative time, operative visible blood loss, hidden blood loss, total blood loss, fluoroscopy times, incision length, hospital time after surgery and ambulation time were compared. Visual analogue scale (VAS), Oswestry disability index (ODI), ratio of the vertebral anterior height, angle of injured vertebral endplate were recorded and compared between two groups before surgery and at 3 days, 6 months and 1 year after surgery. The accuracy of pedicle screw position and the facet joint violation rate were evaluated by using the postoperative CT scan. Perioperative related complications were investigated. Normally distributed numerical data were presented as mean ± standard deviation, and differences between the groups were compared using t-test. The counting data were expressed as percentages or rates and compared using χ2 test. Results:All patients were followed for a minimum of 12 months. There is no significant difference between the two groups in intraoperative visible blood loss, hospital time after surgery, ambulation time, postoperative VAS and ODI, ratio of vertebral anterior height and angle of injured vertebral endplate at 3 days after surgery, pedicle screw position accuracy and perioperative complications ( P>0.05). The operative time, hidden blood loss, total blood loss, intraoperative fluoroscopy times, facet joint violation rate in the percutaneous pedicle screw fixation group were remarkably higher than in the Wiltse approach group ( P<0.05). The ratio of vertebral anterior height in the percutaneous pedicle screw fixation group was dramatically lower than in the Wiltse approach group at 6 months and 1 year after surgery ( P<0.05). The postoperative injured vertebral endplate angle was higher in the percutaneous pedicle screw fixation group than that in the Wiltse approach group at 6 months and 1 year ( P<0.05). Conclusions:Both percutaneous pedicle screw fixation and Wiltse approach were safe and effective minimally invasive surgical procedures for the treatment of thoracolumbar fractures without neurological injury. The Wiltse approach can reduce fluoroscopy times and perioperative hidden blood loss, reduce the risk of facet joint violation, and maintain a better reduction than percutaneous pedicle screw fixation.
5.Biomechanical characteristics of a novel interspinous distraction fusion device BacFuse for the repair of lumbar degenerative disease
Mengmeng CHEN ; Li BAO ; Hao CHEN ; Pu JIA ; Fei FENG ; Guan SHI ; Hai TANG
Chinese Journal of Tissue Engineering Research 2024;28(9):1325-1329
BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.
6.Analysis and research of online teaching supervision based on the characteristics of medical disciplines
Jiamin YANG ; Yang ZOU ; Hongyi HU ; Chuanhai PU ; Wei ZHANG ; Yujin LIU ; Peihan LI ; Yu TANG
Chinese Journal of Medical Education Research 2024;23(2):242-245
Given the systematic, rigorous, and practical characteristics of medical disciplines, ensuring the teaching quality of online courses has become a significant focus. In traditional teaching models, teaching supervision is an important method to guarantee instructional quality, and introducing teaching supervision into online teaching activities is of great significance. This article systematically reviews and summarizes the domestic and international experience of conducting online medical courses. We explore the instructional supervision of online medical courses from the following perspectives: the meaning of supervision, the necessity of online supervision, online supervision methods and technical approaches, the feedback and application of supervision information, and the establishment of a standardized online supervision process.
7.Mid-and long-term efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type of juvenile developmental dysplasia of the hip
Chuan LI ; Dianzhong LUO ; Tang LIU ; Hui CHENG ; Chao SHEN ; Tao YE ; Baochuang QI ; Xuhan MENG ; Zhifang TANG ; Qing Yong XU ; Luqiao PU
Chinese Journal of Orthopaedics 2024;44(6):388-394
Objective:To investigate the mid-and long-term clinical efficacy of modified Colonna arthroplasty in the treatment of unilateral dislocation type developmental dysplasia of hip (DDH) in adolescents.Methods:A total of 28 adolescent DDH patients with unilateral dislocation who underwent modified Colonna capsular arthroplasty from January 2016 to January 2018 in the 920th Hospital of Joint Logistics Support Force of People's Liberation Army were retrospectively analyzed. There were 4 males and 24 females, aged 16.5±5.0 years (range, 10-25 years). The mean body mass index was 21.2±1.1 kg/m 2 (range, 18.7-24.1 kg/m 2). According to DDH classification, 10 cases were Tonnis type III and 18 cases were Tonnis type IV. The postoperative lateral center-edge angle, acetabular coverage, femoral anteversion angle and leg length discrepancy were measured. The operation time, intraoperative blood loss, visual analogue scale (VAS) of hip pain, Harris hip score (HHS) and congenital dislocation of the hip score were recorded. Results:All patients successfully completed the operation and were followed up for 72.1±5.2 months (range, 60-84 months). The operation time was 81.6±4.3 min (range, 70-90 min), the intraoperative blood loss was 177.5±12.6 ml (range, 160-200 ml), and the hospital stay was 6.8±0.7 days (range, 6-9 days). The VAS score of the hip joint was 1.8±0.6 before operation and 2.3±0.6 at the last follow-up, and the difference was not statistically significant ( t=2.845, P=0.224). The preoperative HHS score was 57.1±5.9, and it increased to 87.3±4.0 at the last follow-up, and the difference was statistically significant ( t=-22.141, P=0.001). At the last follow-up, the femoral anteversion angle was 17.0°±1.5°, which was lower than that before operation 41.6°±2.4°, with a statistically significant difference ( t=-44.868, P=0.008). The leg length discrepancy was 10.2±2.3 mm, which was lower than that before operation (26.4±6.1 mm), with a statistically significant difference ( t=-12.892, P<0.001). The lateral center-edge angle was 28° (26°, 30°), and the acetabular coverage rate was 78% (76%, 79%). The curative effect evaluation standard score of congenital dislocation of the hip was 24 (16.7, 25.7) points, including 7 excellent cases, 14 good cases, 4 fair cases, and 3 poor cases. The excellent and good rate was 75% (21/28). Conclusion:The modified Colonna arthroplasty for the treatment of unilateral dislocation DDH in adolescents has good mid-and long-term hip function recovery and radiographic improvement.
