This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts ( n = 101) and those with low sperm motility or concentration ( n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 ( MAP2K2 ), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.
Male ; Humans ; Spermatozoa/metabolism* ; RNA, Transfer/genetics* ; Sperm Motility/genetics* ; Adult ; Semen Analysis ; Sexual Abstinence/physiology* ; Sperm Count ; DNA Fragmentation

Objective To evaluate the efficacy and safety of rivaroxaban in elderly patients with atrial fibrillation.Methods The cases datas of 236 elderly patients with atrial fibrillation hospitalized in Minzu Hospital of Guangxi Zhuang Autonomous Region from July 2022 to September 2023 were retrospectively analyzed.According to the use of anticoagulant drugs,they were divided into rivaroxaban group(148 cases)and warfarin group(88 cases).New thrombosis,bleeding events and all-cause death during hospitalization were compared between two groups.Logistic regression and multi-factor Cox regression analysis were used to investigate the influencing factors of new thrombus,hemorrhage and all-cause death.Results The proportion of antiplatelet drugs and platelet count in rivaroxaban group were significantly higher than those in warfarin group,and thrombin time,prothrombin time and international standardized ratio were significantly lower than those in warfarin group(P＜0.05).Before and after adjusting for confounders,there were no significant differences in the risk of new thrombosis,bleeding events and all-cause death between two groups(P＞0.05).Multivariate Cox regression analysis showed that combined use of non steroidal antiinflammatory drug and low-dose rivaroxaban were risk factors for death in elderly patients with atrial fibrillation(P＜0.05).Conclusion The efficacy and safety of rivaroxaban in elderly patients with atrial fibrillation are not inferior to warfarin.

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

Objective To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone(ROT)-induced Parkinson's disease(PD)model mouse.Methods SPF C57BL/6 mice were randomly divided into 6 groups,including control group,solvent control group,ROT model group,ACT001 5 mg/kg group(ROT+ACT001-5),ACT001 20 mg/kg group(ROT+ACT001-20),and levodopa(L-dopa)positive control group(ROT+L-dopa),with 9 mice in each group.The control group received an equivalent amount of intraperitoneal injection of saline,the solvent control group received an equivalent amount of rotenone solvent without rotenone,the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone.Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001,while the positive control group received levodopa intraperitoneally for 15 consecutive days.Behavioral changes in mice were assessed using open field,rotarod,pole-climbing,and balance beam tests.Immunofluorescence(IF)assay to detect the expression of tyrosine hydroxylase(TH)neurons,content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain;Real-time PCR was employed to measure the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in the substantia nigra of the mouse brain.Western blotting was used to measure the protein levels of TH,nuclear factor-κB(NF-κB)p65,NF-κB inhibitor α(IκBα),and phosphorylated IκBα(p-IκBα)in the substantia nigra of the mouse brain.Results Compared to the control group and the solvent control group,the rotenone-induced PD model group exhibited motor impairments in behavioral tests,a decrease in the number of TH positive neurons in the substantia nigra(P＜0.0001),decreased levels of TH-positive fibers in the striatum,activation of midbrain substantia microglia,and elevated levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 expression.ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice,increased the number of TH-positive neurons in the substantia nigra,increased levels of TH-positive fibers in the striatum,inhibition of microglial cell activation in the midbrain substantia nigra,and elevated the protein expression levels of IκBα while reducing the levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 in the substantia nigra(P＜0.05).At a dose of 5 mg/kg,ACT001 significantly improved behavioral impairments in rotenone-induced PD mice,reduced the loss of dopaminergic neurons,and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the suppression of inflammation.In summary,the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain,increased the number of TH-positive neurons,and augmented the population of dopaminergic neurons in the substantia nigra,exerting a protective effect on neurons.Conclusion ACT001 significantly improves behavioral deficits in ROT-induced PD mice,ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum,inhibits the activation of nigrostriatal microglia in the midbrain,and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Objective:To analyze the factors influencing the prognoses of stroke survivors with pseudobulbar palsy (PBP) dysphagia and construct a prediction model.Methods:Data on two hundred and fifty-one stroke survivors with PBP dysphagia were collected and analyzed retrospectively. The subjects were divided into a good prognosis group ( n=164) and a poor prognosis group ( n=87) according to the results of Kubota water swallowing tests administered at discharge. Their clinical data were analyzed using univariate correlation analysis, and the statistically significant independent variables found were further analyzed using multivariate logistic regression to obtain the important predictors of prognosis. R software was then used to assemble the useful factors into a nomogram prediction model. The area under the receiver operating characteristics (ROC) curve was employed to verify the model′s predictive power. Results:According to the univariate correlation analysis, significant differences were found between the two groups′ average National Institutes of Health Stroke Scale (NIHSS) scores, mouth opening grades and ages. The multivariate logistic regression analysis showed that NIHSS score, mouth opening grade and age could be useful and independent predictors of poor prognosis. The ROC curve analysis showed that the area under the curve for the nomogram model was 0.727, with a sensitivity of 59.8% and a specificity of 81.6%, suggesting that the model had good predictive power and was properly calibrated.Conclusions:NIHSS score, mouth opening grade and age are independent predictors of prognosis for stroke patients with PBP dysphagia. The nomogram model constructed in this study is of great value in developing a prognosis for such patients, which is helpful in the prevention and treatment of post-stroke dysphagia.

