1.Laboratorydiagnosis and perinatal blood management of HDFN in a Jr(a-) pregnant woman
Pan XIAO ; Ke SONG ; Wei YANG ; Lingling LI ; Yi LIU ; Chunya MA ; Yang YU
Chinese Journal of Blood Transfusion 2026;39(2):248-255
Objective: To report the antibody identification, blood management during pregnancy and the monitoring process of fetal hemolytic disease of fetus and newborn (HDFN) in a pregnant woman with a history of blood transfusion and pregnancy who developed anti-Jr
. Methods: Saline tube technique and anti-human globulin technique were used for maternal blood typing, unexpected antibody screening and identification, as well as for determining antibody titer and IgG subclasses. PCR-SSP was employed for genotyping of 18 blood group systems. Next-generation sequencing (NGS) was utilized for gene sequencing of 38 blood group systems. Sanger sequencing was applied to verify rare blood group mutations detected by NGS and to investigate the corresponding rare blood group genes in family members. Blood preparation was achieved through anemia management in prenatal clinics and autologous blood collection during pregnancy. The newborn underwent the three primary tests for HDFN and plasma IgG subclass testing. Results: The pregnant woman's blood type was B, RhD positive, with a positive unexpected antibody screen, and the antibody identification pattern was consistent with a high-frequency antigen antibody. Gene sequencing revealed a homozygous ABCG2 c.376C>T mutation in the woman, resulting in the Jr(a-) phenotype, and anti-Jr
antibody was present in her plasma. No compatible Jr(a-) blood was found among family members. The maternal anti-Jr
IgG titer remained stable at 256 during pregnancy, with no detectable IgG1 or IgG3 subclasses against the Jr
antigen. A total of 800 mL of autologous blood was collected in two stages during pregnancy. The newborn was B, RhD positive, Jr(a+), with a positive unexpected antibody screen (anti-Jr
). IgG subclass typing detected no IgG1 or IgG3. The direct antiglobulin test was positive, while the acid elution test was negative. Conclusion: The combination of serology and blood group genetic analysis provides a diagnostic basis for identifying antibodies to high-frequency antigens. Managing perinatal anemia and implementing staged autologous blood storage can secure blood supply for the perioperative period. IgG antibody subclass typing offers a reference for clinical assessment and prevention of HDFN.
2.Practice and reflection on ethical review of multicentre studies in a tertiary hospital
Lingling YU ; Wei LIU ; Pengjun ZHANG
Chinese Medical Ethics 2025;38(1):58-62
ObjectiveTo analyse the implementation of mutual recognition of ethical review in a tertiary hospital, providing ideas for exploring ethical review of multicenter studies. MethodsThe ethical review of multicenter studies conducted by the hospital from 2018 to 2022 was analyzed. ResultsA total of 1,582 projects were reviewed in the hospital from 2018 to 2022, of which 773 (48.9%) were multicentre studies. In multicenter study projects, 70.4% of the studies were conducted as a participating unit. Mutual recognition of ethical review and fast review were implemented for all participating projects. After a rapid review of 24 studies, the presiding committee recommended submitting them for conference review. The reasons for the transfer to conference review included issues with the study protocol (11 projects), informed consent (12 projects), and other supporting documents (5 projects). Twenty-one studies were eventually approved by the ethics committee after modification, and 3 studies were not approved by the ethics committee because the sponsor refused to modify the study protocols. ConclusionFor participating in multicentre studies, the ethics committees of participating units implement mutual recognition of ethical reviews and adopt a rapid review approach to review all study data, which can achieve both quality and efficiency.
