Objective This study was performed to explore the use of intramuscular low-dose Zoletil(1.5 mg/kg)combined with isoflurane inhalation for tracheal intubation in miniature pigs while preserving spontaneous respiration by determining the 50％and 95％minimum alveolar concentrations effective inhaled(MAC EI50 and MAC EI95).The goal was to establish a safe anesthetic method for tracheal intubation in miniature pigs in which intubation is difficult.Methods Forty-four Bama miniature pigs underwent general anesthesia.Following sedation with an intramuscular injection of sufentanil,anesthetic induction was performed using mask inhalation of isoflurane with monitoring of the heart rate,blood pressure,respiration,body temperature,oxygen saturation,end-tidal carbon dioxide concentration,and end-tidal isoflurane concentration.The initial end-tidal isoflurane concentration was set at 2.0％.The tracheal intubation conditions and outcomes were evaluated using Cooper's scoring system,and the dose-response relationship was calculated using Dixon's up-and-down method.Probit regression was employed to calculate the MAC EI50 and MAC EI95 along with their 95％confidence intervals(CI).Results In tracheal intubation using direct laryngoscopy with induction by low-dose sufentanil combined with isoflurane inhalation in miniature pigs,the MAC EI50 was 3.10％(95％CI,2.79％～3.56％)and the MAC EI95 was 3.77％(95％CI,3.41％～6.42％).With proper monitoring and airway management planning in place,alveolar isoflurane concentrations ranging from 3.10％to 3.75％were able to maintain stable vital signs in the miniature pigs.Conclusions The use of Zoletil combined with isoflurane inhalation for tracheal intubation in miniature pigs,aimed at preserving spontaneous breathing,is a preferable and safe anesthetic method for oral airway management in miniature pigs with significant potential for widespread application.

Purpose Hydrogen proton magnetic resonance imaging was used to study the brain metabolism of menstrual-related migraine(MRM)in different states,and to investigate its correlation with clinical features and estrogen and progesterone.Materials and Methods We recruited 36 patients with MRM diagnosed by neurology outpatient experts of the First Affiliated Hospital of Henan University of Science and Technology from April 2019 to August 2022,and also recruited 29 normal women with age-and education-matched.Proton magnetic resonance spectroscopy was used to assess neurochemical brain changes during interictal period(late follicular phase)and ictal period(perimenstrual phase)in them.The point resolved spectroscopic sequence was used to focus on the bilateral medial prefrontal cortex(mPFC)and bilateral thalamus.Sex hormone levels were collected on the same day of MRI acquisition.The ratios of NAA/Cr,GABA/Cr,Glx/Cr and Cho/Cr were observed.Metabolite changes and hormone levels were investigated among two groups.Furthermore,metabolite changes were investigated in a longitudinal design during the interictal period and ictal period.Results There were no significant differences in the levels of estrogen and progesterone both in the late follicular and perimenstrual periods.There were no significant differences in decline rate of them in perimenstrual periods between patients and normal people(P>0.05).During interictal period,the ratio of Cho/Cr in the region of left mPFC was lower significantly in the MRM group than that of control group(U=-2.957,P=0.003)and showed a significant negative correlation with attack frequency(r=-0.398,P=0.018).During ictal period,the women with MRM had significantly lower the ratio of GABA/Cr in the left mPFC and higher the ratio of Glx/Cr in the left thalamus compared to those of controls(U=-2.015,P=0.044;t=2.213,P=0.033).We found no significant correlations between these results and magraine characteristics(P>0.05).In addition,we found the ratio of GABA/Cr did not change(P>0.05),the ratio of Glx/Cr and Cho/Cr in right thalamus increased from interictal towards the ictal state for MRM patients(t=-2.181,P=0.038;Z=-2.414,P=0.016).Conclusion The present study suggests the existence of distinct cerebral metabolism states between MRM and control,and there are dynamic changes in cerebral metabolism with headache attacks.However,there is no significant difference in estrogen and progesterone from normal women,and its neural mechanism still needs to be further studied.