Objective:To analyze the factors influencing the prognoses of stroke survivors with pseudobulbar palsy (PBP) dysphagia and construct a prediction model.Methods:Data on two hundred and fifty-one stroke survivors with PBP dysphagia were collected and analyzed retrospectively. The subjects were divided into a good prognosis group ( n=164) and a poor prognosis group ( n=87) according to the results of Kubota water swallowing tests administered at discharge. Their clinical data were analyzed using univariate correlation analysis, and the statistically significant independent variables found were further analyzed using multivariate logistic regression to obtain the important predictors of prognosis. R software was then used to assemble the useful factors into a nomogram prediction model. The area under the receiver operating characteristics (ROC) curve was employed to verify the model′s predictive power. Results:According to the univariate correlation analysis, significant differences were found between the two groups′ average National Institutes of Health Stroke Scale (NIHSS) scores, mouth opening grades and ages. The multivariate logistic regression analysis showed that NIHSS score, mouth opening grade and age could be useful and independent predictors of poor prognosis. The ROC curve analysis showed that the area under the curve for the nomogram model was 0.727, with a sensitivity of 59.8% and a specificity of 81.6%, suggesting that the model had good predictive power and was properly calibrated.Conclusions:NIHSS score, mouth opening grade and age are independent predictors of prognosis for stroke patients with PBP dysphagia. The nomogram model constructed in this study is of great value in developing a prognosis for such patients, which is helpful in the prevention and treatment of post-stroke dysphagia.

Objective To evaluate the efficacy and safety of rivaroxaban in elderly patients with atrial fibrillation.Methods The cases datas of 236 elderly patients with atrial fibrillation hospitalized in Minzu Hospital of Guangxi Zhuang Autonomous Region from July 2022 to September 2023 were retrospectively analyzed.According to the use of anticoagulant drugs,they were divided into rivaroxaban group(148 cases)and warfarin group(88 cases).New thrombosis,bleeding events and all-cause death during hospitalization were compared between two groups.Logistic regression and multi-factor Cox regression analysis were used to investigate the influencing factors of new thrombus,hemorrhage and all-cause death.Results The proportion of antiplatelet drugs and platelet count in rivaroxaban group were significantly higher than those in warfarin group,and thrombin time,prothrombin time and international standardized ratio were significantly lower than those in warfarin group(P＜0.05).Before and after adjusting for confounders,there were no significant differences in the risk of new thrombosis,bleeding events and all-cause death between two groups(P＞0.05).Multivariate Cox regression analysis showed that combined use of non steroidal antiinflammatory drug and low-dose rivaroxaban were risk factors for death in elderly patients with atrial fibrillation(P＜0.05).Conclusion The efficacy and safety of rivaroxaban in elderly patients with atrial fibrillation are not inferior to warfarin.