3.Identifying neurophysiological characteristics for early recognition of bipolar disorder based on gamma band effective connectivity of the prefrontal-striatal circuit
Wei YOU ; Lingling HUA ; Yishan DU ; Junling SHENG ; Rui YAN ; Qing LU ; Zhijian YAO
Chinese Journal of Psychiatry 2025;58(2):125-133
Objective:This study aims to analyze the gamma band effective connectivity characteristics of the prefrontal-striatal circuitry in bipolar disorder patients with and without a history of manic episodes, as well as in major depressive disorder patients, during the recognition of positive emotional faces, this study aims to identify unique neurophysiological features that may aid in the early detection of bipolar disorder.Methods:This retrospective study collected clinical data and magnetoencephalography (MEG) imaging data from patients performing a positive emotional face recognition task at the Affiliated Brain Hospital of Nanjing Medical University from May 2009 to December 2019. The study included 75 patients with major depressive disorder and 29 patients with bipolar disorder in a depressive episode (rBD group). Concurrently, 39 age-and gender-matched healthy controls (HC group) were recruited. After a follow-up period of at least 5 years, 23 out of the 75 patients with major depressive disorder converted to bipolar disorder (ctBD group), while the remaining 52 who did not convert maintained a diagnosis of major depressive disorder.Results:There were statistically significant differences in gamma-band effective connectivity in the prefrontal-striatal circuit when recognizing positive emotional faces among the converted to bipolar disorder (ctBD), raw bipolar disorder, major depressive disorder, and HC groups ( H=9.04, 10.30, 8.30, 13.43, 14.38, 12.62, 9.82, 8.94, 24.62, 7.89, 18.53, 9.97, 9.58, 12.79, P<0.05). The ctBD group, rBD group, and major depressive group all showed reduction in effective connectivity from the right orbital inferior frontal gyrus (ORBinf.R) to the left orbital inferior frontal gyrus (ORBinf.L) [ Z=-1.98, -3.38, -2.88], from the right orbital inferior frontal gyrus to the right ventral striatum (VS.R) ( Z=-2.05, -2.76, -2.11; P<0.05) and from the left ventral striatum (VS.L) to the left orbital middle frontal gyrus (ORBmid.L) ( Z=-2.76, -1.98, -2.43; P<0.05). Among the disease groups, the ctBD group showed significantly enhanced effective connectivity strength compared to the major depressive group from the right amygdala (AMYG.R) to the left orbital inferior frontal gyrus(0.04(0.03, 0.08)), from the right amygdala to the left ventral striatum(0.05(0.03, 0.09)), and from the right ventral striatum to the right anterior cingulate and paracingulate gyri (ACG.R) (0.04(0.02, 0.08)) ( Z=4.17, 3.70, 3.35; P<0.001).The ctBD group also exhibited enhanced effective connectivity compared to the rBD group from ORBinf.R to the ACG.R, fron the AMYG.R to the ORBinf.L, from the AMYG.R to the VS.L, and from the VS.R to the ACG.R ( Z=2.05, 4.61, 3.60, 3.04; P<0.05).The rBD group demonstrated reduced effective connectivity compared to the major depressive disorder group from the right orbital middle frontal gyrus(ORBmid.R) to the left anterior cingulate and paracingulate gyri (ACG.L), ORBinf.R to the ACG.R and from the ORBinf.R to the AMYG.R ( Z=-2.12, -2.40, -2.22; P<0.05). Conclusion:There are significant differences in the gamma-band effective connectivity characteristics of the prefrontal-striatal pathway when recognizing positive emotional faces between patients with bipolar disorder in depressive episodes and those with depression, as well as differences between bipolar depressed patients with and without a history of manic episodes.
4.2024 Update of Chinese Guidelines for the Management of Hyperuricemia and Gout Part Ⅱ: Recommendations for Patients with Common Comorbidities
Changgui LI ; Mingshu SUN ; Zhen LIU ; Detian LI ; Changqian WANG ; Zibin TIAN ; Yuxiang DAI ; Zhe FENG ; Chengfu XU ; Dongbao ZHAO ; Feng WEI ; Bo BAN ; Chao XIE ; Zhenmei AN ; Jia LIU ; Zhuo LI ; Yuwei HE ; Xinde LI ; Fei YAN ; Lin HAN ; Lidan MA ; Xiaoyu CHENG ; Tian LIU ; Xufei LUO ; Lingling CUI ; Ying GONG ; Can WANG ; Yaolong CHEN ; Zhaohui LYU ; Yip Ronald ML ; Jiajun ZHAO
Chinese Journal of Endocrinology and Metabolism 2025;41(11):918-929
The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.
