1.Mechanistic study on ITGA6 regulation of abdominal wall endometriosis via the PI3K/AKT signaling pathway
Rong GU ; Hailiang HUANG ; Xinrui WANG ; Hanlu LI ; Kaijiang LIU ; Ying ZHU
Acta Universitatis Medicinalis Anhui 2026;61(1):67-74
ObjectiveTo investigate the differential expression of integrin alpha-6(ITGA6) in abdominal wall endometriosis (AWE) tissues and its molecular mechanisms in regulating AWE. Methods36 AWE lesions were designated as the experimental group, while 36 cases of normal endometrial tissues served as the controls. Differential expression of ITGA6 between the two groups was assessed through immunohistochemical (IHC) staining. Human ITGA6 gene-specific interference sequences were designed, synthesized, and packaged into lentiviral vectors to establish the Ishikawa cell line with ITGA6-knockdown. Similarly, the ITGA6-overexpression cell line was constructed using the coding sequence (CDS) of the gene. Real-time PCR and Western blot were performed to detect changes in epithelial-mesenchymal transition(EMT)-related markers and angiogenesis-related indicators. Cell invasion and migration capabilities were assessed by Cell Scratch and Transwell assays. Furthermore, Western blot was conducted to profile PI3K/AKT pathway dynamics. ResultsEctopic endometrial tissues exhibited a marked increase in the number of ITGA6-positive cells and their expression intensity compared to eutopic endometrium (each P < 0.001). Compared with the NC group, the ITGA6-knockdown group showed significantly reduced expression of N-cadherin, VEGF, and TGF-β1 (all P < 0.01), while E-cadherin expression was markedly increased (P < 0.01). Concomitantly, the invasion and migration capacities of ITGA6-low expression were significantly impaired (P < 0.001 for both), accompanied by a marked reduction in AKT and phosphorylated AKT(p-AKT) levels (P < 0.001). Conversely, overexpressing ITGA6 resulted in opposite effects. ConclusionITGA6 modulates EMT and angiogenesis in Ishikawa cells via the PI3K/AKT signaling pathway, thereby enhancing cell invasion and migration capabilities, which contributes to the pathogenesis of AWE.
2.Platelet methyltransferase-like protein 4-mediated mitochondrial DNA metabolic disorder exacerbates oral mucosal immunopathology in hypoxia.
Yina ZHU ; Meichen WAN ; Yutong FU ; Junting GU ; Zhaoyang REN ; Yun WANG ; Kehui XU ; Jing LI ; Manjiang XIE ; Kai JIAO ; Franklin TAY ; Lina NIU
International Journal of Oral Science 2025;17(1):49-49
Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N6-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism*
;
Mouth Mucosa/pathology*
;
Hypoxia/immunology*
;
Methyltransferases/metabolism*
;
Blood Platelets/metabolism*
;
Animals
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Periodontitis/immunology*
;
Humans
;
Platelet Activation
;
Mice
3.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
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Mendelian Randomization Analysis
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Gallstones/complications*
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Female
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Male
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Cholecystectomy/statistics & numerical data*
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Middle Aged
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Risk Factors
;
Aged
;
Adult
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Neoplasms/etiology*
;
Stomach Neoplasms/epidemiology*
4.Effects of acupuncture needle modification on acupuncture analgesia.
Ming-Zhu SUN ; Xin WANG ; Ying-Chen LI ; Yu-Hang LIU ; Yi YU ; Liu-Jie REN ; Wei GU ; Wei YAO
Journal of Integrative Medicine 2025;23(1):66-78
OBJECTIVE:
The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation.
METHODS:
Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia.
RESULTS:
The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle.
CONCLUSION
Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles
;
Acupuncture Analgesia/methods*
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Animals
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Rats
;
Male
;
Acupuncture Points
;
Rats, Sprague-Dawley
5.Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis.
Meng-Jie ZHU ; Yi-Jie SONG ; Pei-Li RAO ; Wen-Yi GU ; Yu XU ; Hong-Xi XU
Journal of Integrative Medicine 2025;23(3):297-308
OBJECTIVE:
Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis.
METHODS:
An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels.
RESULTS:
PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability.
CONCLUSION
PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure. Please cite this article as: Zhu MJ, Song YJ, Rao PL, Gu WY, Xu Y, Xu HX. Therapeutic role of Prunella vulgaris L. polysaccharides in non-alcoholic steatohepatitis and gut dysbiosis. J Integr Med. 2025; 2025; 23(3): 297-308.
Animals
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Non-alcoholic Fatty Liver Disease/drug therapy*
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Male
;
Dysbiosis/drug therapy*
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Mice, Inbred C57BL
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Gastrointestinal Microbiome/drug effects*
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Polysaccharides/therapeutic use*
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Prunella/chemistry*
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Mice
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Liver/metabolism*
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Plant Extracts/therapeutic use*
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Disease Models, Animal
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Diet, High-Fat
6.Current situation of clinical trial registration in acupuncture anesthesia: A scoping review.
Yue LI ; You-Ning LIU ; Zhen GUO ; Mu-En GU ; Wen-Jia WANG ; Yi ZHU ; Xiao-Jun ZHUANG ; Li-Ming CHEN ; Jia ZHOU ; Jing LI
Journal of Integrative Medicine 2025;23(3):256-263
BACKGROUND:
Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias.
OBJECTIVE:
Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP).
SEARCH STRATEGY:
We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics.
