Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.

Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.

Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

Background and objective Non-small cell lung cancer (NSCLC) presents the highest morbidity and mortality among malignant tumors worldwide. hTe overall effective rate of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is 30% to 40%, and PFS (progression-free sruvival) is 12 months. However, EGFR-TKI resistance is typical in clinical observations, and this phenomenon signiifcantly affects tumor suppression. To overcome this resistance, a new prognostic factor associated with lung cancer drug resistance should be discovered. This study investigated the rela-tionship between the inhibitor of differentiation 1 (ID1) and non-small cell lung cancer EGFR-TKI resistancein vivo andin vitro to determine any statistical signiifcance and discuss the underlying mechanism.Methods Western blot and qRT-PCR were used to quantify the expression of ID1 in lung cancer. IHC was used to detect the expression of ID1 in pathological tissues (lung cancer tissues and adjacent tissues). MTT was used to detect cell proliferation, in which the cells were treated with geiftinib atfer being transfected by ID1 slow virus vector. Lung cancer cells were inoculated in nude mice until the tu-mor diameter grew to certain measurement. Geiftinib treatment was started, and the tumor volume was estimated.Results ID1 was highly expressed in NSCLC (P<0.05). Both ID1 expression and drug resistance of EGFR-TKI in NSCLC were positively correlated (P<0.05). hTe treatment group with geiftinib showed obviously less expression than the control group. Conclusion ID1 is highly expressed in NSCLC. ID1 expression was positively related to drug resistance of EGFR-TKI in NSCLC. Geiftinib can be used to effectively treat NSCLC, and the mechanism may be associated with an increased level of STAT3 phosphorylation.

OBJECTIVETo explore the feasibility of genetic algorithm (GA) on multiple objective blending technology for extractions of Cortex Fraxini.

METHODAccording to that the optimization objective was the combination of fingerprint similarity and the root-mean-square error of multiple key constituents, a new multiple objective optimization model of 10 batches extractions of Cortex Fraxini was built. The blending coefficient was obtained by genetic algorithm. The quality of 10 batches extractions of Cortex Fraxini that after blending was evaluated with the finger print similarity and root-mean-square error as indexes.

RESULTThe quality of 10 batches extractions of Cortex Fraxini that after blending was well improved. Comparing with the fingerprint of the control sample, the similarity was up, but the degree of variation is down. The relative deviation of the key constituents was less than 10%.

CONCLUSIONIt is proved that genetic algorithm works well on multiple objective blending technology for extractions of Cortex Fraxini. This method can be a reference to control the quality of extractions of Cortex Fraxini. Genetic algorithm in blending technology for extractions of Chinese medicines is advisable.

Algorithms ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Medicine, Chinese Traditional ; standards ; Plants, Medicinal ; chemistry ; genetics ; Quality Control