ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective To explore the impact of the clinical internship model at the on-campus rehabilitation outpatient clinic on the clinical practice abilities and employment intentions of students in the physical therapy program.Methods A total of 60 students from the 2020 cohort of the Rehabilitation Physical Therapy program at Kunming Medical University were selected as research subjects.In the first semester of their sophomore year,they were randomly divided into two groups:the three-phase clinical internship group at the on-campus rehabilitation outpatient clinic(n=30)and the conventional clinical internship group(n=30).The three-phase clinical internship group completed their clinical internship in three phases according to the training objectives at the on-campus rehabilitation outpatient clinic,while the conventional clinical internship group completed their internship according to the requirements of the internship syllabus.At the end of all clinical internships,assessments were conducted using a comprehensive theoretical examination of core professional courses,the Assessment of Physiotherapy Practice(APP),and an employment intention survey to evaluate the outcomes of the internships for both groups.Results After completing all internship tasks,there was no statistically significant difference in the scores of the comprehensive theoretical examination of core professional courses between the two groups(P>0.05).Similarly,there was no statistically significant difference in the total scores of the physiotherapy clinical practice assessment between the two groups(P>0.05).However,in the detailed assessments,the three-phase internship group outperformed the conventional group in professional behavior,communication,and evaluation(P<0.05).There were no statistically significant differences between the two groups in analysis and planning,intervention,evidence-based practice,and risk management(P>0.05).In the employment intention survey,70%of students in the three-phase internship group expressed a willingness to work in rehabilitation outpatient clinics or clinics,while only 46.6%of the conventional group did so.The comparison of employment intentions between the two groups showed a statistically significant difference(P<0.05).Conclusion The three-phase apprenticeship model of the on-campus rehabilitation clinic not only improves students'clinical practice ability,but also increases their confidence in seeking employment in the rehabilitation clinic,thus broadening the employment pathway for physiotherapy students.

Objective To explore the application value of distortion product otoacoustic emission (DPOAE) and speech in noise(SIN) testing in occupational health surveillance of noise-exposed workers. Methods A total of 220 noise-exposed workers was selected as the study subjects using the convenient sampling method. The study subjects participated questionnaire survey, personal noise exposure assessment, acoustic immittance testing, pure tone audiometry (PTA), DPOAE and SIN testing. According to PTA results, workers were enrolled into a high-frequency hearing loss (HFHL) group and a non-HFHL group. Results The detection rate of HFHL among the study subjects was 41.4%, and the detection rate of speech-frequency hearing loss was 15.9%. Workers′ bilateral DPOAE response amplitudes and signal-to-noise ratios at frequencies of 2.0-8.0 kHz in the HFHL group were lower than those in the non-HFHL group (all P<0.05). The DPOAE amplitudes at frequencies of 1.0-8.0 kHz in both ears of the study subjects were negatively correlated with the PTA threshold (all P<0.01), and were negatively correlated with age (all P<0.01). The signal-to-noise ratio loss score was higher among worker in the HFHL group than in the non-HFHL group (P<0.01) and was positively correlated with PTA thresholds (P<0.05). Conclusion DPOAE and SIN testing can detect early cochlear outer hair cell impairment and reduction of noise-related speech recognition ability in noise-exposed workers and may serve as an effective supplementary tool to routine PTA in occupational hearing surveillance.

Under the"Four Specials"conditions(special environments,special tasks,special equipment,and special personnel),complex tightly-coupled human-machine systems exhibit distinct characteristics such as human-in-the-loop,frequent human-machine interactions,and significant mutual influence between humans and machines.These features lead to prominent and typical human related safety issues.Through aggregating knowledge from literature review,accident case studies,and engineering practice,this paper elaborates on the characteristics of complex tightly-coupled human-machine systems,clarifies the definition of human related safety(including its research subjects,topics,and methods),and provides a systematic analysis framework on the causes of human related safety from a whole life-cycle perspective of system development.Furthermore,theoretical hypotheses are proposed for human related safety,along with its fundamental scientific research questions and methods.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.

Objective To investigate the impact of mitophagy,mediated by the long non-coding RNA SNHG16(LncRNA SNHG16)on diabetes-associated cognitive impairment(DCI).Methods 29 male C57BL/J mice were randomly divided into normal control(NC)group,DCI group and DCI+mitochondrial autophagy inhibitor(DCI+Mdivi-1)group.Morris water maze and new object recognition test were used to detect the cognitive function of mice,qRT-CPR was used to detect the expression of LncRNA SNHG16 and mitochondrial autophagy marker mRNA.Western blot were used to detect the expression of related protein.The mouse hippocampal neurons HT22 were divided into control(Con)group,high glucose(HG)group,HG+SNHG16 silencing(HG+sh-SNHG16)group and HG+no-load control(HG+sh-NC)group.CCK8 method and lactate dehydrogenase(LDH)method were used to detect neuronal damage.JC-1 method was used to detect mitochondrial membrane potential.Results Compared with NC group,the expression of LncRNA SNHG16 and the expression of autophagy-related gene 5,PTEN-induced putative kinase 1(PINK1),Parkin and microtubule associated protein light chain 3(LC3)Ⅱ/Ⅰ increased(P<0.05),while the expression of mitochondrial autophagy-related proteins P62 and mitochondrial outer membrane transposase 20(TOMM20)decreased in T2DM group.Compared with DCI group,the cognitive dysfunction of mice improved,and the expression level of LncRNA SNHG16 decreased in the DCI+Mdivi-1 group(P<0.05).The expressions of LncRNA SNHG16,LC3 Ⅱ/Ⅰ,PINK1 and Parkin were higher in HG group than in Con group(P<0.05),while the cell survival rate and TOMM20 protein expression were lower in HG group than in Con group(P<0.05).Silence of LncRNA SNHG16 can restore the activity of HT22 cells and mitochondrial membrane potential,and reduce the level of mitochondrial autophagy under HG condition.Conclusions The expression level of LncRNA SNHG16 was up-regulated in the hippocampus brain region of mice with diabetic cognitive dysfunction,and mitophagy was overactivated.Silencing of LncRNA SNHG16 inhibits mitophagy in hippocampal neurons and alleviates HG induced hippocampal neuronal damage.