1.Successful treatment of extracorporeal membrane oxygenation bridging to lung transplantation in a patient with rapidly progressive interstitial lung disease
Yi GONG ; Xinyu LING ; Rui YAN ; Bo SUN ; Ke MA ; Guifang WANG ; Chang CHEN
Chinese Journal of Clinical Medicine 2026;33(1):154-159
A 42-year-old male with chest tightness and dyspnea was admitted to the hospital. Chest CT indicated diffuse interstitial lung infiltration. Despite receiving anti-infective therapy, glucocorticoid therapy, and immunosuppressive agents, the patient developed refractory hypoxaemia. Endotracheal intubation and invasive mechanical ventilation failed to improve oxygenation. Therefore the patient was diagnosed with rapidly progressive interstitial lung disease (RP-ILD) accompanied by type Ⅰ respiratory failure. Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) was initiated, and oxygenation improved in this patient. The patient subsequently underwent bilateral lung transplantation with veno-arterio-venous (VAV) ECMO support. ECMO machine was withdrawn on day 1, and extubation was achieved on day 9 after surgery. Histopathology revealed fibrotic nonspecific interstitial pneumonia (NSIP) with hyaline membrane formation. The patient developed ICU-acquired myasthenia and received early rehabilitation, with gradual recovery of muscle strength. During follow-up, graft lung function remained stable. This case demonstrates that ECMO can serve as a bridge to lung transplantation in RP-ILD patients.
2.Clinical observation of radiofrequency minimally invasive treatment for conjunctivochalasis-induced epiphora
Xuan ZHENG ; Xiaozhao YANG ; Hua YANG ; Yi ZHANG ; Bo WANG
International Eye Science 2026;26(3):528-533
AIM: To evaluate the surgical outcomes and changes in the ocular surface microenvironment following radiofrequency minimally invasive treatment for conjunctivochalasis-induced epiphora.METHODS: Patients with epiphora primarily caused by conjunctivochalasis were enrolled. All patients had conjunctivochalasis of ≥grade II, and their symptoms showed no significant improvement after previous pharmacological treatment. All patients underwent radiofrequency minimally invasive correction of conjunctivochalasis, supplemented with artificial tears, anti-inflammatory therapy, and ocular surface repair treatment postoperatively. At 8 wk post-surgery, the ocular surface disease index(OSDI), eye redness, tear secretion, non-invasive tear break-up time, lipid layer thickness, tear ferning test, and conjunctival impression cytology were assessed to compare treatment efficacy and observe changes in the ocular surface microenvironment.RESULTS: A total of 43 cases(43 eyes)of conjunctivochalasis and with a main complaint of epiphora were included, including 23 males and 20 males, with a mean age of 64.69±3.36 years. The total effective rate of surgery was 91% at 8 wk postoperatively. Compared with preoperative values, the OSDI scores significantly decreased and the non-invasive tear break-up time was prolonged at 8 wk post-surgery(all P<0.05). No statistically significant differences were observed in lipid layer thickness or tear secretion at 8 wk postoperatively(all P>0.05). The normal rate of chloramphenicol taste test increased from 21% preoperatively to 63% postoperatively; the normal rate of eye redness increased from 40% to 70%; normal rate of tear ferning grading improved from 30% to 63%; and normal conjunctival impression cytology grading increased from 21% to 74%.CONCLUSION: Radiofrequency minimally invasive treatment is effective for conjunctivochalasis and is straightforward to perform. Patients with conjunctivochalasis often present with other ocular surface issues beyond conjunctivochalasis itself, such as insufficient tear secretion, reduced lipid layer thickness, and other dry eye-related problems. Therefore, a comprehensive approach emphasizing tear dynamics should be adopted during treatment.
