Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl₄)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl₄-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

OBJECTIVES: To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center. METHODS: We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software. RESULTS: In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (P=0.022), 0.79±0.11 g/cm² in the femoral neck (P<0.001), and 0.88±0.11 g/cm² in the total hip (P<0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023). CONCLUSIONS Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.
Humans ; Bone Density ; Absorptiometry, Photon ; Male ; Female ; Retrospective Studies ; Osteoporosis/diagnostic imaging* ; Adult ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging* ; China/epidemiology* ; Femur Neck/diagnostic imaging* ; Aged ; Beijing/epidemiology* ; Young Adult

Heavy metals are common occupational hazards that can enter the human body through ingestion, skin contact, and inhalation, damaging various systems including the nervous system and causing a serious disease burden. Numerous studies have shown that heavy metal-induced neurotoxicity is closely linked to intestinal flora imbalance, with exposure to heavy metals leading to a reduction in the diversity of intestinal flora and a decrease in beneficial intestinal bacteria. Due to their few adverse reactions and significant health-regulating effects, probiotics and their formulations are widely used. Supplementing probiotics can alleviate heavy metal-induced neurotoxicity by modulating intestinal flora and their metabolites, reducing inflammation and oxidative stress, and adsorbing heavy metal ions to facilitate their excretion. This article takes four common heavy metals, namely lead, mercury, cadmium and manganese, as examples to review the role of intestinal flora imbalance in the neurotoxicity of heavy metals and the mechanism and application of probiotic intervention treatment, aiming to provide new ideas for the prevention and treatment of heavy metal neurotoxicity and explore the potential mechanism and application value of probiotic intervention.

Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl4)-treated mice and patients with cirrhosis.Deletion of Pafah 1b3 significantly attenuated CCl4-induced fibrosis,hepatic stellate cell(HSC)activation,and acti-vation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-β receptor 1(TβR1),which subsequently decreases TβR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl4-induced fibrosis in mice.Furthermore,Pafah 1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafahl b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin Ⅶ(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,sup-pressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Heavy metals are common occupational hazards that can enter the human body through ingestion, skin contact, and inhalation, damaging various systems including the nervous system and causing a serious disease burden. Numerous studies have shown that heavy metal-induced neurotoxicity is closely linked to intestinal flora imbalance, with exposure to heavy metals leading to a reduction in the diversity of intestinal flora and a decrease in beneficial intestinal bacteria. Due to their few adverse reactions and significant health-regulating effects, probiotics and their formulations are widely used. Supplementing probiotics can alleviate heavy metal-induced neurotoxicity by modulating intestinal flora and their metabolites, reducing inflammation and oxidative stress, and adsorbing heavy metal ions to facilitate their excretion. This article takes four common heavy metals, namely lead, mercury, cadmium and manganese, as examples to review the role of intestinal flora imbalance in the neurotoxicity of heavy metals and the mechanism and application of probiotic intervention treatment, aiming to provide new ideas for the prevention and treatment of heavy metal neurotoxicity and explore the potential mechanism and application value of probiotic intervention.

Objective To observe the clinical efficacy of Guishao Liujunzi Decoction combined with traditional Chinese medicine(TCM)mouthrinse in the treatment of helicobacter pylori(Hp)associated gastritis,and its effect on the Hp conversion rate.Methods Eighty patients with Hp-related gastritis were selected and randomly divided into the control group(standard quadruple therapy)and the treatment group(standard quadruple therapy combined with Guishao Liujunzi Decoction and TCM mouthrinse),with 40 patients in each group.The clinical efficacy,TCM syndrome scores,and Hp conversion rate of the two groups were observed.Results The total effective rate of the treatment group(95%)was higher than that of the control group(72.5%)(P<0.05).The Hp conversion rate in the treatment group(90%)was higher than that in the control group(72.5%)(P<0.05).After treatment,the main symptom scores and total scores of the two groups decreased compared to before treatment,and the treatment group was lower than the control group(P<0.05).Conclusion The combination of modified Guishao Liujunzi decoction and TCM mouthrinse in the treatment of Hp-related gastritis can significantly improve clinical efficacy and Hp negative conversion rate compared to conventional treatment.

OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

Objective:To discusses the variations of 7Be, 137Cs and 210Pb activity concentrations in the air in Beijing from March 16, 2021 to March 31, 2023, and their correlation with temperature, precipitation, relative humidity, barometric pressure, PM10 (only limited to 137Cs) and other meteorological parameters. Methods:A total of 60 aerosol samples were collected using the HRHA01-SFS1000/A ultra-large flowair sampler in the automatic radiation monitoring station. The activity concentrations of 7Be, 137Cs and 210Pb in the aerosol samples were measured by GMX-60 low background anti-Compton high purity germanium gamma spectrometer. Pearson correlation coefficient was used to show the correlation of the relevant parameters. Results:The seasonal mean values of 7Be activity concentration were spring 4.31 mBq/m 3, summer 3.53 mBq/m 3, autumn 3.09 mBq/m 3 and winter 2.45 mBq/m 3, respectively, ranging from 1.17 to 7.79 mBq/m 3, with the overall mean of (3.36±1.33) mBq/m 3. The activity concentration of 137Cs ranged from 0.39 to 8.49 μBq/m 3, with an average of (0.59±1.47) μBq/m 3. The average activity concentrations of 210Pb were spring 0.53 mBq/m 3, summer 0.44 mBq/m 3, autumn 0.72 mBq/m 3 and winter 0.75 mBq/m 3, respectively, ranging from 0.21 to 1.36 mBq/m 3, with an average of (0.56±0.26) mBq/m 3. The activity concentration of 7Be was correlated with temperature and pressure ( r=0.38, -0.40), the activity concentration of 137Cs was correlated with precipitation ( r=-0.41), and the activity concentration of 210Pb was correlated with temperature and pressure ( r=-0.31, 0.37). The variation of 137Cs activity concentration in the air showed an obvious seasonal pattern, and the peak value generally appears in spring of each year (March to May), which was related to the frequent spring dust in Beijing. The activity concentration of 210Pb in the air was affected by coal combustion heating in winter, and has a peak value during November to March. Conclusions:The activity concentrations of 7Be, 137Cs and 210Pb in the air in Beijing are within the normal range, showing a seasonal trend.