1.Roles and mechanism of bile acids and gut microbiota in primary biliary cholangitis
Mengyao WU ; Jiayin PAN ; Rong DING ; Jinyu LI ; Wenlin TAI
Journal of Clinical Hepatology 2026;42(4):957-964
Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by the injury of small intrahepatic bile ducts, and at present, the pathogenesis of PBC remains unclear. Recent studies have shown that bile acid metabolism disorder and gut microbiota imbalance play a key role in the development and progression of PBC, and they form a complex and dynamic interaction network via the “gut-liver axis” and regulate core physiopathological processes such as immune response, metabolic homeostasis, and inflammatory response in a synergistic manner. This article systematically elaborates on the abnormal features of bile acid metabolism and gut microbiota in PBC, discusses their synergistic mechanisms in PBC, and then proposes a combined strategy of targeting bile acid receptors and modulating gut microbiota, in order to overcome the limitations of current treatment modalities and provide new insights and directions for the clinical management of PBC.
2.Effect of Zaogong Erteng decoction on endometritis and TLR4-mediated signaling pathways
Yaqiu LI ; Qingcan GUAN ; Lixin WANG ; Nan KANG ; Huiling LIU ; Feng YAN ; Jinyu ZHANG ; Xuenan WANG ; Xiaoyan PAN
Chinese Journal of Reproduction and Contraception 2025;45(3):255-266
Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.
3.Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers
Jinyu WU ; Jiajun WEI ; Shugang GUO ; Huixia XIONG ; Yong WANG ; Hongyue KONG ; Liuquan JIANG ; Baolong PAN ; Gaisheng LIU ; Fan YANG ; Jisheng NIE ; Jin YANG
Journal of Environmental and Occupational Medicine 2025;42(3):325-333
Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.
4.Research progress in platelet blood group detection technology
Jinyu SHEN ; Gangqing PAN ; Shujuan CHEN ; Xuerong SUN ; Jie RUAN
Chinese Journal of Laboratory Medicine 2025;48(8):1101-1106
With the advancement of transfusion medicine and the widespread use of platelet-related preparations, platelet transfusion has become a critical therapeutic intervention in clinics. To enhance the safety and efficacy of platelet transfusion, platelet blood group typing has been increasingly implemented in clinical practice, accompanied by the emergence of novel testing technologies and methodologies, such as flow cytometric immuno-bead array analysis, microtiter plate-based immobilized recombinant single antigen enzyme-linked immunosorbent assay and third-generation sequencing. Significant progress has been made in platelet blood group detection, including improvements in serological testing methods, integration and optimization of multi-platform detection technologies, and the development of high-throughput molecular genotyping techniques. The advancement in platelet blood group detection technology has significantly enhanced detection precision and clinical applicability, providing an important support for transfusion safety, managing platelet-related diseases, and developing antiplatelet drugs.
5.Effect of Zaogong Erteng decoction on endometritis and TLR4-mediated signaling pathways
Yaqiu LI ; Qingcan GUAN ; Lixin WANG ; Nan KANG ; Huiling LIU ; Feng YAN ; Jinyu ZHANG ; Xuenan WANG ; Xiaoyan PAN
Chinese Journal of Reproduction and Contraception 2025;45(3):255-266
Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.
6.Research progress in platelet blood group detection technology
Jinyu SHEN ; Gangqing PAN ; Shujuan CHEN ; Xuerong SUN ; Jie RUAN
Chinese Journal of Laboratory Medicine 2025;48(8):1101-1106
With the advancement of transfusion medicine and the widespread use of platelet-related preparations, platelet transfusion has become a critical therapeutic intervention in clinics. To enhance the safety and efficacy of platelet transfusion, platelet blood group typing has been increasingly implemented in clinical practice, accompanied by the emergence of novel testing technologies and methodologies, such as flow cytometric immuno-bead array analysis, microtiter plate-based immobilized recombinant single antigen enzyme-linked immunosorbent assay and third-generation sequencing. Significant progress has been made in platelet blood group detection, including improvements in serological testing methods, integration and optimization of multi-platform detection technologies, and the development of high-throughput molecular genotyping techniques. The advancement in platelet blood group detection technology has significantly enhanced detection precision and clinical applicability, providing an important support for transfusion safety, managing platelet-related diseases, and developing antiplatelet drugs.
7.Scoping review of research on mobile app-based weight management in patients with breast cancer
Huoling PAN ; Xinyu LI ; Jinyu ZHANG
Chinese Journal of Health Management 2024;18(4):295-301
Objective:To conduct a scoping review of mobile app-based weight management studies in patients with breast cancer.Methods:The studies related to weight management in patients with breast cancer based on mobile apps in nine Chinese and English databases, including PubMed, Embase, Cochrane, EBSCOhost, Scopus, Sinomed, VIP database, Wanfang Database and China National Knowledge Infrastructure (CNKI), were systematically searched with the terms of “breast cancer” “weight management” “mobile health” and “weight”. The search period was from the establishment of the databases to July 29, 2022. The literature was screened, and data were extracted and summarized based on the Omaha system.Results:A total of 7 literatures were included, all were in English. The mobile apps included in the studies varied with sample sizes, ranging from 10 to 356 cases. Six of the studies involved breast cancer patients who had completed surgery or chemoradiotherapy, and none of the studies involved breast cancer patients undergoing chemotherapy. Forms of intervention included exercise or diet alone and a combination of both exercise and diet, and most studies had shown good intervention effects. According to the Omaha intervention system, the most commonly extracted intervention component was self-management advice, which was offered to patients in six studies, and none of the intervention studies included intervention components related to case management.Conclusions:An intervention for weight management based on mobile apps in breast cancer patients has a good effect and is feasible. However, there is a limited number of related studies, and there is a lack of interventional research specifically targeting patients during chemotherapy, which still needs to be actively carried out.
8.The impact of oral multidimensional carbohydrates on early postoperative recovery in patients undergoing unilateral biportal endoscopy spine surgery
Guoyu NI ; Tianyu BAI ; Feng JIN ; Hai MENG ; Yingkai ZHANG ; Jisheng LIN ; Jinyu GUO ; Jinxia PAN ; Yong YANG ; Qi FEI
International Journal of Surgery 2024;51(12):808-813
Objective:To explore the impact of different preoperative fluid supplementation methods (oral multidimensional carbohydrates and conventional fluid supplementation) on early postoperative recovery and pain management in patients undergoing unilateral biportal endoscopic (UBE) spine surgery.Methods:A retrospective cohort study was conducted to analyze the data of 386 patients who underwent UBE lumbar spine surgery under general anesthesia in the two courtyards of Beijing Friendship Hospital Affiliated to Capital Medical University from May 2023 to April 2024. All patients were divided into oral multidimensional carbohydrates ( "Outfast" supplementation, composed mainly of water, sugars, salts, and vitamins) group (referred to as oral "Outfast" group, 189 patients) and conventional fluid supplementation group (197 patients) according to the type of fluid replenishment. Patients in the oral "Outfast" group were given one oral dose in the morning of the first surgery, and another oral infusion before 10∶00 in the morning of the next surgery or afternoon surgery. Patients in the conventional fluid supplementation group received intravenous infusion in the morning of the first surgery, and were given intravenous infusion of glucose and sodium chloride injection in the morning of the next surgery or afternoon surgery. The two groups were compared for the proportion of patients receiving preoperative intravenous fluids on the day of surgery, intraoperative and postoperative fluid volumes, average daily fluid volumes over the first three postoperative days, time to first postoperative ambulation, time to first bowel movement, post-anesthesia care unit (PACU) stay duration, 4-hour and 24-hour postoperative visual analog scale (VAS) pain scores, incidence of anesthesia-related adverse reactions, and incidence of severe gastrointestinal adverse reactions. The measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for inter-group comparison. The measurement data of skewed distribution were expressed as M ( Q1, Q3) and rank sum test was used for inter-group comparison. Count data was presented in terms of examples and percentages, and a chi-square test was used for comparison between two groups. Results:In the oral "Outfast" group, 8 patients (4.2%) received preoperative intravenous fluids on the day of surgery, compared to 136 patients (69.0%) in the conventional fluid supplementation group, showing a significant difference ( P<0.001). The postoperative fluid volumes, average daily fluid volumes over the first three postoperative days, and shorter time to first ambulation in the oral multidimensional carbohydrates group were 700.0(600.0, 1 100.0) mL, 200.0(200.0, 300.0) mL, and 6.0(6.0, 11.0) h, respectively. The conventional fluid supplementation group was 1 100.0(700.0, 1 200.0) mL, 600.0(500.0, 700.0) mL, and 12.0(6.0, 19.0) h, respectively. The oral "Outfast" group was lower than the conventional fluid supplementation group ( P<0.001).There were no significant differences between the two groups in intraoperative fluid volumes, time to first bowel movement, PACU stay duration, 4-hour and 24-hour VAS pain scores, incidence of anesthesia-related adverse reactions, or incidence of severe gastrointestinal adverse reactions ( P>0.05). Conclusions:Preoperative oral multidimensional carbohydrates supplementation effectively reduces the amount of preoperative and postoperative intravenous fluid required, shortens the time to first ambulation. Preoperative oral multidimensional carbohydrates is safe and does not adversely impact gastrointestinal reactions or pain management in the postoperative period.