3.Construction and application of a system for rational drug use for prescriptions from internet hospitals and external prescriptions and medical insurance fund control based on a pre-review prescription system
Yi GE ; Xiaolan WANG ; Junping HAN ; Bo LYU ; Yu GUAN ; Feng XU ; Aiming SHI
China Pharmacy 2026;37(5):584-588
OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions, as well as to review the payment methods of drugs (including in-hospital and external drug dispensing). METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally, an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 (before the system upgrade) and May to August 2025 (after the system upgrade). RESULTS After the upgrade of the pre-prescription review system, the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval (CI)=0.3%-6.7%, P =0.037 ] ; the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level (95%CI=31.6%-88.5%, P =0.026), and the average monthly sequential decrease was 29.5% (95%CI=12.2%-43.4%, P =0.012). Moreover, the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade, a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs, and strengthens the supervision of off-label drug use, achieving dual guarantees of clinical rationality and medical insurance compliance.
4.Clinical Efficacy of Modified Linggui Zhugan Tang in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome of Spleen Deficiency and Dampness Obstruction with Blood Stasis Type and Its Effect on MIF, miR-223, and IL-18
Jun ZHANG ; Mengmei WEI ; Bo LI ; Yi YANG ; Changhui LINGHU ; Mingchang ZHANG ; Zhengxing GE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):171-179
ObjectiveTo investigate the intervention effects of modified Linggui Zhugan Tang (LGZGT) on patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) of the spleen deficiency and dampness obstruction with blood stasis type, reveal its possible mechanisms, and provide a theoretical basis for the clinical treatment of OSAHS with traditional Chinese medicine (TCM). MethodsEighty OSAHS patients with spleen deficiency and dampness obstruction with blood stasis were randomly assigned to a control group and an observation group (1∶1) using a random number table, with 40 patients in each group. The control group received standard basic treatment combined with oral Doxofylline tablets, while the observation group received standard basic treatment combined with modified LGZGT. Serum levels of macrophage migration inhibitory factor (MIF), microRNA-223 (miR-223), and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of MIF, miR-223, and IL-18 were measured by real-time quantitative polymerase chain reaction (Real-time PCR). After two months of treatment, the total clinical efficacy, apnea-hypopnea index (AHI), lowest nocturnal oxygen saturation (LSpO2), body mass index (BMI), TCM syndrome scores, and expression levels of MIF, miR-223, and IL-18 before and after treatment were compared between the two groups. Correlations between MIF, miR-223, IL-18 and AHI and LSpO2 were also analyzed. ResultsCompared with the control group, the observation group showed a significantly higher total clinical effective rate (P<0.01, Z=-3.49). Within the control group, no significant changes were observed in AHI, LSpO2, BMI, TCM syndrome scores, or MIF, miR-223, IL-18 levels and their mRNAs after treatment. In the observation group, AHI, BMI, TCM syndrome scores, and MIF and IL-18 levels and their mRNAs decreased significantly, while LSpO2 increased significantly (P<0.01). After treatment, compared with the control group, the observation group exhibited significantly lower AHI, BMI, TCM syndrome scores, and MIF and IL-18 levels and their mRNAs, and significantly higher LSpO2 (P<0.01). Correlation analysis showed that MIF and IL-18 were positively correlated with AHI (P<0.01) and negatively correlated with LSpO2 (P<0.01), whereas miR-223 was negatively correlated with AHI (P<0.01) and positively correlated with LSpO2 (P<0.01). ConclusionModified LGZGT may improve OSAHS of the spleen deficiency and dampness obstruction with blood stasis type by reducing airway inflammatory factors, alleviating airway inflammation, relieving airway edema and stenosis, and improving airway obstruction.
5.The Current Issues and Thoughts on the Empowerment of Famous Doctors' Experience Inheritance by Artificial Intelligence
Xiaochen JIANG ; Fudong LIU ; Chuanlong ZHANG ; Yi LI ; Qian SHEN ; Bo PANG
Journal of Traditional Chinese Medicine 2026;67(7):710-715
In the context of the modernization of traditional Chinese medicine (TCM), the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system, such as the homogenization of talent cultivation models, lack of standardized mentoring practices, and monotonous evaluation method, which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence (AI)-assisted inheritance of famous doctors' experiences, this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions, including data authenticity assurance, interdisciplinary collaboration mechanisms, and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era, aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation", providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.