8.Preliminary biomechanical analysis and histological evaluation of fusion capacity after the implantation of interspinous distraction fusion device
Li BAO ; Mengmeng CHEN ; Hao CHEN ; Pu JIA ; Fei FENG ; Guan SHI ; Hai TANG
International Journal of Surgery 2024;51(7):476-481
Objective:To explore interspinous fusion capacity after interspinous distraction fusion (ISDF) device implantation, a preliminary biomechanical analysis and histological evaluation were performed.Methods:The experimental animals were procured from the Science and Research Laboratory Animal Center of Beijing Friendship Hospital, Capital Medical University. The animals were 8-9 weeks old and with an average weight of 25 kg. 15 mini-pigs were randomly divided into three groups, the sham operation group, the decompression group and the ISDF fixed decompression group, 5 animals per group. The sham operation group was treated with simple incision and exposed lamina suture. The decompression group received unilateral decompression and the ISDF fixed decompression group experienced unilateral hemilaminectomy decompression and ISDF fixation. The graft-bed site was filled with purified bone graft material without any autograft bone. After 6 months feeding, all experimental animals were sacrificed and the corresponding lumbar vertebrae was obtained. The samples were fixed on the spinal test system and the range of motion of flexion-extension, lateral bending and rotation were tested through a multiaxial robotic system. The ISDF device samples were embedded for hard tissue sections and stained with hematoxylin-eosin and toluidine blue to assess new bone formation. Normally distributed measurement data were expressed as mean±standard deviation( ± s), and independent samples t-test were used for comparisons between groups. Results:In comparison to the sham operation group, the decompression group exhibited a statistically significant increase in intervertebral mobility, with an average of 61.6% in anterior flexion, 44.7% in posterior extension, 65.0% in left lateral flexion, 49.6% in right lateral flexion, 83.8% in left rotation, and 64.2% in right rotation ( P<0.05). In comparison to the decompression group, the ISDF fixed decompression group exhibited a statistically significant decrease in intervertebral mobility, with an average of 40.0% in anterior flexion, 21.3% in posterior extension, 31.7% in left lateral flexion, 22.3% in right lateral flexion, 28.7% in left rotation, and 35.3% in right rotation ( P<0.05). Well-defined bone tissue can be observed in the histological images of ISDF fixed decompression group samples after 6 months. In the histological part, toluidine blue staining showed extensive new bone formation. The hyperchromatic osteoblasts cells and density bone tissue can be observed in hematoxylin-eosin staining slides. Conclusions:The implantation of ISDF provide the necessary stabilization for promoting fusion. The osteogenesis that occurs within graft-bed site of the ISDF device offers the possibility of interspinous fusion.
9.Meta analysis of effects of healthy eating patterns on mortality,ESKD and CVD incidence in patients with CKD
Yang LI ; Hongmei PENG ; Xia HUANG ; Shi PU ; Xiangchun TANG ; Yu SHI
Chongqing Medicine 2024;53(2):264-269
Objective To investigate the impact of healthy eating patterns on the mortality rate and in-cidence rates of end-stage kidney disease(ESKD)and cardiovascular disease(CVD)in the patients with chronic kidney disease(CKD)by meta analysis.Methods The studies on the relationship between the dietary patterns on the mortality,and the incidence rates of ESKD and CVD in the patients with CKD were retrieved from PubMed,Embase,Cochrane Library,CNKI,Wanfang Database and VIP Database.The retrieval time was from the database establishment to January 2023.The two researchers independently screened the literatures,ex-tracted the data and conducted the literature quality evaluation.The RevMan5.3 software was used for the meta-analysis of the included literatures.Results A total of 10 studies were included in this study,involving 27 291 patients.The results showed that the mortality(HR=0.70,95%CI:0.57-0.87,Z=3.18,P=0.001)and the ESKD incidence rate(HR=0.80,95%CI:0.71-0.91,Z=3.44,P<0.001)and CVD inci-dence rate(HR=0.77;95%CI:0.61-0.97,Z=2.21,P=0.003)had statistical differences between the pa-tients with high dietary score and the patients with low dietary score.Conclusion Persisting in the healthy dieta-ry patterns could decrease the mortality rate,and incidence rates of ESKD and CVD in the patients with CKD.
10.Research progress on the role of miRNA in drug resistance of pleural mesothelioma
Xinmeng WANG ; Jinsong LI ; Yaru LIN ; Ximin TANG ; Yuanqian PU ; Jiaji ZI ; Wei XIONG
China Pharmacy 2024;35(22):2832-2836
Pleural mesothelioma (PM) is a rare malignant tumor originating from the pleura. Most patients are already in the advanced stage at the time of diagnosis, resulting in a low overall survival rate. MicroRNA (miRNA), as key regulators of tumor epigenetic modification, have an intertwined interactive network with PM drug resistance. The mechanisms of drug resistance in PM to chemotherapeutic drugs include increasing drug efflux, reducing drug intake, enhancing DNA repair, and altering drug targets. The mechanisms of resistance to targeted therapy drugs include activating alternative signaling pathways, establishing a favorable tumor microenvironment, and triggering epithelial-mesenchymal transition. MiRNA plays a key part in the aforementioned resistance mechanisms, with some miRNAs promoting the drug sensitivity of cancer cells, while others contribute to increased drug resistance. In light of these key regulatory functions, targeting the dysregulated expression of endogenous miRNAs in the process of resistance formation using miRNA antagonists or miRNA mimics may be an effective therapeutic strategy to reverse drug resistance in PM.

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