Objective:To investigate the bidirectional causal relationship between schizophrenia and suicide or intentional self-harm using a Mendelian randomization (MR) approach.Methods:Using pooled data from a large-scale genome-wide association study, genetic loci that were independent of each other and associated with schizophrenia and suicide or intentional self-harm in populations of European ancestry were selected as instrumental variables. The data for schizophrenia included 76 755 patients with schizophrenia and 243 649 controls. Data for suicide or intentional self-harm included 1 058 patients with suicide or intentional self-harm and 307 942 controls. The inverse variance weighting (IVW) and weighted median methods of MR analysis were used to explore the bidirectional causality of schizophrenia and suicide or intentional self-harm using the ratio of ratios ( OR) as an evaluation index. Heterogeneity between individual single nucleotide polymorphism (SNP) was assessed by Cochran′s Q test. Mendelian randomization polymorphism residuals and outliers (MR-PRESSO) were used to detect SNP outliers, and MR-Egger regression tests were performed to examine the horizontal pleiotropy of SNPs. A "leave-one-out" sensitivity analysis was performed to test whether the MR study was influenced by individual SNPs. Results:The IVW approach showed that schizophrenia increased the risk of suicide or intentional self-harm ( OR=1.297, 95% CI=1.154-1.457, P<0.001). In addition, the above relationship was confirmed in the weighted median ( OR=1.232, 95% CI=1.038-1.461, P=0.017). Conversely, suicide or intentional self-harm was not causally associated with schizophrenia ( OR=0.969, 95% CI=0.927—1.012, P=0.157), again confirmed by the weighted median method. The Cochran′s Q test, MR-PRESSO and MR-Egger regression tests did not show heterogeneity or horizontal pleiotropy between instrumental variables. The "leave-one-out" sensitivity analysis confirmed that no single SNP had a disproportionate effect on the overall outcome. Conclusion:Schizophrenia is significantly and causally associated with an increased risk of suicide or intentional self-harm.

ObjectiveTo reveal the effects of different microbial agents on quality of Lycii Fructus by comparing the differences in the contents of multiple types of chemical components in Lycii Fructus after the application of different microbial agents. MethodTaking Ningqi No. 7 as experimental material， four microbial agents， namely Peiyuan combined with Xinterui（TP group）， Trichoderma harzianum combined with Bacillus subtilis（BW group）， Genwuyou（MT group） and Junyiduo（JYD group）， were applied， and no microbial agents was used as the blank group（CK group）. Then the contents of total phenolics， total flavonoids， saccharides， amino acids， nucleosides and bases， betaine and other components in Lycii Fructus were determined by ultraviolet spectrophotometry（UV）， high performance liquid chromatography（HPLC） and ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS）， and the methods such as multiple comparisons， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to analyze the effect of different microbial agents on the quality of Lycii Fructus. ResultMicrobial agents had different effects on chemical components of Lycii Fructus. The content of total phenolics was the highest in the TP group， and it varied significantly from the CK group（P<0.05）. The total flavonoid content was the highest in the BW group， followed by the TP group. Both polysaccharide and alduronic acid contents were the highest in the JYD group. Betaine content in the TP and BW groups were significantly higher than that in the CK group（P<0.05）. For the determined 23 kinds of amino acids， most of them were the lowest in the JYD group， and the highest in the MT group， while the nucleoside bases were higher in the MT and BW groups. It indicated that Lycii Fructus from different treatment groups could be distinguished clearly based on the determined 45 chemical components. The result of PLS-DA showed that the major differential components in each group were polysaccharides， glucose， fructose， betaine， alduronic acid， asparagine， sucrose， threonine， total flavonoids， alanine and total phenolics. The results of PCA composite scores based on the main differential components showed that composite scores of chemical components in each group were BW group>TP group>MT group>CK group>JYD group. ConclusionThe application of microbial agents of BW， TP and MT can promote the quality improvement of Lycii Fructus， and the application of JYD can promote the accumulation of polysaccharides and alduronic acid to a certain extent， but the overall effect on the quality of Lycii Fructus is not clear. This study lays the foundation for the green and healthy development of Lycii Fructus industry.

