Objective To analyze the literature on the"gut-liver axis"theory,and to understand the hotspots and development trends of the"gut-liver axis"theory.Methods Literatures related to the"gut-liver axis"in databases were searched from the establishment of the database to October 1,2024.A total of 292 Chinese and 1591 English articles were included.CiteSpace 6.4R1 and VOSviewer1.6.20 software were used for analysis.Results High-frequency Chinese keywords included"gut-liver axis""intestinal flora""non-alcoholic fatty liver disease"etc,10 clusters were formed.High-frequency English keywords included"gut-liver axis""gut microbiota""inflammation",etc,14 clusters were formed.Conclusion The research on the"gut-liver axis"is increasing year by year,and the direction of liver fibrosis and immunity will be the hot direction in the future.

Objective: To investigate the potential efficacy and safety of Lutai Danshen Baishao granules (LDBG) for treating female melasma associated with kidney deficiency and blood stasis patterns. Methods: A randomized, double-blind, placebo-controlled trial was conducted at the Third Central Hospital of Tianjin, China from March to December 2023. A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days. Efficacy was assessed through measures such as the total melasma area, reduced melasma area, reduction rate of melasma area, melasma color score, Melasma Area and Severity Index (MASI) score, and traditional Chinese medicine (TCM) symptom score scale. Safety assessments included routine blood and biochemical tests. Results: Participants in both groups were aged 52–63 years, with no significant differences. After the 2-month intervention, the total melasma area decreased in both groups; however, a greater reduction was observed in the test group [462.50 mm2 (12.81%) vs. 100.00 mm2 (3.11%), P < .001]. Moreover, LDBG treatment significantly reduced the MASI and melasma color scores in the test group (P < .05). The total TCM symptom evaluation score significantly decreased (test group: 6.00 vs. placebo group: 7.00, P = .001), with significant relief in symptoms such as improvement in dark lips, nails, and waist soreness in the test group, compared with that in the placebo group (P < .05). Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group (P < .05). Conclusion LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.

Objective To evaluate pulmonary vascular remodeling,right ventricular function,intestinal barrier integrity,and inflammatory factor expression in rat models of pulmonary hypertension(PH)induced by normobaric hypoxia(NH)and hypobaric hypoxia(HH).We also aimed to compare modeling method and establish an experimental basis for understanding the pathogenesis of PH and for developing appropriate treatment strategies.Methods From June 2024 to December 2024,eighteen 6-week-old male SPF Sprague-Dawley rats were assigned randomly to three groups:normobaric normoxia(Control),NH,and HH groups.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Right ventricular function was assessed using echocardiography and right ventricular hypertrophy index(RVHI).Pulmonary vascular remodeling and intestinal mucosal barrier damage were evaluated via hematoxylin/eosin staining.Colon permeability was quantified by colon ligation followed by fluorescein isothiocyanate-dextran injection.Expression levels of inflammatory factors in lung and colon tissues were analyzed by enzyme-linked immunosorbent assays.Results Right heart function assessment revealed that mPAP was significantly increased(P＜0.05),pulmonary artery acceleration time(PAAT)was shortened,and RVHI and right ventricular free wall thickness(RVFW)were significantly elevated(P＜0.05)in rats in NH and HH groups compared with Control group.Rats in NH group demonstrated a prolonged pulmonary ejection time(PET)and reduced PAAT/PET ratio compared with HH group,indicating more pronounced right heart dysfunction.Pulmonary vascular morphology demonstrated that percentage of medial area percentage(MA％)and percentage of wall thickness percentage(WT％)of pulmonary vessels were significantly higher in NH and HH groups compared with Control group(P＜0.05).Moreover,MA％was markedly increased in the NH group relative to the HH group(P＜0.05),suggesting more severe pulmonary vascular remodeling in NH group.Regarding intestinal injury,rats in NH and HH groups exhibited shorter colon length,increased mucosal damage,and significantly increased permeability compared with Control group(P＜0.05),while rats in HH group showed more prominent inflammatory cell infiltration compared with NH group,confirming intestinal mucosal barrier damage in both groups.In terms of inflammation,expression levels of interleukin(IL)6,IL1β,and IL 17a were significantly elevated in lung and colon tissues from rats in NH and HH groups compared with Control group(P＜0.05).Notably,expression levels of IL6 and IL1 β in lung tissue and IL17a in colon tissue were significantly higher in NH group compared with HH group(P＜0.05),while IL6 expression in colon tissue was relatively lower(P＜0.05),indicating local inflammation in lung and colon tissues in both groups.Conclusions There are phenotypic differences between PH rat models induced by NH and HH,with respect to pulmonary vascular remodeling,right heart function,intestinal mucosal barrier injury,and the expression of inflammatory factors in lung and intestinal tissues.These result demonstrate that air pressure contributes to the pathogenesis and progression of PH.Different air pressures may affect the development of PH via distinct mechanisms,thereby offering critical insights into the pathological changes of PH,potential therapeutic strategies to mitigate disease progression,and the elucidation of inflammatory mechanisms underlying PH based on the lung-intestine axis.

