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 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.

Objective:To evaluate the clinical efficacy and impact on quality of life of the biofeedback (BF) therapy combined with the Wenyang Yiqi Prescription and self-efficacy interventions in patients with functional defecation disorders (FDD).Methods:A prospective, randomized controlled trial design was employed. A total of 128 FDD patients were selected from the Pelvic Floor Center of the Department of Proctology, Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, between January 2021 and April 2023. These patients were randomly divided into two groups, with 64 cases in each group. Additionally, 41 historical control patients, who had received conventional BF training between June 2015 and January 2018 at the same center, were included for comparison. The historical control group received conventional BF therapy, the intervention group 1 combined BF therapy with self-efficacy interventions, and the intervention group 2 added the Wenyang Yiqi Prescription based on intervention group 1's treatment. All three groups underwent two treatment courses. Constipation symptom scores before and after treatment were performed; self-efficacy was assessed via the Self-Rated Abilities for Health Practices scale (SRAHP); health behaviors were evaluated using the Health-Promoting Lifestyle Profile (HPLP); anxiety and depression were evaluated through Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS); quality of life was measured through SF-36. Clinical efficacy was evaluated based on constipation symptom scores.Results:During the treatment period, seven patients dropped out due to personal reasons, leaving 61 patients in intervention group 1 and 60 patients in intervention group 2 for efficacy analysis.　The total effective rates were 80.32% (49/61) in intervention group 1, 83.33% (50/60) in intervention group 2, and 56.10% (23/41) in the historical control group. The total effective rates of both intervention groups were significantly higher than those in the historical control group ( χ2=7.06, 9.15; P=0.029, 0.010, respectively). After treatment, intervention group 2 showed significantly lower constipation-related straining scores [1 (1, 2) vs. 2 (1, 2), Z=-4.51] compared to intervention group 1 ( P<0.05). Additionally, intervention group 2 had lower scores for straining [1 (1, 2) vs. 2 (1, 2), Z=-3.15] and defecation time [1 (0, 1) vs. 1 (1, 2), Z=-3.13] compared to the historical control group ( P<0.05). Psychological comfort efficacy (19.13 ± 2.51 vs. 16.98 ± 1.86, t=5.36), health responsibility efficacy (23.63 ± 4.69 vs. 22.59 ± 3.05, t=2.06), and overall SRAHP scores (75.98 ± 4.44 vs. 72.33 ± 5.16, t=4.17) were higher in intervention group 2 compared to intervention group 1 ( P<0.05). The HPLP scores (79.33 ± 11.13 vs. 72.80 ± 9.20, t=3.10) of intervention group 2 were higher than those of the historical control group ( P<0.05). Emotional functioning scores (75.98 ± 18.45 vs. 68.92 ± 20.58 and 68.55 ± 18.21, F=20.91) in intervention group 2 were higher than in both intervention group 1 and the historical control group ( P<0.05). Conclusion:The combination of the Wenyang Yiqi Prescription with BF therapy and self-efficacy interventions effectively improves the clinical symptoms and quality of life in FDD patients.

Objective To modify the dosage form of Guoganglong Sugar-Coated Tablets,and to investigate the chemical equivalence and pharmacodynamic equivalence between the new and old dosage forms of Guoganglong Tablets.Methods The preparation technology was screened by single-factor exploration with the indexes of hardness and dispersion uniformity,the quality standard was established by thin layer chromatography identification,high performance liquid chromatography(HPLC)content determination and charactertistics chromatograms,the constituents absorbed into blood were analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-Q-TOF-MS),and the pharmacodynamics was evaluated by anti-inflammatory experiment and analgesic experiment in mice model with inflammatory pain.Results The molding process of Guoganglong Dispersible Tablets was determined.A thin layer chromatographic identification method was established.A method for detecting the content of Guoganglong Tablets and the charactertistic chromatograms was established by HPLC,and a total of 15 common peaks were identified,with the similarity of the new-old dosage forms being greater than 0.9.A total of 12 constituents absorbed into blood were identified.Guoganglong Tablets could alleviate swelling degree of toes in mice with inflammatory pain,reduce the levels of interleukin 6(IL-6)in serum,improve spleen index,and increase the thermal pain threshold and acetic acid twisting frequency in mice.Conclusion The prescription process of Guoganglong Dispersible Tablets is stable,the quality standard is feasible,the chemical composition and pharmacological actions between the new and old dosage forms are basically the same,and in terms of certain indexes,Dispersible Tablets of Guoganglongare superior to Sugar-Coated Tablets.

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 effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

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.