5.Significance of enteric nervous system disorders in Crohn's disease
Xue DENG ; Lingling YANG ; Yue ZHANG ; Hong GUO ; Wei WANG ; Xuefeng TANG
Chinese Journal of Inflammatory Bowel Diseases 2025;09(2):158-163
Crohn 's disease (CD) is an intestinal inflammatory disease of unknown etiology, the pathophysiological mechanism is still unclear. The enteric nervous system (ENS) is responsible for the autonomous regulation of intestinal function. Therefore, ENS dysfunction may be the core of the pathophysiological mechanism of CD. Here, we review the pathophysiological mechanism by which ENS contributes to the development of CD, with a focus on the role of aberrant histological manifestations of ENS and plexitis in predicting the recurrence of CD following surgery.
6.Diagnostic value of fetal cardiac ultrasound screening views in the first trimester for congenital heart disease
Chengcheng WU ; Chunya JI ; Liqun FENG ; Wei SHAO ; Naimin SUN ; Jun ZHANG ; Zhong YANG ; Chen LING ; Lingling SUN ; Qi PAN ; Xuedong DENG ; Linliang YIN
Chinese Journal of Ultrasonography 2025;34(9):799-804
Objective:To investigate the diagnostic value of fetal cardiac ultrasound view visualization in the first trimester for congenital heart disease(CHD).Methods:A retrospective analysis was performed on 13 323 singleton fetuses who underwent first-trimester(11-13 +6 weeks)ultrasound screening at the Ultrasound Medicine Center,the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to June 2024. Cardiac views including the four-chamber view(4CV),left ventricular outflow tract view(LVOT),and Results:The study group showed significantly higher rates of "poorly visualized" 4CV,LVOT,and 3VT than the control group(2.70% vs. 0.14%, P=0.005;36.49% vs. 4.76%, P<0.001;36.49% vs.2.46%, P<0.001). The efficacies of combination 1(any view abnormal)and combination 2(any view "poorly visualized" or "abnormal")were comparable,with AUCs of 0.86 and 0.85( P=0.424). The AUCs of combination 3(3VT "poorly visualized" or any view "abnormal")and combination 4(4CV "poorly visualized" or any view "abnormal")were 0.88 and 0.86( P=0.424),all significantly higher than combination 5(LVOT "poorly visualized" or any view "abnormal",AUC=0.84,all P<0.05). Conclusions:"Poorly visualized" cardiac views in the first trimester demonstrate good diagnostic efficacy for CHD,particularly when 3VT or 4CV are affected,warranting heightened clinical vigilance for fetal cardiac anomalies.
7.The"three-early education"model for medical psychology undergraduates from the perspective of professional core competence
Lingling WANG ; Fang XIAO ; Huijie LU ; Wei LIANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(4):586-592
Objective To explore the application effectiveness of the"three-early education"model in professional quality education for medical psychology students.Methods Two groups were studied:medical psychology undergraduates of grade 2017 under conventional teaching and medical psychology undergraduates of grade 2019 under the"three-early education"model.Surveys were distributed at the end of the third academic year to evaluate their participation in research,clinical activities,and social practices,along with their satisfaction regarding the educational arrangement.Results Students from the grade 2019 cohort who received"three-early education"exhibited significantly higher rates of participation in research projects,clinical studies,and community engagement than students from the grade 2017 cohort who received traditional education(P<0.05).In comparison to the grade 2017 cohort,the grade 2019 cohort showed significantly increased satisfaction levels in curriculum design,scheduling,evaluation methods,and professional proficiency(P<0.05).Conclusion The"three-early education"model enhances the practical engagement and teaching satisfaction of medical psychology undergraduates,thereby improving their professional competence in the field of medical psychology.
8.FCN3 Can Serve as A Potential Biomarker for Prognosis and Immunotherapy of Lung Squamous Cell Carcinoma.
Wei LI ; Lingling ZU ; Song XU
Chinese Journal of Lung Cancer 2025;28(2):114-130
BACKGROUND:
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Lung squamous cell carcinoma (LUSC) is an important pathological subtype of NSCLC. The complex immune escape mechanism limits the effectiveness of immunotherapy. Ficolin-3 (FCN3) is a crucial immunomodulatory molecule that regulates immune escape by remodeling the tumor microenvironment. However, the role of FCN3 in LUSC remains unclear. This study employed bioinformatics methods to analyze LUSC samples from The Cancer Genome Atlas (TCGA) database. The aim of this study was to explore the potential biological functions and prognostic significance of FCN3 in LUSC.
