BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Bovine coronavirus(BCoV)can cause diarrhea in calves,as well as respiratory diseases,and lead to the death of calves in severe cases,resulting in great economic losses to the cattle pro-duction.BCoV is highly prevalent and widely spread.So far in China there is no independently de-veloped vaccine against BCoV on the market.In this study,the most conserved N gene of BCoV was first selected to construct a prokaryotic expression vector,and the N protein was expressed and purified;subsequently,BALB/c mice were immunized with BCoV N protein combined with Freund's adjuvant,and the antibody potency,the proportion of splenic T-lymphocyte subpopulation and the cytokine release of the immunized mice were detected by ELISA and flow cytometry.The results showed that a soluble BCoV N protein about 55 kDa in size was successfully obtained.The ELISA test showed that the antibody potency of serum IgG and IgA was 1∶51 200 and 1∶3 200,respectively,in mice immunized with BCoV N protein combined with Freund's adjuvant.The flow cytometry test showed that the percentage of CD4+/CD8+T-lymphocytc subsets was extremely higher in the immunized mice(P＜0.01),and the release of TNF-α was significantly higher(P＜0.05),producing a cellular immune response biased towards the Th1 type in comparison with that in control mice.It is indicated that the soluble expression of BCoV N protein can be successfully a-chieved by the prokaryotic expression system,and the obtained BCoV N protein presents good im-munogenicity which induces strong humoral,mucosal and cellular immune responses in the immu-nized mice.Our study provides an important technical support for the development of a safe and ef-fective BCoV subunit vaccine.

Gastric cancer(GC)is one of the most common malignancies worldwide.In our country,the majority of patients are diagnosed with GC at alocally advanced stage.Fortunately,clinical studies have demonstrated that minimally invasive radical gastrectomy,particularly laparoscopic surgery,is just as effective as traditional open surgery in terms of both short-and long-term outcomes.Consequently,minim-ally invasive surgery has become the primary surgical approach for patients with locally advanced gastric cancer(LAGC).Advancements in surgical techniques and technologies are enabling even more precise and minimally invasive approaches to GC surgery.Based on recent do-mestic and international studies,this study aimed to review and elaborate on the development of minimally invasive surgery for LAGC.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:Postdoctoral researchers in Chinese universities commonly face a high risk of mental health issues,such as depression,yet the underlying causes and mechanisms remain unclear.This study aims to explore the influence of childhood socioeconomic status(SES)on depression among postdoctoral researchers and the mediating roles of current subjective SES and perceived stress in this process. Methods:An online survey was conducted among postdoctoral researchers at a university.The survey included a general information questionnaire,the Childhood Socioeconomic Status Scale,the Subjective Socioeconomic Status Scale,the Perceived Stress Scale,and the Patient Health Questionnaire.A total of 505 valid responses were collected.Pearson correlation analysis was used to analyze the data,and the PROCESS macro was employed for chain mediation analysis. Results:Childhood SES was significantly positively correlated with current subjective SES(P<0.05)and significantly negatively correlated with postdoctoral tenure,perceived stress,and depression(all P<0.05).Current subjective SES was significantly negatively correlated with perceived stress and depression(both P<0.05),while perceived stress was significantly positively correlated with depression(P<0.05).The chain mediation effect of childhood SES → current subjective SES → perceived stress → depression was significant(P<0.05). Conclusion:Childhood socioeconomic status can influence depression among postdoctoral researchers through the mediating roles of current subjective socioeconomic status and perceived stress.These findings provide a target for the prevention and intervention of depression in postdoctoral populations and offer a reference for the development of mental health promotion strategies for young university faculty.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.

Bovine coronavirus(BCoV)can cause diarrhea in calves,as well as respiratory diseases,and lead to the death of calves in severe cases,resulting in great economic losses to the cattle pro-duction.BCoV is highly prevalent and widely spread.So far in China there is no independently de-veloped vaccine against BCoV on the market.In this study,the most conserved N gene of BCoV was first selected to construct a prokaryotic expression vector,and the N protein was expressed and purified;subsequently,BALB/c mice were immunized with BCoV N protein combined with Freund's adjuvant,and the antibody potency,the proportion of splenic T-lymphocyte subpopulation and the cytokine release of the immunized mice were detected by ELISA and flow cytometry.The results showed that a soluble BCoV N protein about 55 kDa in size was successfully obtained.The ELISA test showed that the antibody potency of serum IgG and IgA was 1∶51 200 and 1∶3 200,respectively,in mice immunized with BCoV N protein combined with Freund's adjuvant.The flow cytometry test showed that the percentage of CD4+/CD8+T-lymphocytc subsets was extremely higher in the immunized mice(P＜0.01),and the release of TNF-α was significantly higher(P＜0.05),producing a cellular immune response biased towards the Th1 type in comparison with that in control mice.It is indicated that the soluble expression of BCoV N protein can be successfully a-chieved by the prokaryotic expression system,and the obtained BCoV N protein presents good im-munogenicity which induces strong humoral,mucosal and cellular immune responses in the immu-nized mice.Our study provides an important technical support for the development of a safe and ef-fective BCoV subunit vaccine.

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.