OBJECTIVE: To explore the improvement effect of electroacupuncture (EA) based on Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) on cognitive impairment in mice with Parkinson's disease (PD), and to explore its regulatory mechanisms on the kinesin family member 5A (KIF5A)/mitochondrial Rho GTPase 1 (Miro1) pathway and mitophagy in prefrontal cortical neurons. METHODS: A total of 70 male C57BL/6J mice of clean grade were randomly divided into a normal group (12 mice), a sham operation group (12 mice), and a model pre-screening group (46 mice). Unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle was adopted to establish the PD model in the model pre-screening group. Twenty-four mice after successful modeling were randomly selected and divided into a model group and an EA group, 12 mice in each one. In the EA group, acupuncture was applied at "Shuigou" (GV26) and bilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6), ipsilateral "Sanyinjiao" (SP6) and "Neiguan" (PC6) were connected to EA respectively, with disperse-dense wave, 5 Hz/20 Hz in frequency, 0.5 mA in current intensity, 20 min a time, 6 times a week for 30 days. Cognitive function was assessed by Y-maze and Morris water maze tests; morphology of prefrontal cortex was observed by H.E. staining; reactive oxygen species (ROS) level in prefrontal cortex was detected by fluorescence probe method; mitochondrial morphology and autophagosome ultrastructure were observed by transmission electron microscopy; the mRNA expression of tyrosine hydroxylase (TH) was detected by quantitative real-time PCR; the protein expression of TH, KIF5A, Miro1, p62, Parkin and PTEN induced kinase 1 (PINK1) was detected by Western blot. RESULTS: Compared with the sham operation group, both the model group and the EA group exhibited increased rotation number of per minute (P<0.001). Compared with the sham operation group, in the model group, the novel arm exploration time of Y-maze test was shortened (P<0.001), the escape latency of Morris water maze test was prolonged (P<0.05) and the platform crossing number of Morris water maze test was reduced (P<0.01); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was increased (P<0.001), and mitochondrial autophagosomes could be observed; in the prefrontal cortex, the relative expression of ROS was increased (P<0.001), the protein and mRNA expression of TH was decreased (P<0.001), the protein expression of Miro1, PINK1, Parkin was increased (P<0.001, P<0.01), the protein expression of KIF5A and p62 was decreased (P<0.001). Compared with the model group, in the EA group, the novel arm exploration time of Y-maze test was prolonged (P<0.01), the escape latency of Morris water maze test was shortened (P<0.05) and the platform crossing number of Morris water maze test was increased (P<0.05); in the prefrontal cortex, the number of cellular vacuole and neurons with karyopyknosis was decreased (P<0.001), and the number of mitochondrial autophagosomes reduced and the mitochondrial morphology was improved; in the prefrontal cortex, the relative expression of ROS was decreased (P<0.01), the protein and mRNA expression of TH was increased (P<0.001, P<0.01), the protein expression of Miro1, PINK1, Parkin was decreased (P<0.001, P<0.01, P<0.05), the protein expression of KIF5A and p62 was increased (P<0.01, P<0.05). CONCLUSION Xingnao Kaiqiao electroacupuncture effectively alleviates cognitive impairment and damage of neuronal function in PD mice, its mechanism may be related to the regulation of KIF5A/Miro1 pathway, hence reducing the mitophagy in prefrontal cortical neurons.
Animals ; Electroacupuncture ; Male ; Mice ; Parkinson Disease/physiopathology* ; Cognitive Dysfunction/psychology* ; Kinesins/genetics* ; Humans ; Mitophagy ; Mice, Inbred C57BL ; rho GTP-Binding Proteins/genetics* ; Mitochondria/genetics* ; Prefrontal Cortex/metabolism*

Objective To investigate the mechanism by which Biejiajian Pill(BJJP)regulates ferroptosis in hepatocellular carcinoma(HCC)cells through the p62/Keap1/NRF2 pathway and to provide an experimental basis for its application in the prevention and treatment of HCC.Methods Huh7 HCC cells were divided into a normal control group,a BJJP drug serum group,an erastin(a ferroptosis inducer)group,a BJJP drug serum+erastin group,and BJJP drug serum+ferrostatin-1(Fer-1)(a ferroptosis inhibitor)group.BJJP drug serum was prepared with animals treated with BJJP and CCK-8 assay was performed to determine the optimal concentration and duration of BJJP intervention.The levels of intracellular iron(Fe),reduced glutathione(GSH),lipid peroxides(MDA),and reactive oxygen species(ROS)were measured.Western blot was performed to determine the expression levels of FTH1,GPX4,xCT,SLC40A1,Keapl,p62,and NRF2.JC-1 staining was performed to measure mitochondrial membrane potential,and cell immunofluorescence was performed to determine the expression of p62 and Keap1.Results According to the CCK-8 assay results,the cell inhibition rate was highest when BJJP was administered at a high dose of 2.2 g/kg(P＜0.001).Furthermore,the inhibition rate of Huh7 cells was highest when Huh7 cells were treated with high-dose BJJP drug serum for 48 h.Therefore,the serum concentration of high-dose BJJP and 48 h were selected as the treatment dose and duration for the subsequent experiment.Compared with the control group,the BJJP drug serum group,the erastin group,and the BJJP drug serum+erastin group showed increased iron content,decreased GSH content,increased MDA levels,increased ROS aggregation,decreased FTH1,GPX4,xCT,SLC40A1,p62,and NRF2 contents,increased Keap1 content,and decreased mitochondrial membrane potential(P＜0.05).Conclusion BJJP regulates ferroptosis in Huh7 HCC cells by inhibiting the p62/Keap1/NRF2 pathway,demonstrating potentials as a therapeutic agent for HCC.