Objective : To investigate the protective effect and mechanism of Hudi Enteric capsules in ionizing radiation injury to small intestinal crypt cells (IEC⁃6 cells) in rats. Methods : IEC⁃6 cells were irradiated with 6 mega electron volt X ⁃rays (2 , 4 , 6 , 8 and 10 Gy) , cell clone formation assay was used to detect cell proliferation , and the 6 Gy ionizing radiation was selected to establish a cellular radiation damage model according to the cell survival rate. The effect of each concentration ( 12. 5 , 25 , 50 , 100 and 200 μg/ml) of Hudi enteric extract on the viability of IEC⁃6 cells was examined by cell counting kit⁃8(CCK⁃8) method , and the effect on the viability of IEC⁃6 cells after irradiation at ( 10 , 20 , 40 and 80 μg/ml) concentrations was examined according to the results. After obtaining the optimal irradiation dose and extract concentration , the cells were divided into control group , model group and Hudi extract group (80 μg/ml) , the control group was pseudo⁃irradiated and the other two groups received 6 Gy of ionizing radiation , and the Hudi enteric extract group was pre⁃treated with drugs 2 h before irradiation. Apoptosis was detected by Annexin V ⁃PI double staining; cell senescence was detected by β ⁃galactosidase (β⁃Gal) staining; reactive oxygen species was detected by DCFH⁃DA fluorescent probe ; the corresponding protein expression of p16 , p21 , Catalase (CAT) and Superoxide dismutase ( SOD2) was detected by Western blot. Results : The proliferation of IEC⁃6 cells was inhibited by radiation doses ranging from 4 Gy to 10 Gy(P < 0. 001) ; (P < 0. 001) , and the apoptosis rate , β ⁃Gal positivity rate and DCFH⁃DA fluorescence intensity in the Hudi enteric extract group were lower than those in the model group (P < 0. 05) . The protein expressions of CAT and SOD2 in the Hudi extract group were higher than those in the model group ( P < 0. 05) , and the protein expressions of p16 and p21 were lower than those in the model group (P < 0. 05) . Conclusion The mechanism of action of Hudi enteric capsules that attenuate radiation damage in IEC⁃6 cells may be related to the inhibition of reactive oxygen species production , reduction of oxidative stress , and attenuation of cellular senescence and apoptosis.

Objective:To investigate the bidirectional causal relationship between schizophrenia and suicide or intentional self-harm using a Mendelian randomization (MR) approach.Methods:Using pooled data from a large-scale genome-wide association study, genetic loci that were independent of each other and associated with schizophrenia and suicide or intentional self-harm in populations of European ancestry were selected as instrumental variables. The data for schizophrenia included 76 755 patients with schizophrenia and 243 649 controls. Data for suicide or intentional self-harm included 1 058 patients with suicide or intentional self-harm and 307 942 controls. The inverse variance weighting (IVW) and weighted median methods of MR analysis were used to explore the bidirectional causality of schizophrenia and suicide or intentional self-harm using the ratio of ratios ( OR) as an evaluation index. Heterogeneity between individual single nucleotide polymorphism (SNP) was assessed by Cochran′s Q test. Mendelian randomization polymorphism residuals and outliers (MR-PRESSO) were used to detect SNP outliers, and MR-Egger regression tests were performed to examine the horizontal pleiotropy of SNPs. A "leave-one-out" sensitivity analysis was performed to test whether the MR study was influenced by individual SNPs. Results:The IVW approach showed that schizophrenia increased the risk of suicide or intentional self-harm ( OR=1.297, 95% CI=1.154-1.457, P<0.001). In addition, the above relationship was confirmed in the weighted median ( OR=1.232, 95% CI=1.038-1.461, P=0.017). Conversely, suicide or intentional self-harm was not causally associated with schizophrenia ( OR=0.969, 95% CI=0.927—1.012, P=0.157), again confirmed by the weighted median method. The Cochran′s Q test, MR-PRESSO and MR-Egger regression tests did not show heterogeneity or horizontal pleiotropy between instrumental variables. The "leave-one-out" sensitivity analysis confirmed that no single SNP had a disproportionate effect on the overall outcome. Conclusion:Schizophrenia is significantly and causally associated with an increased risk of suicide or intentional self-harm.

