1.A bibliometric and visual analysis of the literature published in the journal of Organ Transplantation since its inception
Xi CAO ; Tao HUANG ; Qiwei YANG ; Lin YU ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2026;17(1):133-142
Objective To systematically analyze the literature characteristics of Journal of Organ Transplantation since its inception. Methods Using the China National Knowledge Infrastructure (CNKI) academic journal full-text database as the data source, all articles published in the Journal of Organ Transplantation from January 2010 to August 2025 were retrieved. After excluding non-academic papers, a total of 1 568 research papers were included. R language 4.3.0, Bibliometrix package 3.2.1, and Citespace software were used to analyze the number of publications, publishing institutions, authors, keywords and other aspects. Results The number of publications in Journal of Organ Transplantation increased from an average of 82 articles per year in the early years after its inception to 113 articles per year in recent years, a growth of 37.8%. The geographical distribution of publishing institutions covers 32 provinces, cities and autonomous regions nationwide, mainly concentrated in the South China, East China and North China regions, and has now basically covered the central and western regions in recent years. The author collaboration network includes 45 authors distributed across 7 major collaboration clusters, forming a stable multi-level national research system centered on key university-affiliated hospitals. The high-frequency keywords are dominated by "liver transplantation" (425 times) and "kidney transplantation" (396 times). The theme evolution shows a clear three-stage characteristic: initially focusing on clinical technology application, deepening to immune mechanism exploration in the middle stage, and recently (since 2022) focusing on cutting-edge research areas such as xenotransplantation. Conclusions Journal of Organ Transplantation has witnessed the rapid development of China's organ transplantation cause, fully reflecting the research status and trends in China's organ transplantation field, and has provided an important platform for the future development and international cooperation in China's organ transplantation field.
2.Correlation of sleep problems with emotional and behavioral problems among children with cerebral palsy
YANG Jiewen, HUANG Shaoyi, HUANG Shan, DENG Haorong, KANG Tao, CHEN Yajun
Chinese Journal of School Health 2025;46(2):181-185
Objective:
To investigate the correlation of emotional and behavioral problems with sleep problems in children with cerebral palsy, so as to provide reference for intervention of emotional and behavioral problems in children.
Methods:
A cross sectional survey was conducted, and 402 children aged 6-18 with cerebral palsy who were adopted by social welfare institutions in Guangzhou City from January 2023 to January 2024 were selected to investigate their full time nurses. The Parents Strengths and Difficulties Questionnaire (SDQ) was used to assess the emotional and behavioral problems of children with cerebral palsy, and the Children s Sleep Habits Questionnaire (CSHQ) was used to assess sleep problems. Multiple linear regression analysis was used to analyze the correlation between the sleep problem of children with cerebral palsy and the emotional and behavioral problems.
Results:
The prevalence of emotional and behavioral difficulties among children with cerebral palsy was 15.7%. The median sleep problem score of children with emotional and behavioral problems [37.0(36.0, 41.0)] was significantly higher than that of children without emotional and behavioral [35.0(34.0, 36.0)] ( Z =-5.74, P <0.01). The results of multiple linear regression analysis showed that after adjusting covariables such as age, gender, cerebral palsy classification, language retardation, visual impairment and epilepsy, the total sleep problem score of children with cerebral palsy was positively correlated with the total difficulty score ( β= 0.28, 95%CI =0.17-0.34, P <0.05).
Conclusions
Sleep problems in children with cerebral palsy are associated with emotional and behavioral difficulties. Understanding of the management of sleep problems in children with cerebral palsy should be enhanced to reduce the incidence of emotional and behavioral problems in children with cerebral palsy.