Objective To evaluate pulmonary vascular remodeling,right ventricular function,intestinal barrier integrity,and inflammatory factor expression in rat models of pulmonary hypertension(PH)induced by normobaric hypoxia(NH)and hypobaric hypoxia(HH).We also aimed to compare modeling method and establish an experimental basis for understanding the pathogenesis of PH and for developing appropriate treatment strategies.Methods From June 2024 to December 2024,eighteen 6-week-old male SPF Sprague-Dawley rats were assigned randomly to three groups:normobaric normoxia(Control),NH,and HH groups.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Right ventricular function was assessed using echocardiography and right ventricular hypertrophy index(RVHI).Pulmonary vascular remodeling and intestinal mucosal barrier damage were evaluated via hematoxylin/eosin staining.Colon permeability was quantified by colon ligation followed by fluorescein isothiocyanate-dextran injection.Expression levels of inflammatory factors in lung and colon tissues were analyzed by enzyme-linked immunosorbent assays.Results Right heart function assessment revealed that mPAP was significantly increased(P＜0.05),pulmonary artery acceleration time(PAAT)was shortened,and RVHI and right ventricular free wall thickness(RVFW)were significantly elevated(P＜0.05)in rats in NH and HH groups compared with Control group.Rats in NH group demonstrated a prolonged pulmonary ejection time(PET)and reduced PAAT/PET ratio compared with HH group,indicating more pronounced right heart dysfunction.Pulmonary vascular morphology demonstrated that percentage of medial area percentage(MA％)and percentage of wall thickness percentage(WT％)of pulmonary vessels were significantly higher in NH and HH groups compared with Control group(P＜0.05).Moreover,MA％was markedly increased in the NH group relative to the HH group(P＜0.05),suggesting more severe pulmonary vascular remodeling in NH group.Regarding intestinal injury,rats in NH and HH groups exhibited shorter colon length,increased mucosal damage,and significantly increased permeability compared with Control group(P＜0.05),while rats in HH group showed more prominent inflammatory cell infiltration compared with NH group,confirming intestinal mucosal barrier damage in both groups.In terms of inflammation,expression levels of interleukin(IL)6,IL1β,and IL 17a were significantly elevated in lung and colon tissues from rats in NH and HH groups compared with Control group(P＜0.05).Notably,expression levels of IL6 and IL1 β in lung tissue and IL17a in colon tissue were significantly higher in NH group compared with HH group(P＜0.05),while IL6 expression in colon tissue was relatively lower(P＜0.05),indicating local inflammation in lung and colon tissues in both groups.Conclusions There are phenotypic differences between PH rat models induced by NH and HH,with respect to pulmonary vascular remodeling,right heart function,intestinal mucosal barrier injury,and the expression of inflammatory factors in lung and intestinal tissues.These result demonstrate that air pressure contributes to the pathogenesis and progression of PH.Different air pressures may affect the development of PH via distinct mechanisms,thereby offering critical insights into the pathological changes of PH,potential therapeutic strategies to mitigate disease progression,and the elucidation of inflammatory mechanisms underlying PH based on the lung-intestine axis.

Objective To analyze the literature on the"gut-liver axis"theory,and to understand the hotspots and development trends of the"gut-liver axis"theory.Methods Literatures related to the"gut-liver axis"in databases were searched from the establishment of the database to October 1,2024.A total of 292 Chinese and 1591 English articles were included.CiteSpace 6.4R1 and VOSviewer1.6.20 software were used for analysis.Results High-frequency Chinese keywords included"gut-liver axis""intestinal flora""non-alcoholic fatty liver disease"etc,10 clusters were formed.High-frequency English keywords included"gut-liver axis""gut microbiota""inflammation",etc,14 clusters were formed.Conclusion The research on the"gut-liver axis"is increasing year by year,and the direction of liver fibrosis and immunity will be the hot direction in the future.