METHODS:
A pan-cancer analysis characterized the expression patterns and prognostic value of FCN3 across various cancer types. Simultaneously, the expression patterns of FCN3 in LUSC samples from the TCGA database and its relationship with prognosis were analyzed. The Nomogram model and somatic mutation analysis, differential expression analysis, correlation analysis, as well as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were constructed to explore the potential mechanisms of FCN3. Additionally, immune infiltration analysis, immune escape score (TIDE), and correlation analysis of immune-related molecules were used to reveal the regulatory role of high FCN3 levels on immunity in LUSC. Furthermore, the correlation between FCN3 expression characteristics and drug sensitivity was evaluated. Finally, in vitro experiments verified the expression characteristics of FCN3 in LUSC.
RESULTS:
The expression level of FCN3 in LUSC tissues was significantly lower than that in normal tissues. Patients with high FCN3 expression in LUSC had a poorer prognosis compared to those with low expression. Different expression levels of FCN3 were associated with the abundance of immune cell infiltration and immune cell dysfunction. It was also linked to the expression of immune checkpoints, immune stimulatory molecules, major histocompatibility complex (MHC) class molecules, and chemotherapy drug sensitivity.
CONCLUSIONS
High expression of FCN3 in LUSC is associated with poor prognosis and is linked to immune cell infiltration, immune-related pathways, and immune-related molecules. FCN3 may be a potential prognostic marker and a new target for immunotherapy in LUSC.
Humans
;
Lung Neoplasms/immunology*
;
Immunotherapy
;
Biomarkers, Tumor/metabolism*
;
Prognosis
;
Lectins/metabolism*
;
Carcinoma, Squamous Cell/immunology*
;
Ficolins
;
Gene Expression Regulation, Neoplastic
9.Effect of Gynostemma pentaphyllum Alcohol Extract on Glucose and Lipid Metabolism Disorders in db/db Mice Based on Transcriptomics and Gut Microbiota
Yifei ZHU ; Lei DING ; Wei LIU ; Yahui SUN ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):80-89
ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model(DM) group, metformin(MET) group, and G. pentaphyllum alcohol extract(GP) group, with six mice in each group, based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control(NC) group. Mice in the NC and DM groups were administered deionized water (10 mL·kg-1) daily. The MET group received metformin (0.195 g·kg-1) by gavage. The GP group was treated with G. pentaphyllum alcohol extract (3.9 g·kg-1) by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention, serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure insulin (FINS), adiponectin (ADP), and tumor necrosis factor-α (TNF-α). Hematoxylin-eosin (HE) staining was used to observe liver histomorphology, periodic acid-Schiff (PAS) staining was employed to assess hepatic glycogen synthesis, and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene (Adipoq), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), glucokinase (GCK), forkhead box (Fox)O1, FoxO3, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PC). Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group, the DM group exhibited significantly elevated fasting blood glucose (P<0.01), serum AST, ALT, TC, TG, LDL-C, and HDL-C (P<0.01). FINS, homeostatic model assessment for insulin resistance (HOMA-IR), and the inflammatory cytokine TNF-α were significantly increased (P<0.01), while ADP was significantly decreased (P<0.05). Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group, along with markedly reduced glycogen synthesis. Compared with the DM group, the GP group showed significantly decreased fasting blood glucose (P<0.01), reduced serum TC, LDL-C, and HDL-C levels (P<0.05), significantly decreased serum TG and AST levels (P<0.01), significantly reduced FINS, HOMA-IR, and TNF-α levels (P<0.01), and significantly increased ADP (P<0.01). Hepatic steatosis and lipid deposition were significantly alleviated, while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α, PEPCK, G6PC, FoxO1, and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract (P<0.05, P<0.01), whereas mRNA expression of Adipoq, PPARα, GCK, and AMPK was significantly upregulated (P<0.05, P<0.01). Metagenomic analysis showed that the relative abundance of Lactobacillus, Alistipes, and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis, by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose, and by increasing the abundance of beneficial gut bacteria such as Lactobacillus, Alistipes, and Akkermansia to restore gut microbiota balance.
10.Effect of Gynostemma pentaphyllum Alcohol Extract on Glucose and Lipid Metabolism Disorders in db/db Mice Based on Transcriptomics and Gut Microbiota
Yifei ZHU ; Lei DING ; Wei LIU ; Yahui SUN ; Lingling QIN ; Lili WU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):80-89
ObjectiveTo investigate the efficacy and underlying mechanisms of Gynostemma pentaphyllum alcohol extract in improving glucose and lipid metabolism disorders in db/db mice through transcriptomics and gut microbiota analysis. MethodsEighteen db/db mice were randomly assigned to the model(DM) group, metformin(MET) group, and G. pentaphyllum alcohol extract(GP) group, with six mice in each group, based on stratification of fasting blood glucose and body weight. An additional six db/m mice were selected as the normal control(NC) group. Mice in the NC and DM groups were administered deionized water (10 mL·kg-1) daily. The MET group received metformin (0.195 g·kg-1) by gavage. The GP group was treated with G. pentaphyllum alcohol extract (3.9 g·kg-1) by gavage for six weeks. Fasting blood glucose was measured every two weeks. After six weeks of intervention, serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure insulin (FINS), adiponectin (ADP), and tumor necrosis factor-α (TNF-α). Hematoxylin-eosin (HE) staining was used to observe liver histomorphology, periodic acid-Schiff (PAS) staining was employed to assess hepatic glycogen synthesis, and Oil Red O staining was used to detect hepatic lipid deposition. Liver transcriptomic data were used to identify differentially expressed genes in the liver and conduct enrichment analysis. Real-time PCR was employed to verify the expression levels of adiponectin gene (Adipoq), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPARα), glucokinase (GCK), forkhead box (Fox)O1, FoxO3, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PC). Metagenomic sequencing was conducted to analyze changes in gut microbiota composition. ResultsCompared with the NC group, the DM group exhibited significantly elevated fasting blood glucose (P<0.01), serum AST, ALT, TC, TG, LDL-C, and HDL-C (P<0.01). FINS, homeostatic model assessment for insulin resistance (HOMA-IR), and the inflammatory cytokine TNF-α were significantly increased (P<0.01), while ADP was significantly decreased (P<0.05). Histological analysis confirmed severe hepatic steatosis and excessive lipid accumulation in the DM group, along with markedly reduced glycogen synthesis. Compared with the DM group, the GP group showed significantly decreased fasting blood glucose (P<0.01), reduced serum TC, LDL-C, and HDL-C levels (P<0.05), significantly decreased serum TG and AST levels (P<0.01), significantly reduced FINS, HOMA-IR, and TNF-α levels (P<0.01), and significantly increased ADP (P<0.01). Hepatic steatosis and lipid deposition were significantly alleviated, while glycogen synthesis was markedly enhanced. Transcriptomic differential and enrichment analyses suggested that the mechanisms by which G. pentaphyllum alcohol extract improved hepatic glucose and lipid metabolism in db/db mice may involve regulation of the AMPK and FoxO signaling pathways. Real-time PCR results confirmed that expression of PGC-1α, PEPCK, G6PC, FoxO1, and FoxO3 was significantly downregulated following treatment with G. pentaphyllum alcohol extract (P<0.05, P<0.01), whereas mRNA expression of Adipoq, PPARα, GCK, and AMPK was significantly upregulated (P<0.05, P<0.01). Metagenomic analysis showed that the relative abundance of Lactobacillus, Alistipes, and Akkermansia species was higher in the GP group than in the DM group. ConclusionG. pentaphyllum alcohol extract may improve glucose and lipid metabolism disorders in db/db mice by regulating the hepatic AMPK/PPARα pathway to suppress lipid deposition and alleviate hepatic steatosis, by inhibiting gluconeogenesis through the AMPK/PGC-1α and FoxO pathways to lower fasting blood glucose, and by increasing the abundance of beneficial gut bacteria such as Lactobacillus, Alistipes, and Akkermansia to restore gut microbiota balance.

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