3.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
4.Efficacy Evaluation of Initial Double Filtration Plasmapheresis in NMOSD with Respiratory Insufficiency
Sai ZHANG ; Xi CHEN ; Tao ZENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):154-160
ObjectiveTo discuss the clinical manifestations and image features of Neuromyelitis Optica Spectrum Disorder (NMOSD)with respiratory insufficiency. We present a retrospective review about the use of double filtration plasmapheresis in the treatment of the acute attack of NMOSD in these patients. MethodsAll of our patients with central respiratory insufficiency who suffered attacks of NMOSD were retrospectively considered for inclusion. Extended Disability Status Scale(EDSS)scores were compared within six months after double membrane filtration plasma exchange. ResultsThe clinical data of the six patients included were analyzed. Magnetic Resonance Imaging confirmed that the demyelinating plaques in our patients could involve the medulla oblongata and upper spinal cord. They were managed by plasma exchange given as an initial therapy. The clinical symptoms improved significantly and the patients were successfully withdrawn from the ventilator,with EDSS scores significantly reduced (P<0.001). ConclusionDemyelination of medulla oblongata and upper spinal cord in NMOSD may lead to acute life-threatening respiratory compromise, and early initiation of double filtration plasmapheresis can be a safe and effective treatment.
5.Dynamic immunological characteristics in acute rejection model of cervical heterotopic heart transplantation in mice
Xi CAO ; Tao HUANG ; Jiwei YANG ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2025;16(2):256-263
Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8+ T cell infiltration. The proportion of CD8+ T cells in the spleen continued to rise post-operation, while the proportion of CD4+ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.
6.Single-center experience in the diagnosis and treatment of gastrointestinal bleeding after renal transplantation
Organ Transplantation 2025;16(3):467-473
Objective To analyze the clinical characteristics of patients with gastrointestinal bleeding after renal transplantation and summarize the diagnostic and therapeutic experience. Methods Clinical data of 16 patients with gastrointestinal bleeding after renal transplantation admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to January 2025 were collected, including clinical manifestations, laboratory tests and auxiliary examination results such as gastroscopy and colonoscopy. The bleeding sites, causes, treatment plans and outcomes of the patients were analyzed, and relevant literature was reviewed. Results Among the 16 patients with gastrointestinal bleeding, 12 had upper gastrointestinal bleeding (3 with esophageal bleeding, 7 with gastric bleeding and 2 with duodenal bleeding) and 4 had lower gastrointestinal bleeding (2 with ileal bleeding and 2 with anal bleeding). Among the 16 patients, the 4 with lower gastrointestinal bleeding all presented with hematochezia. Of the 12 with upper gastrointestinal bleeding, 2 patients only had positive fecal occult blood and decreased hemoglobin levels without hematemesis or melena, 9 patients had melena and 1 patient had hematemesis. The hemoglobin levels of the 16 patients were (71±18) g/L. One patient had symptoms of shock, 9 had symptoms of anemia such as dizziness, fatigue and chest tightness, and 6 had good general conditions. Among the 16 patients, 10 had mild gastrointestinal bleeding and stable general conditions, which were curable by drugs. Two patients with peptic ulcers and exposed vessels on gastroscopy were treated with hemostasis by titanium clips. One patient with gastroesophageal tear was treated with hemostasis by titanium clips. One patient with esophageal variceal rupture bleeding was treated with endoscopic variceal ligation. One patient with hemorrhoidal bleeding underwent selective annual resection of the superior hemorrhoidal mucosa with stapled hemorrhoidopexy. One patient with active ileal bleeding on emergency enhanced abdominal CT was treated with endovascular embolization of the mesenteric artery. One patient was discharged automatically due to coma caused by extensive cerebral infarction, and the remaining patients were all cured and discharged with good prognosis. Conclusions Gastrointestinal bleeding after renal transplantation has diverse clinical manifestations, varying severity and many causes. Early diagnosis and treatment should be actively carried out. In addition to drug therapy, endoscopic, interventional or surgical treatment may be used when necessary to improve the diagnostic and therapeutic effects and minimize the functional damage of gastrointestinal bleeding to the transplant kidney.
