Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Objective:To analyze the factors associated with long-term survival after radical resection of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),and to construct random forest and Cox regression models,to evaluate the two models.Methods:A total of 368 patients with HBV-infected HCC who underwent radical resection were selected retrospectively.These patients were categorized as having a good prognosis(n=266)or a poor prognosis(n=102)based on their survival and mortality status.Univariate and Cox regression analysis were used to identify fac-tors that predict poor prognosis in HCC patients after surgery,and Cox regression and random forest prediction models were constructed and evaluated.Results:There were significant differences in smoking history,Child-Pugh classifica-tion,cirrhosis,microvascular invasion,TNM staging,tumor capsule integrity,platelet-to-lymphocyte ratio(PLR),regular antiviral therapy,HBV-DNA load,alpha-fetoprotein(AFP),neutrophil-to-lymphocyte ratio(NLR),systemic immune in-flammatory index(SII),and albumin-to-globulin ratio(AGR)between the two groups(P<0.05);Cox regression showed that cirrhosis,microvascular invasion,regular antiviral treatment,HBV-DNA load,NLR,PLR,SII,and AGR were related factors that negatively affected the prognosis of patients with HBV-infected HCC after surgery(P<0.05),with an AUC of 0.870 for predicting prognosis;the importance ranking obtained by the random forest model was HBV-DNA load,cirrho-sis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII,with an AUC of 0.926 for predicting prog-nosis;the AUC predicted by the random forest model was greater than that predicted by the Cox regression model(Z=2.411,P=0.016).Conclusion:HBV-DNA load,cirrhosis,regular antiviral therapy,microvascular invasion,NLR,PLR,AGR,and SII are factors that affect the poor prognosis of patients with HBV-related HCC after surgery.The random for-est prediction model constructed based on these factors has high predictive value and is superior to the Cox regression prediction model.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

AIM To investigate the effects of Polygonum cuspidatum and polydatin on lipid deposition in adipose tissue of high-fat diet-induced obese mice.METHODS Forty male C57BL/6J mice were randomly assigned to either a control group(10 mice)fed standard chow or a diet-induced obesity(DIO)group(30 mice)fed a high-fat diet for 8 weeks.The successful mouse models were randomly assigned to the model group,the polydatin group(250 mg/kg)and the P.cuspidatum group(4.5 g/kg),with 8 mice in each group,to resume their high-fat diet during the following 8 weeks corresponding drug administration by gavage.Weekly body weight measurements were recorded for all mice.Serum TG,TC and LDL levels were quantified post-treatment.Histopathological assessment of adipose tissue was performed using HE staining.The mRNA expressions of AMPK,SREBP-1c and FAS in adipose tissue were analyzed by RT-qPCR.The protein expressions of p-AMPK,SREBP-1c and FAS in adipose tissue was detected by Western blot.RESULTS Compared to the control group,the model group displayed significantly higher body weight,inguinal fat weight and epididymal fat weight(P＜0.05);elevated serum TG,TC and LDL levels(P＜0.05);markedly enlarged volumes of inguinal and epididymal adipocytes(P＜0.01);reduced p-AMPK protein expression in inguinal adipose tissue(P＜0.01);and upregulated mRNA and protein expressions of SREBP-1c and FAS(P＜0.05,P＜0.01).Compared to the model group,both the P.cuspidatum group and polygonin group exhibited significantly reduced body weight and inguinal fat weight(P＜0.05);decreased serum TG and TC levels(P＜0.05);reduced inguinal adipocyte size(P＜0.01);elevated p-AMPK protein expression in inguinal adipose tissue(P＜0.01);and downregulated mRNA and protein expressions of SREBP-1c and FAS(P＜0.05,P＜0.01).CONCLUSION P.cuspidatum and polydatin significantly increases p-AMPK expression while decreasing SREBP-1c and FAS levels in adipose tissue.This regulatory effect likely contributes to reduction of body weight in obese mice through suppression of lipogenesis.