Objective To analyze the coordination strategies of residual solvent control in various pharmacopoeias with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guidelines for residual solvents(ICH Q3C),aiming to provide ideas and solutions for coordinating residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Methods Through literature research and review,compare the coordination process between residual solvent control in various pharmacopoeias and ICH Q3C,analyze the implementation strategies of mainstream pharmacopoeia residual solvent control and ICH Q3C coordination in foreign countries,and clarify the differences in residual solvent control between the Chinese Pharmacopoeia and foreign pharmacopoeias.Results It is necessary to coordinate the control of residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Conclusion It is recommended to steadily promote the overall coordination of residual solvent control in Chinese pharmacopoeia and ICH by drawing on the experience of coordination between foreign pharmacopoeias and ICH Q3C,based on the national conditions of China.

Objective Exploring the ideas for coordinating the implementation of residual solvent control and ICH Q3C in the Chinese Pharmacopoeia standards for pharmaceutical excipients.Methods The relevant situation of residual solvent control in the current pharmaceutical excipient standards in Chinese pharmacopoeia was analyzed,and the progress of the International Conference on Harmonistion of Human Drug Registration Technology's Guidelines for Residual Solvents(ICH Q3C)and the coordination of foreign pharmacopoeias were compared and were analyzed.Results Proposed a coordination and implementation strategy between the Chinese Pharmacopoeia pharmaceutical excipient standards and ICH Q3C based on the association review mechanism.Conclusions The proposed coordinated implementation plan helps to improve the international integration of Chinese pharmaceutical excipient standard system,enhance the scientific and effective control of residual solvents in pharmaceutical excipients by regulatory authorities and the pharmaceutical industry,and comprehensively promote the translation and implementation of ICH Q3C guiding principles in Chinese pharmaceutical excipient standards.

Objective To explore the application value of iterative model reconstruction(IMR)technique in low-dose lumbar CT scanning.Methods A total of 48 patients who underwent lumbar CT plain scan were selected and divided into regular-dose group(group A)and ultra-low dose group(group B).The group A underwent imaging with 120 kV tube voltage,automatic tube current modulation technology,and iDose 4 reconstruction.The group B was scanned with a tube voltage of 100 kV and a tube current of 80 mAs,and the images of B1 and B2 groups were reconstructed by iDose 4 and IMR,respectively.The standard deviation(SD)value(the SD value represents the noise of the measured tissue),signal-to-noise ratio(SNR),and contrast-to-noise ratio(CNR)of cancellous bone,intervertebral disc,dural sac,and psoas muscle were measured and calculated at the L3-L4 vertebral body level.Two diagnosticians rated the image quality.Sample t-test and ANOVA were used to compare the measurement results and subjective scores.Results The comparison of SD for intervertebral disc,dural sac,and psoas muscle showed group B2＜group A＜group B1,while the subjective score comparison indicated group A＞group B2＞group B1.The SNR for intervertebral disc and psoas muscle demonstrated group B2＞group A＞group B1.There was no significant difference in bone quality score between group A and group B1(P＞0.05),but there was a significantly different between the bone quality scores of group B2 and those obtained with iDose 4 reconstruction(group A and group B1)(P＜0.05).The effective dose(ED)of group B was reduced by approximately 70.28％compared with group A.Conclusion IMR can significantly reduce SD,improves SNR and CNR,resulting in high-quality images.Compared to iDose 4 technique,IMR has more advantages in soft tissue display,while iDose 4 technique is superior in observing fine bone structures.The combined application of iDose 4 and IMR technique ensures high-quality images for diagnosis,while significantly reducing the radiation dose to patients.

Objective To explore the application value of CT combined with peripheral blood eosinophils(EOS)for distinguishing eosinophilic asthma(EA)from eosinophilic bronchitis(EB).Methods The clinical characteristics,peripheral blood EOS detection and imaging features of 523 patients(328 cases of EA and 195 cases of EB)were retrospectively analyzed.Univariate analysis identi-fied statistically significant parameters,which were further utilized in binary logistic regression to construct an imaging model and a combined model incorporating clinical characteristics,peripheral blood EOS and imaging features.Receiver operating characteristic(ROC)curves were plotted to evaluate the performance of each model.Results Statistically significant differences were observed between the two groups in age,body mass index(BMI),peripheral blood EOS count,peripheral blood EOS percentage,and 11 ima-ging features,including bilateral lung,bronchial wall thickening and bronchial mucus plugs(P＜0.05).The area under the curve(AUC)of the imaging model and the combined model were 0.891 and 0.918,respectively.Conclusion The combined application of CT and peripheral blood EOS detection can improve the efficiency,simplicity,and accessibility of distinguishing EA from EB.