7.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
8.Zhenzhu Tiaozhi Capsules Reduce Renal Lipid Deposition and Inflammation in Mouse Model of Diabetic Kidney Disease via SCAP-SREBP-1c/NLRP3 Signaling Pathway
Tao ZHANG ; Jie TAO ; Yinghui ZHANG ; Yiqi YANG ; Xianglu RONG ; Jiao GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):114-121
ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin (STZ) at 40 mg·kg-1 for 5 days combined with a high-fat diet (HFD). Fasting blood glucose (FBG) ≥ 11.1 mmol·L-1, increased urine volume, and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows: Blank, model, low- and high-dose (0.98 and 1.96 g·kg-1, respectively) Zhenzhu Tiaozhi capsules, and losartan potassium (30 mg·kg-1), with six mice in each group. After 12 weeks of continuous gavage, urine and kidney specimens were collected, and the 24-h urinary protein and the urinary albumin-to-creatinine ratio (UACR) in mice were measured. Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c), and NOD-like receptor protein 3 (NLRP3) in the renal tissue. ResultsCompared with the blank group, the model group showed increases in 24-h urinary protein and UACR (P<0.05), glomeruli exhibiting capsule adhesion, collagen fiber deposition, mesangial proliferation, and inflammatory cell infiltration, elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), reduced positive expression of nephrin (P<0.05), increased lipid deposition (P<0.05), and up-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. Compared with the model group, the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR (P<0.05), and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein (P<0.05). Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated, with reduced inflammatory infiltration, collagen fiber deposition, and mesangial proliferation, and increased positive expression of nephrin in the renal tissue (P<0.05). In addition, all the treatment groups showed reduced lipid droplets (P<0.05), lowered levels of IL-1β, IL-6, and TNF-α (P<0.05), and down-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway, which reduces renal lipid deposition and inflammation.
9.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.
10.Zhenzhu Tiaozhi Capsules Reduce Renal Lipid Deposition and Inflammation in Mouse Model of Diabetic Kidney Disease via SCAP-SREBP-1c/NLRP3 Signaling Pathway
Tao ZHANG ; Jie TAO ; Yinghui ZHANG ; Yiqi YANG ; Xianglu RONG ; Jiao GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):114-121
ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin (STZ) at 40 mg·kg-1 for 5 days combined with a high-fat diet (HFD). Fasting blood glucose (FBG) ≥ 11.1 mmol·L-1, increased urine volume, and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows: Blank, model, low- and high-dose (0.98 and 1.96 g·kg-1, respectively) Zhenzhu Tiaozhi capsules, and losartan potassium (30 mg·kg-1), with six mice in each group. After 12 weeks of continuous gavage, urine and kidney specimens were collected, and the 24-h urinary protein and the urinary albumin-to-creatinine ratio (UACR) in mice were measured. Hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein (SCAP), sterol regulatory element-binding protein-1c (SREBP-1c), and NOD-like receptor protein 3 (NLRP3) in the renal tissue. ResultsCompared with the blank group, the model group showed increases in 24-h urinary protein and UACR (P<0.05), glomeruli exhibiting capsule adhesion, collagen fiber deposition, mesangial proliferation, and inflammatory cell infiltration, elevated levels of IL-1β, IL-6, and TNF-α (P<0.05), reduced positive expression of nephrin (P<0.05), increased lipid deposition (P<0.05), and up-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. Compared with the model group, the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR (P<0.05), and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein (P<0.05). Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated, with reduced inflammatory infiltration, collagen fiber deposition, and mesangial proliferation, and increased positive expression of nephrin in the renal tissue (P<0.05). In addition, all the treatment groups showed reduced lipid droplets (P<0.05), lowered levels of IL-1β, IL-6, and TNF-α (P<0.05), and down-regulated expression of SCAP, SREBP-1c, and NLRP3 (P<0.05) in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway, which reduces renal lipid deposition and inflammation.


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