INCLUSION CRITERIA:
Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review.
DATA EXTRACTION AND ANALYSIS:
Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment.
RESULTS:
A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41).
CONCLUSION
The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans
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Acupuncture Analgesia
;
Acupuncture Therapy
;
Anesthesia
;
Clinical Trials as Topic
;
Registries
7.Effects of superoxide dismutase inhibition of AFP expression on the malignant biological behavior of PLC/PRF/5 liver cancer cells
Yi CHEN ; Baoying CHEN ; Yuli ZHOU ; Haixia XU ; Yu CAO ; Yue GU ; Mingyue ZHU ; Mengsen LI
China Pharmacy 2025;36(17):2120-2126
OBJECTIVE To explore the effect of superoxide dismutase (SOD) administration on the malignant behavior of PLC/PRF/5 liver cancer cells, and analyze the correlation between SOD and alpha-fetoprotein (AFP) expression, to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02, AFP- negative human liver cancer cells HLE, and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP, SOD and activity of SOD in cells before and after changing AFP expression; the effects of different concentrations of SOD [0 (control), 0.188, 0.375, 0.75, 1.5, 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein (Src) in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group, the expression levels of SOD1 and SOD2, and SOD activity in PLC/PRF/5 cells were significantly reduced (P<0.05). After down-regulating AFP expression in PLC/PRF/ 5 cells, compared with PLC/PRF/5 group, the expression levels of SOD1 and SOD2, as well as SOD activity, were significantly increased in the PLC/PRF/5-shAFP group (low-expression) (P<0.05). After 48 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups were significantly reduced (P<0.05); after 72 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, and 1.5 U/mL SOD groups were significantly reduced (P<0.05 or P<0.01). Compared with control group, proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups (P<0.05 or P<0.01). Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression, the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups (over-expression) after up-regulating SOD1 and SOD2 expression were significantly reduced (P<0.05). CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells, and the expression level and activity of SOD are negatively correlated with AFP.
8.RNF115 deficiency upregulates autophagy and inhibits hepatocellular carcinoma growth.
Zhaohui GU ; Jinqiu FENG ; Shufang YE ; Tao LI ; Yaxin LOU ; Pengli GUO ; Ping LV ; Zongming ZHANG ; Bin ZHU ; Yingyu CHEN
Chinese Medical Journal 2025;138(6):754-756
9.Z-DNA-binding protein 1-mediated programmed cell death: Mechanisms and therapeutic implications.
Yuwei HUANG ; Lian WANG ; Yanghui ZHU ; Xiaoxue LI ; Yingying DAI ; Gu HE ; Xian JIANG
Chinese Medical Journal 2025;138(19):2421-2451
Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.
10.Effects of Prognostic Nutritional Index and Systemic Inflammatory Response Index on Short-Term Efficacy and Prognosis in Patients with Peripheral T-Cell Lymphoma.
Zi-Qing HUANG ; Yan-Hui LI ; Bin LYU ; Xue-Jiao GU ; Ming-Xi TIAN ; Xin-Yi LI ; Yan ZHANG ; Xiao-Qian LI ; Ying WANG ; Feng ZHU
Journal of Experimental Hematology 2025;33(5):1350-1357
OBJECTIVE:
To investigate the predictive value of the prognostic nutritional index (PNI) and systemic inflammatory response index (SIRI) for short-term efficacy and prognosis in newly treated patients with peripheral T-cell lymphoma (PTCL).
METHODS:
The general data, laboratory indicators, disease stage and other clinical data of 91 newly treated PTCL patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2023 were retrospectively analyzed. The optimal cutoff values for PNI and SIRI were determined using receiver operating characteristic (ROC) curves, and the patients were stratified into groups based on these cutoffs to compare clinical features and short-term efficacy between the different groups. Kaplan-Meier method was used to plot survival curves, and univariate and multivariate analyses were performed to identify the factors affecting overall survival (OS).
RESULTS:
The optimal cutoff values for PNI and SIRI were 45.30 and 1.74×109/L, respectively. Patients in different PNI groups showed statistically significant differences in age, Ann Arbor stage, lactate dehydrogenase (LDH) level, international prognostic index (IPI), prognostic index for PTCL-not otherwise specified (PIT), pathological subtypes, and complete response (CR) rate (P < 0.05). PTCL patients in different SIRI groups exhibited significant differences in Ann Arbor stage, LDH level, IPI score, PIT score, and CR rate (P < 0.05). Logistic regression analysis showed that age ≥60 years old (OR =2.750), Ann Arbor stage Ⅲ-Ⅳ (OR =5.200), IPI score ≥2 (OR =7.650), low PNI (OR =3.296), and high SIRI (OR =3.130) were independent risk factors affecting treatment efficacy in PTCL patients (P < 0.05). Cox proportional hazards regression model analysis showed that low PNI and elevated β2-microglobulin (β2-MG) levels were independent risk factors affecting OS (P < 0.05).
CONCLUSION
PNI and SIRI have certain application value in evaluating short-term efficacy and prognosis in patients with PTCL. Compared with SIRI, PNI demonstrates greater predictive value for patient prognosis.
Humans
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Prognosis
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Lymphoma, T-Cell, Peripheral/therapy*
;
Retrospective Studies
;
Nutrition Assessment
;
Male
;
Female
;
Middle Aged
;
ROC Curve
;
Inflammation

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