Objective To explore the application value of CT combined with peripheral blood eosinophils(EOS)for distinguishing eosinophilic asthma(EA)from eosinophilic bronchitis(EB).Methods The clinical characteristics,peripheral blood EOS detection and imaging features of 523 patients(328 cases of EA and 195 cases of EB)were retrospectively analyzed.Univariate analysis identi-fied statistically significant parameters,which were further utilized in binary logistic regression to construct an imaging model and a combined model incorporating clinical characteristics,peripheral blood EOS and imaging features.Receiver operating characteristic(ROC)curves were plotted to evaluate the performance of each model.Results Statistically significant differences were observed between the two groups in age,body mass index(BMI),peripheral blood EOS count,peripheral blood EOS percentage,and 11 ima-ging features,including bilateral lung,bronchial wall thickening and bronchial mucus plugs(P＜0.05).The area under the curve(AUC)of the imaging model and the combined model were 0.891 and 0.918,respectively.Conclusion The combined application of CT and peripheral blood EOS detection can improve the efficiency,simplicity,and accessibility of distinguishing EA from EB.

Objective To analyze the coordination strategies of residual solvent control in various pharmacopoeias with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guidelines for residual solvents(ICH Q3C),aiming to provide ideas and solutions for coordinating residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Methods Through literature research and review,compare the coordination process between residual solvent control in various pharmacopoeias and ICH Q3C,analyze the implementation strategies of mainstream pharmacopoeia residual solvent control and ICH Q3C coordination in foreign countries,and clarify the differences in residual solvent control between the Chinese Pharmacopoeia and foreign pharmacopoeias.Results It is necessary to coordinate the control of residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Conclusion It is recommended to steadily promote the overall coordination of residual solvent control in Chinese pharmacopoeia and ICH by drawing on the experience of coordination between foreign pharmacopoeias and ICH Q3C,based on the national conditions of China.

Objective Exploring the ideas for coordinating the implementation of residual solvent control and ICH Q3C in the Chinese Pharmacopoeia standards for pharmaceutical excipients.Methods The relevant situation of residual solvent control in the current pharmaceutical excipient standards in Chinese pharmacopoeia was analyzed,and the progress of the International Conference on Harmonistion of Human Drug Registration Technology's Guidelines for Residual Solvents(ICH Q3C)and the coordination of foreign pharmacopoeias were compared and were analyzed.Results Proposed a coordination and implementation strategy between the Chinese Pharmacopoeia pharmaceutical excipient standards and ICH Q3C based on the association review mechanism.Conclusions The proposed coordinated implementation plan helps to improve the international integration of Chinese pharmaceutical excipient standard system,enhance the scientific and effective control of residual solvents in pharmaceutical excipients by regulatory authorities and the pharmaceutical industry,and comprehensively promote the translation and implementation of ICH Q3C guiding principles in Chinese pharmaceutical excipient standards.

Objective To explore the application value of iterative model reconstruction(IMR)technique in low-dose lumbar CT scanning.Methods A total of 48 patients who underwent lumbar CT plain scan were selected and divided into regular-dose group(group A)and ultra-low dose group(group B).The group A underwent imaging with 120 kV tube voltage,automatic tube current modulation technology,and iDose 4 reconstruction.The group B was scanned with a tube voltage of 100 kV and a tube current of 80 mAs,and the images of B1 and B2 groups were reconstructed by iDose 4 and IMR,respectively.The standard deviation(SD)value(the SD value represents the noise of the measured tissue),signal-to-noise ratio(SNR),and contrast-to-noise ratio(CNR)of cancellous bone,intervertebral disc,dural sac,and psoas muscle were measured and calculated at the L3-L4 vertebral body level.Two diagnosticians rated the image quality.Sample t-test and ANOVA were used to compare the measurement results and subjective scores.Results The comparison of SD for intervertebral disc,dural sac,and psoas muscle showed group B2＜group A＜group B1,while the subjective score comparison indicated group A＞group B2＞group B1.The SNR for intervertebral disc and psoas muscle demonstrated group B2＞group A＞group B1.There was no significant difference in bone quality score between group A and group B1(P＞0.05),but there was a significantly different between the bone quality scores of group B2 and those obtained with iDose 4 reconstruction(group A and group B1)(P＜0.05).The effective dose(ED)of group B was reduced by approximately 70.28％compared with group A.Conclusion IMR can significantly reduce SD,improves SNR and CNR,resulting in high-quality images.Compared to iDose 4 technique,IMR has more advantages in soft tissue display,while iDose 4 technique is superior in observing fine bone structures.The combined application of iDose 4 and IMR technique ensures high-quality images for diagnosis,while significantly reducing the radiation dose to patients.