Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective To analyze the temporal changing trend of postoperative pneumonia(POP)monitoring data in a tertiary first-class cancer hospital in Fujian Province from 2018 to 2023,and provide reference for the effective-ness of implementation of healthcare-associated infection(HAI)prevention and control measures.Methods The temporal changing trend of POP monitoring data of cancer patients in this hospital from 2018 to 2023 was analyzed by Joinpoint regression model,and the average annual percentage change(AAPC)was calculated.Results From 2018 to 2023,the POP incidences of all cancer patients and patients with different tumors in this hospital were as follows:3.46％in all cancer patients,4.77％,18.16％,11.50％,4.66％,0.85％,3.74％,and 0.46％in pa-tients with lung cancer,esophageal cancer,gastric cancer,intestinal cancer,gynecological tumors,hepatobiliary-pancreatic tumor,as well as head and neck tumors,respectively.From 2018 to 2023,the POP incidence of all can-cer patients in the hospital decreased from 5.47％to 1.73％,and POP incidences of patients with lung cancer,gas-tric cancer,and intestinal cancer decreased from 12.23％,14.93％,and 4.40％to 2.60％,3.73％,and 2.09％,respectively.Joinpoint regression model analysis showed that from 2018 to 2023,the AAPC of POP incidence of all cancer patients in the hospital was-19.78％,and the AAPCs of patients with lung cancer,gastric cancer,and in-testinal cancer were-23.69％,-27.30％,and-19.40％,respectively.The incidences of POP in all cancer pa-tients,as well as patients with lung cancer,gastric cancer,and intestinal cancer all showed downward trends,and the differences were all statistically significant(all P＜0.05).According to age,the AAPCs of the ≤60 and＞60 year old groups were-22.02％and-20.48％,respectively,both groups showed statistically significant difference in trends(both P＜0.05).In terms of gender,the AAPCs of the male and female groups were-16.56％and-28.35％,respectively,both groups showed statistically significant difference in trends(both P＜0.05).From 2018 to 2023,Klebsiella pneumoniae showed a significant upward trend in the constituent of POP pathogens in cancer patients,with an AAPC of 6.92％,and the difference was statistically significant(P＜0.05).Conclusion The incidences of POP in some cancer patients in the hospital present significant downward trends,indicating that HAI infection prevention and control measures are effective,but it is still necessary to strengthen the meticulous management of the whole perioperative process.

Objective::To investigate the correlation between maternal serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and gestational duration in pregnant women with pulmonary hypertension (PH).Methods::The study included pregnant individuals with PH stemming from mitral valve stenosis and mitral valve regurgitation (post-capillary PH) or pulmonary arterial hypertension (pre-capillary PH) who were admitted to Guangdong Provincial People’s Hospital between January 1, 2014 and December 31, 2020. In this retrospective cohort study, maternal serum NT-proBNP levels during pregnancy, along with other clinical data, were obtained from structured electronic medical records. These data included gestational age at delivery, echocardiographic parameters, laboratory findings, gestational duration, delivery mode, and other relevant clinical variables. Univariate and multivariate regression analyses were conducted to assess the association between NT-proBNP levels and gestational duration. Adjustments were made for potential confounding factors, and curve fitting and threshold effect analysis were employed to identify tangent points. Furthermore, stratified analyses were performed based on tricuspid regurgitation velocity, maternal age, and parity.Results::A total of 64 patients with post-capillary PH and 74 patients with pre-capillary PH were included in this study. Among patients with post-capillary PH, the results of multivariate regression analysis indicated a significant association between maternal NT-proBNP levels and gestational duration (β = -0.03, 95% confidence interval (CI) -0.05 to 0.00, P = 0.02). The fitted curve demonstrated a negative correlation between maternal NT-proBNP levels and gestational duration, with a significant break point at 379.9 ng/L ( P < 0.05). In the post-capillary PH group, the stratified analysis revealed a regression coefficient of -0.05 (95% CI:-0.06 to -0.04, P = 0.001) in patients with a tricuspid regurgitation velocity >340 mm/s. For patients >35 years old, the regression coefficient was -0.03 (95% CI -0.06 to -0.01, P = 0.02). In multiparous women, the regression coefficient was -0.03 (95% CI-0.06 to 0.00, P = 0.03). Conclusion::In pregnant women with pulmonary hypertension, maternal NT-proBNP levels are associated with gestational duration, particularly with an increased risk of preterm labor.