Objective To explore the regulatory effect of amylin on the feeding behavior of mice through the ERK pathway of paraventricular nucleus of the hypothalamus(PVN).Methods A total of 54 C57BL/6J mice were randomly divided into multiple groups for experiments.First,immunofluorescence was used to detect the distribution of ERK and calcitonin receptor(CTR)neurons in the brains of 4 mice.A chemical lesion model of PVN neurons was established,and 16 mice were divided into four groups(4 mice per group):control(Ctrl)group,ibotenic acid(IBO)-lesioned group,amylin group,and amylin+IBO group.The number of ERK-positive neurons in the PVN region and food intake were then measured.Subsequently,16 mice were divided into four groups(4 mice per group),Ctrl group,amylin group,ERK antagonist U0126 group,and amylin+U0126 group.The expression level of the immediate early gene c-fos in the PVN was detected by Real-time PCR.Immunofluorescence was used to detect the distribution of p-ERK positive neurons in the brains of 4 saline-treated mice and 4 amylin-treated mice.Finally,18 mice were randomly divided into three groups(6 mice per group)through intracerebroventricular injection,Ctrl group,amylin group,and amylin+receptor antagonist AC 187 group.Then,triple immunofluorescence was used to detect the co-expression of p-ERK,neuronal nitric oxide synthase(nNOS),and CTR-immunopositive neurons in the PVN region,and food intake within 3 hours after treatment was recorded simultaneously.Results ERK-positive neurons were mainly distributed in the suprachiasmatic nucleus(SCN),arcuate nucleus(ARC),and locus coeruleus(LC),while ERK and CTR co-expressing positive neurons were specifically enriched in the PVN(P=0.0012).Lesion of PVN neurons led to a decrease in the number of ERK-positive neurons(P＜0.001)and blocked the anorectic effect of amylin(P＜0.001).Amylin activated the expression of the c-fos gene in the PVN region(P＜0.05),and this effect was inhibited by U0126(P＜0.05).After intracerebroventricular injection of amylin,the number of triple-positive neurons for p-ERK,nNOS,and CTR in the PVN increased(P＜0.05).Addition of AC 187 blocked the activation effect of amylin(P＜0.01)and reversed the anorectic effect of amylin(1 h,P=0.2218;2 h,P=0.2218;3 h,P=0.6974).Conclusion P-ERK neurons in the PVN regulate feeding behavior through an amylin receptor-dependent ERK signaling pathway.

As an innovative dosage form, traditional Chinese medicine(TCM) dry powder inhalers have emerged as a focal point in the research and development of new preparations due to its high efficiency, safety, and bioavailability. This paper systematically reviewed the relevant literature and patents associated with TCM dry powder inhalers to analyze the origins and the current research and development status. Furthermore, this paper probed into the research and development ideas of TCM dry powder inhalers regarding clinical positioning, prescription screening, and druggability. Additionally, the paper thoroughly analyzed the technical barriers in druggability studies and elaborated on corresponding research techniques and coping measures. Furthermore, it emphasized the need for improved regulations and policies governing TCM dry powder inhalers, advocated for strengthened oversight, and called for the establishment of a scientific quality evaluation system. Measures such as promoting production-education-research collaboration, enhancing personnel training, and fostering international exchanges were proposed to provide a scientific and systematic reference for the future research, development, and application of TCM dry powder inhalers, thereby facilitating the rapid modernization of TCM.
Humans ; Dry Powder Inhalers/trends* ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/instrumentation* ; Administration, Inhalation

Based on the regulation of mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway, this study investigated the effect of Jianpi Qinghua Formula on the mitochondrial fatty acid β-oxidation pathway in the livers of mice with metabolic-associated fatty liver disease(MAFLD) induced by a high-fat diet. MAFLD mice were fed a high-fat diet to establish the model, and after successful modeling, the mice were divided into the model group, the Jianpi Qinghua Formula group, and the metformin group, with an additional control group. Each group was treated with the corresponding drug or an equivalent volume of saline via gavage. Body mass and food intake were measured regularly during the experiment. At the end of the experiment, blood lipid levels and liver function-related indices were measured, liver pathological changes were observed, and protein expression levels of PGC1α, PPARα, PPARγ, and CPT1A were detected by Western blot. The results showed that, with no difference in food intake, compared to the model group, the body mass of the Jianpi Qinghua Formula group and the metformin group was reduced, liver weight and liver index decreased, and levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol(LDL-C) were lowered. Additionally, a decrease in alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was observed. Hematoxylin and eosin(HE) staining revealed reduced pathological damage to hepatocytes, while oil red O staining showed improvement in fatty infiltration. The liver disease activity score decreased, and transmission electron microscopy revealed improvement in mitochondrial swelling and restoration of internal cristae. Western blot analysis indicated that Jianpi Qinghua Formula significantly increased the expression of PGC1α, PPARα, and CPT1A proteins in the liver and reduced the expression of PPARγ. These results suggest that the Jianpi Qinghua Formula improves mitochondrial function, promotes fatty acid oxidation, and alleviates the pathological changes of MAFLD. In conclusion, Jianpi Qinghua Formula can improve MAFLD by mediating mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway.
Animals ; PPAR alpha/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Carnitine O-Palmitoyltransferase/genetics* ; Male ; Liver/metabolism* ; Fatty Liver/genetics* ; Humans ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects*

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*