Abstract: Objective To investigate the function and molecular mechanism of LRH-1 in regulating the sensitivity of hepatocellular carcinoma (HCC) cells to oxaliplatin, providing new ideas for the treatment of liver cancer. Methods Knockdown and overexpression of LRH-1 in HCC cell lines were constructed, and the effect of LRH-1 on oxaliplatin resistance of HCC cells was explored by detecting IC50, cell proliferation, and plate colony formation assay. The transcriptional regulation of the MDR-1 gene by LRH-1 was detected through quantitative PCR. The transcriptional activation ability of LRH-1 on the MDR1 gene was evaluated by luciferase reporter assay. Results In HuH7 cells overexpressing LRH-1, the IC50 significantly increased to 18.012 μmol/L under oxaliplatin treatment, significantly higher than the 2.042 μmol/L in the HuH-7 control group, showing statistically significant differences (P<0.05). After overexpression of LRH-1 in HuH-7 cells, the cell proliferation ability was significantly increased, with a noticeable increase in MDR1 mRNA level. In HepG2 cells with knockdown LRH-1 expression, the IC50 significantly dropped to 1.012 μmol/L, significantly lower than the 6.294 μmol/L in the HepG2 control group, with statistically significant differences (P<0.05). After knockdown of LRH-1 in HepG2 cells, the cell proliferation and plate colony formation ability were significantly inhibited, with a notable decrease in MDR1 mRNA expression level. Luciferase reporter assay confirmed that LRH-1 can activate the transcriptional activity of the MDR1 promoter in a dosedependent manner, and its specific inhibitor ML-180 can significantly reduce LRH-1′s transcription activation ability on the MDR1 promoter. Conclusions LRH-1 may promote oxaliplatin resistance in hepatocellular carcinoma cells by regulating the transcriptional activity of MDR1 gene. Since its specific small molecule inhibitor has been successfully synthesized, LRH-1 can potentially become a target for the treatment of drug resistance in hepatocellular carcinoma.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Objective: To investigate the efficacy and safety of Liqingtong (LQT) granules in patients with dampness-heat hyperuricemia. Methods: A randomized, double-blind, placebo-controlled pilot trial was conducted at the 983rd Hospital of the Joint Logistic Support Force of the People's Liberation Army from March 15, 2023, to August 10, 2023. In total, 119 participants were enrolled in this trial, and participants were given either LQT granules or placebo for 60 days based on a health education. The primary outcome was serum uric acid (SUA) level, and the secondary outcome was the traditional Chinese medicine (TCM) symptom score, measured on days 0, 30, and 60. Safety indicators, including liver function, kidney function, blood routine, glucose, blood lipid, blood pressure, and heart rate were tested on days 0 and 60 of the trial. The data were analyzed using Prism 9 software, and the significance level was set at P < .05. Results: Among 119 participants, six in the LQT granule group and seven in the placebo group dropped out, and 106 participants completed clinical observation. Baseline information, including SUA levels, TCM symptom scores, and other clinical characteristics, did not differ between the groups. At the end of the trial, compared with baseline values, the SUA levels in the LQT granule group decreased (P < .001), and no significant change was observed in the placebo group (P = .422); compared with the placebo group, the SUA levels decreased in the LQT granule group (P = .001). Compared with baseline values, the total TCM symptom scores in the LQT granule group decreased (P < .001), with no change in the placebo group (P = .136). Safety indicators did not differ significantly between the two groups. Conclusion The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.

Objective:To identify the influencing factors of postoperative nausea and vomiting (PONV) in the patients undergoing egg retrieval with general anesthesia for in vitro fertilization-embryo transfer (IVF-ET).Methods:This was a case-control study. Medical records from IVF-ET patients undergoing egg retrieval with general anesthesia in the Center for Reproductive Medicine in our hospital from November to December 2020 were retrospectively collected, 52 patients with PONV were identified (group PONV), and 252 patients without PONV were selected as control group (group C). Univariate analysis was performed on the suspicious influencing factors, and the factors with statistically significant differences were included in the logistic regression analysis model to identify the influencing factors of PONV.Results:Compared with group C, statistically significant differences were found in the number of eggs, anesthesia time, and the proportion of PONV history and/or motion sickness history in group PONV ( P<0.05). The results of multivariate logistic regression analysis showed that a large number of eggs, long anesthesia time, and a high proportion of PONV history and/or motion sickness history were independent risk factors for PONV. Conclusions:A large number of eggs, long anesthesia time, and a high proportion of PONV history and/or motion sickness history are independent risk factors for PONV in IVF-ET patients undergoing egg retrieval with general anesthesia.