Objective::To investigate the correlation between maternal serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and gestational duration in pregnant women with pulmonary hypertension (PH).Methods::The study included pregnant individuals with PH stemming from mitral valve stenosis and mitral valve regurgitation (post-capillary PH) or pulmonary arterial hypertension (pre-capillary PH) who were admitted to Guangdong Provincial People’s Hospital between January 1, 2014 and December 31, 2020. In this retrospective cohort study, maternal serum NT-proBNP levels during pregnancy, along with other clinical data, were obtained from structured electronic medical records. These data included gestational age at delivery, echocardiographic parameters, laboratory findings, gestational duration, delivery mode, and other relevant clinical variables. Univariate and multivariate regression analyses were conducted to assess the association between NT-proBNP levels and gestational duration. Adjustments were made for potential confounding factors, and curve fitting and threshold effect analysis were employed to identify tangent points. Furthermore, stratified analyses were performed based on tricuspid regurgitation velocity, maternal age, and parity.Results::A total of 64 patients with post-capillary PH and 74 patients with pre-capillary PH were included in this study. Among patients with post-capillary PH, the results of multivariate regression analysis indicated a significant association between maternal NT-proBNP levels and gestational duration (β = -0.03, 95% confidence interval (CI) -0.05 to 0.00, P = 0.02). The fitted curve demonstrated a negative correlation between maternal NT-proBNP levels and gestational duration, with a significant break point at 379.9 ng/L ( P < 0.05). In the post-capillary PH group, the stratified analysis revealed a regression coefficient of -0.05 (95% CI:-0.06 to -0.04, P = 0.001) in patients with a tricuspid regurgitation velocity >340 mm/s. For patients >35 years old, the regression coefficient was -0.03 (95% CI -0.06 to -0.01, P = 0.02). In multiparous women, the regression coefficient was -0.03 (95% CI-0.06 to 0.00, P = 0.03). Conclusion::In pregnant women with pulmonary hypertension, maternal NT-proBNP levels are associated with gestational duration, particularly with an increased risk of preterm labor.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective To analyze the temporal changing trend of postoperative pneumonia(POP)monitoring data in a tertiary first-class cancer hospital in Fujian Province from 2018 to 2023,and provide reference for the effective-ness of implementation of healthcare-associated infection(HAI)prevention and control measures.Methods The temporal changing trend of POP monitoring data of cancer patients in this hospital from 2018 to 2023 was analyzed by Joinpoint regression model,and the average annual percentage change(AAPC)was calculated.Results From 2018 to 2023,the POP incidences of all cancer patients and patients with different tumors in this hospital were as follows:3.46％in all cancer patients,4.77％,18.16％,11.50％,4.66％,0.85％,3.74％,and 0.46％in pa-tients with lung cancer,esophageal cancer,gastric cancer,intestinal cancer,gynecological tumors,hepatobiliary-pancreatic tumor,as well as head and neck tumors,respectively.From 2018 to 2023,the POP incidence of all can-cer patients in the hospital decreased from 5.47％to 1.73％,and POP incidences of patients with lung cancer,gas-tric cancer,and intestinal cancer decreased from 12.23％,14.93％,and 4.40％to 2.60％,3.73％,and 2.09％,respectively.Joinpoint regression model analysis showed that from 2018 to 2023,the AAPC of POP incidence of all cancer patients in the hospital was-19.78％,and the AAPCs of patients with lung cancer,gastric cancer,and in-testinal cancer were-23.69％,-27.30％,and-19.40％,respectively.The incidences of POP in all cancer pa-tients,as well as patients with lung cancer,gastric cancer,and intestinal cancer all showed downward trends,and the differences were all statistically significant(all P＜0.05).According to age,the AAPCs of the ≤60 and＞60 year old groups were-22.02％and-20.48％,respectively,both groups showed statistically significant difference in trends(both P＜0.05).In terms of gender,the AAPCs of the male and female groups were-16.56％and-28.35％,respectively,both groups showed statistically significant difference in trends(both P＜0.05).From 2018 to 2023,Klebsiella pneumoniae showed a significant upward trend in the constituent of POP pathogens in cancer patients,with an AAPC of 6.92％,and the difference was statistically significant(P＜0.05).Conclusion The incidences of POP in some cancer patients in the hospital present significant downward trends,indicating that HAI infection prevention and control measures are effective,but it is still necessary to strengthen the meticulous management of the whole perioperative process.

Objective:To explore the effect of pentraxin 3 (PTX3) on memory improvement and Aβ expression in Alzheimer's disease (AD) model mice.Methods:(1) Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 group and control group were stereotactically injected 4 μL 0.5 g/L PTX3 or same dose of phosphate buffered saline (PBS); Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the brain hemisphere. (2) Twenty-five 3-month-old 5×FAD mice were randomly divided into model group, 2 μg/kg PTX3 group, 4 μg/kg PTX3 group, 8 μg/kg PTX3 group, and 16 μg/kg PTX3 group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 groups were intranasally injected 2, 4, 8, and 16 μg/kg PTX3, respectively; those in the model group and control group were intranasally injected same dose of PBS; injection was given once every 96 h for a total of 7 times. Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the hippocampus. Results:(1) Compared with the model group, the PTX3 group had significantly shorter platform latency, higher percentage of exploration time and higher percentage of spontaneous alternations ( P<0.05). Compared with those in model group ([63.38±21.42] pg/mL, [29.77±6.11] pg/mL), the concentrations of Aβ 40 and Aβ 42 in the brain tissues of PTX3 group ([15.87±2.11] pg/mL, [16.55±1.95] pg/mL) were statistically lower ( P<0.05). (2) Compared with the model group, the 16 μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time ( P<0.05); compared with the model group, the 2 μg/kg PTX3 group and 16 μg/kg PTX3 group had significantly higher percentage of spontaneous alternations ( P<0.05). The contents of Aβ 40 and Aβ 42 in the hippocampus of 8 μg/kg PTX3 group and 16 μg/kg PTX3 group were statistically lower compared with those in the model group ( P<0.05). Conclusion:PTX3 may attenuate cognitive deficits and decrease Aβ expression in the brain or hippocampus tissues of 5×FAD mice with AD.