9.LCN2 inhibits lipopolysaccharide-mediated M1 polarization of mouse BV2 microglia through P38 MAPK-PGC1α-PPARγ pathway
Yimo FENG ; Jun LAI ; Bo LIN ; Jinyu PAN ; Yanghao ZHOU ; Hanjian DU
Chinese Journal of Pathophysiology 2024;40(12):2278-2285
AIM:To investigate the role of lipocalin 2(LCN2)in lipopolysaccharide(LPS)-induced microg-lia polarization in mice and to elucidate the potential mechanisms involving the P38 mitogen-activated protein kinase(MAPK)pathway.METHODS:BV2 microglia were treated with LPS to induce M1 polarization,and short hairpin RNA(shRNA)and exogenous LCN2 protein were used to silence or overexpress LCN2 in BV2 cells.BV2 microglia were cul-tured in vitro and divided into the following groups:control,LPS(100 μg/L),LPS+sh-NC,LPS+sh-LCN2,and LPS+LCN2(1 mg/L).Flow cytometry was used to detect the number of CD16/32+and CD206+T cells.Western blot and RT-qP-CR were employed to measure the protein and mRNA levels of P38 MAPK,PGC-1α,and PPARγ to assess the effects of LCN2 on LPS-induced BV2 cell polarization and the P38 MAPK pathway.Additionally,the P38 MAPK pathway inhibitor SB203580 was used to treat LPS or LCN2-induced cells.The cells were categorized into control,LPS,LPS+LCN2(1 mg/L),LPS+SB203580(50 nmol/L),and LPS+LCN2+SB203580 groups.ELISA was used to measure inflammatory factor levels,Western blot was used to detect M1/M2 marker proteins,and Western blot and RT-qPCR were used to analyze pro-tein and mRNA expressions in the P38 MAPK pathway.RESULTS:LPS significantly increased LCN2 expression in BV2 cells(P<0.05)and induced M1 polarization(P<0.01).Silencing LCN2 reduced LCN2 expression and M2 polarization in LPS-induced BV2 cells(P<0.01),increased M1 polarization(P<0.01),and inhibited activation of the P38 MAPK-PGC-1α-PPARγ pathway(P<0.05).Conversely,exogenous addition of LCN2 promoted M2 polarization in LPS-induced BV2 cells and activated the P38 MAPK pathway(P<0.05).The use of a P38 MAPK pathway inhibitor further confirmed that LCN2 modulates LPS-induced microglia polarization through the P38 MAPK pathway.CONCLUSION:LCN2 inhibits LPS-mediated M1 polarization of BV2 microglia by activating the P38 MAPK pathway,thereby playing a protective role in neuroinflammatory responses.
10.LCN2 inhibits lipopolysaccharide-mediated M1 polarization of mouse BV2 microglia through P38 MAPK-PGC1α-PPARγ pathway
Yimo FENG ; Jun LAI ; Bo LIN ; Jinyu PAN ; Yanghao ZHOU ; Hanjian DU
Chinese Journal of Pathophysiology 2024;40(12):2278-2285
AIM:To investigate the role of lipocalin 2(LCN2)in lipopolysaccharide(LPS)-induced microg-lia polarization in mice and to elucidate the potential mechanisms involving the P38 mitogen-activated protein kinase(MAPK)pathway.METHODS:BV2 microglia were treated with LPS to induce M1 polarization,and short hairpin RNA(shRNA)and exogenous LCN2 protein were used to silence or overexpress LCN2 in BV2 cells.BV2 microglia were cul-tured in vitro and divided into the following groups:control,LPS(100 μg/L),LPS+sh-NC,LPS+sh-LCN2,and LPS+LCN2(1 mg/L).Flow cytometry was used to detect the number of CD16/32+and CD206+T cells.Western blot and RT-qP-CR were employed to measure the protein and mRNA levels of P38 MAPK,PGC-1α,and PPARγ to assess the effects of LCN2 on LPS-induced BV2 cell polarization and the P38 MAPK pathway.Additionally,the P38 MAPK pathway inhibitor SB203580 was used to treat LPS or LCN2-induced cells.The cells were categorized into control,LPS,LPS+LCN2(1 mg/L),LPS+SB203580(50 nmol/L),and LPS+LCN2+SB203580 groups.ELISA was used to measure inflammatory factor levels,Western blot was used to detect M1/M2 marker proteins,and Western blot and RT-qPCR were used to analyze pro-tein and mRNA expressions in the P38 MAPK pathway.RESULTS:LPS significantly increased LCN2 expression in BV2 cells(P<0.05)and induced M1 polarization(P<0.01).Silencing LCN2 reduced LCN2 expression and M2 polarization in LPS-induced BV2 cells(P<0.01),increased M1 polarization(P<0.01),and inhibited activation of the P38 MAPK-PGC-1α-PPARγ pathway(P<0.05).Conversely,exogenous addition of LCN2 promoted M2 polarization in LPS-induced BV2 cells and activated the P38 MAPK pathway(P<0.05).The use of a P38 MAPK pathway inhibitor further confirmed that LCN2 modulates LPS-induced microglia polarization through the P38 MAPK pathway.CONCLUSION:LCN2 inhibits LPS-mediated M1 polarization of BV2 microglia by activating the P38 MAPK pathway,thereby playing a protective role in neuroinflammatory responses.

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