ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Endometriosis （EMT） is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea， pelvic mass， and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease， which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However， the pathogenesis of EMT is still not completely clear， and the disease has a long course. Therefore， developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine （TCM）， while the underlying mechanism remains in exploration. Programmed cell death （PCD） is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis， which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM， which regulates PCD via multiple pathways， routes， targets， and mechanisms. However， the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes （apoptosis， pyroptosis， autophagy， ferroptosis， and cuproptosis）， with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

BACKGROUND AND OBJECTIVE: Social anxiety arising from intensive social media usage (SMU) among adolescents and youth has gained extensive attention in recent years due to its negative influence on mental health and academic performance. In spite of that, there is a dearth regarding the etiology of SMU-related social anxiety. This study aims to further clarify the influence of introversion personality on SMU-related social anxiety and the mechanism underlying such an association and provide a new perspective for developing effective intervention strategies for the highly prevailing SMU-related anxiety among Chinese college students. METHODS: A cohort of 979 college students (266 males and 713 females) aged 20.90 ± 1.91 years was enrolled in this cross-sectional study. Four measures including the "extroversion" domain of Eysenck Personality Questionnaire Revised, Short Scale (EPQ-R-S E), Interaction Anxiousness Scale (IAS), Mobile Phone Addiction Index (MPAI), and Social Anxiety Scale for Social Media Users (SAS-SMU) were used to evaluate the influence of introversion personality on SMU-related social anxiety that was potentially mediated sequentially by interaction anxiousness and mobile phone addiction. Hayes PROCESS was used for correlation and mediation analysis. RESULTS: Interaction anxiousness (indirect effect = -1.331, 95% CI : -1.559 - -1.122) partially mediated the association between introversion personality and SMU-related social anxiety. Besides, a sequential mediation of interaction anxiousness and mobile phone addiction in the link between introversion personality and SMU-related social anxiety was revealed (indirect effect = -0.308, 95% CI : -0.404 - -0.220). No significant mediating effect was found with mobile phone addiction in the association between introversion personality and SMU-related social anxiety. CONCLUSION: Targeting interaction anxiousness and mobile phone addiction may represent an efficient strategy alleviating SMU-related social anxiety among Chinese college students with introversion personality.
Humans ; Male ; Female ; Social Media ; Students/psychology* ; Anxiety/psychology* ; Young Adult ; Cross-Sectional Studies ; Universities ; Behavior, Addictive/psychology* ; Cell Phone ; Adolescent ; Introversion, Psychological ; China ; Surveys and Questionnaires ; Internet Addiction Disorder/psychology*