6.Quality Evaluation of Naomaili Granules Based on Multi-component Content Determination and Fingerprint and Screening of Its Anti-neuroinflammatory Substance Basis
Ya WANG ; Yanan KANG ; Bo LIU ; Zimo WANG ; Xuan ZHANG ; Wei LAN ; Wen ZHANG ; Lu YANG ; Yi SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):170-178
ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics, and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography (UPLC) fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated, and 23 of them were identified and assigned. In 27 batches of Naomaili granules, the mass fractions of 14 components that were stachydrine hydrochloride, leonurine hydrochloride, calycosin-7-O-glucoside, calycosin,tanshinoneⅠ, cryptotanshinone, tanshinoneⅡA, ginsenoside Rb1, notoginsenoside R1, ginsenoside Rg1, paeoniflorin, albiflorin, lactiflorin, and salvianolic acid B were found to be 2.902-3.498, 0.233-0.343, 0.111-0.301, 0.07-0.152, 0.136-0.228, 0.195-0.390, 0.324-0.482, 1.056-1.435, 0.271-0.397, 1.318-1.649, 3.038-4.059, 2.263-3.455, 0.152-0.232, 2.931-3.991 mg∙g-1, respectively. Multivariate statistical analysis showed that paeoniflorin, ginsenoside Rg1, ginsenoside Rb1 and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them, salvianolic acid B and ginsenoside Rb1 had strong anti-inflammatory activity, with IC50 values of (36.11±0.15) mg∙L-1 and (27.24±0.54) mg∙L-1, respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out, and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.
7.Role of Peripheral 5-hydroxytryptamine in Toll-like Receptor 4-mediated Diabetes Mellitus Type 2
Yi-Ying ZHANG ; Ping ZHANG ; Bo YANG ; Xiao-Tong CHANG
Progress in Biochemistry and Biophysics 2025;52(5):1070-1080
In recent years, the prevalence of diabetes has continued to rise, with diabetes mellitus type 2 (T2DM) being the most common form. T2DM is characterized by chronic low-grade inflammation and disruptions in insulin metabolism. Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that, upon activation, upregulates pro-inflammatory cytokines via the nuclear factor κB (NF‑κB) pathway, thereby contributing to the pathogenesis of T2DM. Peripheral 5-hydroxytryptamine (5-HT), primarily synthesized by enterochromaffin (EC) cells in the gut, interacts with 5-hydroxytryptamine receptors (5-HTRs) in key insulin-target tissues, including the liver, adipose tissue, and skeletal muscle. This interaction influences hepatic gluconeogenesis, fat mobilization, and the browning of white adipose tissue. Elevated peripheral 5-HT levels may disrupt glucose and lipid metabolism, thereby contributing to the onset and progression of T2DM. Within mitochondria, 5-HT undergoes degradation and inactivation through the enzymatic action of monoamine oxidase A (MAO-A), leading to the generation of reactive oxygen species (ROS). Excessive ROS production and accumulation can induce oxidative stress, which may further contribute to the pathogenesis of T2DM. Platelets serve as the primary reservoir for5-HT in the bloodstream. The activation of the TLR4 signaling pathway on the platelet surface, coupled with reduced expression of the 5-HT transporter on the cell membrane, leads to elevated serum 5-HT levels, potentially accelerating the progression of T2DM. Therefore, inhibition of TLR4 and reduction of peripheral 5-HT levels could represent promising therapeutic strategies for T2DM. This review explores the synthesis, transport, and metabolism of peripheral 5-HT, as well as its role in TLR4-mediated T2DM, with the aim of providing novel insights into the clinical diagnosis, treatment, and evaluation of T2DM.
8.Research on BP Neural Network Method for Identifying Cell Suspension Concentration Based on GHz Electrochemical Impedance Spectroscopy
An ZHANG ; A-Long TAO ; Qi-Hang RAN ; Xia-Yi LIU ; Zhi-Long WANG ; Bo SUN ; Jia-Feng YAO ; Tong ZHAO
Progress in Biochemistry and Biophysics 2025;52(5):1302-1312
ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.
9.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.
10.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.

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