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

Objective:To explore the mechanism of motor imagery training (MIT) combined with conventional rehabilitation to promote the functional recovery of upper limbs in stroke survivors. To explore the brain network reorganization resulting when motor imagery training (MIT) is combined with conventional rehabilitation to promote the motor recovery of stroke survivors.Methods:Fourteen hemiplegic patients were recruited as the MIT group. They underwent 4 weeks of MIT (30 min/day, 5 days/week) along with conventional rehabilitation treatment. The upper limb section of the Fugl-Meyer assessment (FMA-UE) and the modified Barthel Index (MBI) were used to assess all of the patients, and resting-state fMRI was performed before and after the treatment. Twenty-eight age- and sex-matched healthy subjects also received one-time resting-state fMRI scanning. Granger causal analysis was performed in the MIT group to calculate the changes in effective connection between the ipsilesional primary motor cortex and the whole brain before and after the treatment, and the results were compared with the healthy control group.Results:After the treatment, the average FMA-UE and MBI of the MIT group had increased significantly. Before the intervention, the effective connection mode of the ipsilesional M1 area in the MIT group was significantly different from that of the healthy controls. The causal flow from the ipsilesional M1 area to the bilateral prefrontal cortex had increased abnormally and the causal flow from the contralesional primary motor cortex, the inferior parietal lobule and the cerebellum to the ipsilesional M1 area had decreased significantly. After the treatment, the effective connection pattern of the stroke survivors was nearly normal, and the causal influence from contralesional motor imagery-related brain areas (the superior parietal lobule, inferior parietal lobule, thalamus and the fusiform gyrus) to the ipsilesional M1 area was enhanced. Effective connection from the ipsilesional M1 area to the contralesional cerebellum before the intervention was positively correlated with the improvement in FMA-UE scores, and the effective connection from the contralesional middle frontal gyrus to the ipsilesional M1 area was correlated negatively.Conclusions:The neural mechanism of MIT's effectiveness when it is combined with conventional rehabilitation might be related to the reorganization of effective connections. That would include enhanced causal flow between motor imagery-related brain areas and the contralesional cerebellum and ipsilesional M1 area. Down-regulation of the effective connection from the contralesional middle frontal gyrus to the ipsilesional M1 area also occurs.

Objective: To examine the longitudinal relationship between the prosocial behaviors and depressive symptoms in rural adolescents using a cross-lagged model,and to provide a reference for improving mental health of adolescents. Methods: Participants were junior school 372 students in grade seven recruited from a rural school in Anhui province, who filled the Strengths and Difficulties Questionnaire (SDQ) and a short version of Center for Epidemiological Survey Depression Scale (CESD-10) three times (once a year for 2 years),and the cross lag model is established. Results: Depressive symptoms(r=0.39-0.45) and prosocial behavior(r=0.43-0.46) of rural adolescents are relatively stable in junior middle school(P<0.01)；The depression score of adolescents in grade 9 was higher than that in grade 7 and 8(P<0.05) and girls’ depression score was higher than boys’ (F=7.94,P<0.01).The relationships between prosocial behaviors(T1, T2, T3) and depressive symptoms(T1, T2, T3) were all negatively correlated in rural adolescents(r=-0.23~-0.13, P<0.05). Depressive symptoms in T1 and T2 could negatively predict prosocial behaviors in T2 and T3, respectively (β T1-T2=-0.10, β T2-T3=-0.11, P<0.05), while prosocial behaviors in T2 could negatively predicted depressive symptoms in T3 (β=-0.14, P<0.05). Conclusion During the three years of junior high school, the depressive symptoms of rural adolescents negatively predicted prosocial behavior, and from the second to the third year of junior high school, prosocial behavior negatively predicted depressive symptoms.Community health workers should pay more attention on depressive symptoms of rural adolescents, which could be prevented and improved through prosocial behavioral intervention, including helping and sharing.