Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

Objective: To investigate the current status and trends of depressive symptoms among middle school and college students in Hunan Province, and to explore the primary related factors of depressive symptoms, so as to provide a scientific basis for strengthening mental health among students. Methods: A total of 279 382 students in Hunan Province were selected through a stratified cluster random sampling method from 2021 to 2023. National Survey Questionnaire on Common Diseases and Health Influencing Factors among Students was adopted for the survey, and the Center for Epidemiological Studies Depression Scale was used to assess their depressive symptoms. The χ 2 test and trend χ 2 test were used to analyze depressive symptoms prevalence and trends, and multivariable Logistic regression was used to analyze the related factors of depressive symptoms. Results: The prevalence of depressive symptoms among students in Hunan Province from 2021 to 2023 were 19.66%, 20.17% and 21.47%, respectively, showing an upward trend ( χ 2 trend =9.07, P <0.01). In addition, the results of the multivariable Logistic regression analysis showed that students with healthy diet ( OR=0.43, 95%CI =0.40-0.45), adequate sleep ( OR=0.88, 95%CI =0.86-0.90), and acceptable screen time ( OR=0.61, 95%CI =0.60-0.62) had lower risks in depressive symptoms detection, while students with smoking ( OR= 1.95, 95%CI =1.88-2.02), secondhand smoke exposure ( OR=1.33, 95%CI =1.30-1.36) and Internet addiction ( OR= 4.19 , 95%CI =4.05-4.34) had higher risks in depressive symptoms detection, with differences in the degree of association among different genders, educational stages and urban rural groups ( OR=0.40-6.04, Z =-12.69-11.98) ( P <0.05). Conclusions There is an increasing trend of depressive symptoms among middle school and college students in Hunan Province from 2021 to 2023.Targeted depression prevention measures should be taken for students with different demographic characteristics to promote their mental health.

ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the health check-up population， and to perform stratified management of patients with the low， medium， and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019， and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI， the MAFLD group was further divided into lean MAFLD group （125 individuals with BMI<24 kg/m²） and non-lean MAFLD group （943 individuals with BMI≥24 kg/m²）. Indicators including demographic data， past history， laboratory examination， and liver ultrasound were compared between groups. Fibrosis-4 （FIB-4） score， NAFLD fibrosis score （NFS）， aspartate aminotransferase-to-platelet ratio index （APRI）， and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-9.758， P<0.05）， proportion of male patients （χ²=137.555， P<0.05）， and levels of body weight （Z=-27.987， P<0.05）， BMI （Z=-32.714， P<0.05）， waist circumference （Z=-31.805， P<0.05）， hip circumference （Z=-26.342， P<0.05）， waist-hip ratio （Z=-28.554， P<0.05）， alanine aminotransferase （ALT） （Z=-25.820， P<0.05）， aspartate aminotransferase （AST） （Z=-16.894， P<0.05）， gamma-glutamyl transpeptidase （GGT） （Z=-25.069， P<0.05）， alkaline phosphatase （Z=-12.533， P<0.05）， triglyceride （Z=-27.559）， total cholesterol （Z=-7.833， P<0.05）， low-density lipoprotein cholesterol （LDL-C） （Z=-8.222， P<0.05）， and uric acid （UA） （Z=-20.024， P<0.05）， as well as a significantly higher proportion of patients with metabolic syndrome （MetS） （χ²=578.220， P<0.05）， significantly higher prevalence rates of hypertension （χ²=241.694， P<0.05）， type 2 diabetes （χ²=796.484， P<0.05）， and dyslipidemia （χ²=369.843， P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （HDL-C） （Z=23.153， P<0.001）. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=1.45， 95% confidence interval ［CI］： 1.203‍ ‍—‍ ‍1.737）， ALT （OR=1.05， 95%CI： 1.046‍ ‍—‍ ‍1.062）， LDL-C （OR=1.23， 95%CI： 1.102‍ ‍—‍ ‍1.373）， and comorbidity with MetS （OR=5.97， 95%CI： 4.876‍ ‍—‍ ‍7.316） were independently associated with MAFLD. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.736， P<0.05） and HDL-C （Z=2.679， P<0.05） and significant reductions in the proportion of male patients （χ²=28.970， P<0.05）， body weight （Z=-14.230， P<0.05）， BMI （Z=-18.188， P<0.05）， waist circumference （Z=-13.451， P<0.05）， hip circumference （Z=-13.317， P<0.05）， ALT （Z=-4.519， P<0.05）， AST （Z=-2.258， P<0.05）， GGT （Z=-4.592， P<0.05）， UA （Z=-4.415， P<0.05）， the proportion of patients with moderate or severe fatty liver disease or MetS （χ²=42.564， P<0.05）， and the prevalence rates of hypertension （χ²=12.057， P<0.05） and type 2 diabetes （χ²=3.174， P<0.05）. Among the patients with MAFLD， 10 patients （0.9%） had an FIB-4 score of >2.67， 4 patients （0.4%） had an NFS score of >0.676， 8 patients （0.7%） had an APRI of >1， and 551 patients （51.6%） had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing， but with a relatively low number of patients with a high risk of advanced fibrosis， and such patients need to be referred to specialized hospitals for liver diseases.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Traditional Chinese medicine(TCM) resources are an important foundation for the theory and practice of TCM. Rare and endangered TCM, as a significant component of these resources, plays an essential role. Conducting research on substitutes for rare and endangered TCM resources is of great significance for alleviating resource shortages, promoting the sustainable utilization of TCM, and advancing TCM modernization. This paper reviews the conservation achievements of rare and endangered Chinese medicinal materials in China and organizes the substitution methods for these materials. Currently, the main substitution approaches include introduction and domestication, tissue culture, varietal replacement, and artificial synthesis. Furthermore, this paper proposes the following approaches for researching the application scenarios of rare and endangered medicinal materials, i.e., tracing the historical context of their use to clarify foundational principles; verifying disease classifications to strengthen the clinical application scenarios of these materials; analyzing the evolution patterns of prescription formulations to strengthen the mining of the compatibility application scenarios of rare and endangered medicinal materials; scientifically evaluating to strengthen the application scenario research and development of endangered Chinese patent medicine industry. These efforts aim to promote the scientific substitution and sustainable utilization of rare and endangered medicinal materials and their substitutes.
Drugs, Chinese Herbal/chemistry* ; Humans ; Medicine, Chinese Traditional ; China ; Plants, Medicinal/growth & development* ; Endangered Species ; Conservation of Natural Resources ; Animals

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry