OBJECTIVES: Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury. METHODS: An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis. RESULTS: Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01). CONCLUSIONS Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals ; Hepatocytes/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Reperfusion Injury/prevention & control* ; Apoptosis/drug effects* ; Reactive Oxygen Species/metabolism* ; MAP Kinase Signaling System/drug effects* ; Cell Survival/drug effects* ; Cell Hypoxia ; Cells, Cultured

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.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective:To summarize the characteristics of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants and evaluate the efficacy and safety of transcatheter PDA closure (TCPC).Methods:This was a retrospective study including five VLBW preterm infants who were diagnosed with hsPDA by echocardiography at Women and Children's Hospital, Qingdao University from January to December 2024 and underwent transcatheter closure after pharmacological therapy failure. Follow-up assessments were conducted at 6 months after operation to evaluate PDA closure status, survival outcomes, and the occurrence of complications. Descriptive statistical analysis was used to summarize the demographic characteristics and clinical data.Results:The cohort comprised three males and two females. The median gestational age was 28 (24-29) weeks, and the median birth weight was 1 000 (670-1 220) g. The median age and birth weight at surgery were 25 (13-36) d and 1 200 (810-1 400) g, respectively. The PDA diameter was 3.8 (2.3-4.1) mm. PDA closure was successfully achieved in all five infants using the Amplatzer Piccolo? occlude, with no major procedure-related complications. All patients were weaned from mechanical ventilation and discharged. At 6-month follow-up, all five infants survived with no residual shunt, left pulmonary artery stenosis, or aortic coarctation on echocardiography.Conclusions:TCPC is feasible and safe for VLBW preterm infants when pharmacological therapy is ineffective or contraindicated. Larger cohorts and extended follow-up are needed to assess long-term outcomes and potential complications.

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

Objective:To summarize the characteristics of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants and evaluate the efficacy and safety of transcatheter PDA closure (TCPC).Methods:This was a retrospective study including five VLBW preterm infants who were diagnosed with hsPDA by echocardiography at Women and Children's Hospital, Qingdao University from January to December 2024 and underwent transcatheter closure after pharmacological therapy failure. Follow-up assessments were conducted at 6 months after operation to evaluate PDA closure status, survival outcomes, and the occurrence of complications. Descriptive statistical analysis was used to summarize the demographic characteristics and clinical data.Results:The cohort comprised three males and two females. The median gestational age was 28 (24-29) weeks, and the median birth weight was 1 000 (670-1 220) g. The median age and birth weight at surgery were 25 (13-36) d and 1 200 (810-1 400) g, respectively. The PDA diameter was 3.8 (2.3-4.1) mm. PDA closure was successfully achieved in all five infants using the Amplatzer Piccolo? occlude, with no major procedure-related complications. All patients were weaned from mechanical ventilation and discharged. At 6-month follow-up, all five infants survived with no residual shunt, left pulmonary artery stenosis, or aortic coarctation on echocardiography.Conclusions:TCPC is feasible and safe for VLBW preterm infants when pharmacological therapy is ineffective or contraindicated. Larger cohorts and extended follow-up are needed to assess long-term outcomes and potential complications.

As the major part of mesencephalic locomotion region, pedunculopontine tegmental nucleus (PPN) participates in motor initiation, rhythmic and speed regulation. In addition, PPN is regarded as a novel deep brain stimulation target for patients with Parkinson′s disease due to its dramatic effect on the gait disturbance and postural instability. However, PPN also has an important role in muscle tone control and dystonia. This review is aimed at summarizing the involvement of PPN in dystonia, providing fundamental for targeting PPN for treatment of dystonia in the future.