ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

ObjectiveTo establish a geographical origin identification model for Foeniculi Fructus from Haiyuan， providing a new technical reference for the protection of Haiyuan's geo-authentic medicinal materials and its designation as a national geographical indication agricultural product. MethodsSamples of Foeniculi Fructus were collected from eight producing areas， including Minqin （Gansu）， Bozhou （Anhui）， Qingdao （Shandong）， Dezhou （Shandong）， Urumqi （Xinjiang）， Nujiang （Yunnan）， Gutuo （Inner Mongolia）， and Haiyuan （Ningxia）. Gas chromatography-ion mobility spectrometry （GC-IMS） was used to detect the volatile organic compounds （VOCs） in samples from these geographic origins. VOCs were qualitatively analyzed through dual matching with the National Institute of Standards and Technology （NIST） mass spectral database and the IMS drift time database. Using the Reporter module and Gallery Plot visualization tools within the LAV analytical platform， VOC fingerprint profiles characterizing geographic origins were constructed. A non-targeted analytical strategy was adopted， and 97 VOCs detected via GC-IMS were subjected to principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） based on their differential distribution patterns to construct an origin identification model for Foeniculi Fructus from Haiyuan region. Key discriminative markers were screened using variable importance in projection （VIP） values greater than 1. ResultsA total of 97 VOCs were identified， including alcohols， aldehydes， ketones， esters， organic acids， terpenoids， ethers， alkenes， and benzenes. The PLS-DA model， based on VOCs data obtained by GC-IMS， effectively distinguished Foeniculi Fructus in Haiyuan region from those of other origins. During cross-validation， the model achieved a prediction parameter （Q²） of 0.976 and a goodness-of-fit parameter （R²） of 0.936， with no overfitting observed in permutation testing. Twelve key flavor markers with VIP > 1 were identified as characteristic indicators of Haiyuan origin. ConclusionA stable and highly predictive origin identification model for Foeniculi Fructus from Haiyuan was successfully established using GC-IMS technology， PLS-DA， and VIP-based marker screening. This model provides a novel technical strategy for accurately distinguishing Foeniculi Fructus in Haiyuan region from other regional varieties and offers new technical support for its protection as a geo-authentic medicinal material and a nationally designated geographical indication agricultural product in China.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective:To explore the correlation of the dose of capecitabine with the efficacy and cardiotoxicity in patient-derived tumor xenograft (PDX) model of mice with colorectal cancer.Methods:The fresh cancer tissues of 1 colorectal cancer patient were transplanted into the bilateral axillary subcutaneous of immunodeficient NOG mice to establish PDX model and passage stably. And then the morphology of tumor cells in primary generation and the second-generation tumor tissues was observed by using HE staining. The expression of tumor markers was detected by using immunohistochemistry method, and the model was evaluated. Mice were intragastrically infused with 200, 300 and 400 mg/kg capecitabine once a day, which were treated as low, middle and high dose groups respectively, 5 rats in each group; in the control group, 0.9% NaCl solution was perfused into the stomach; 14 d in total, use stop for 7 d, consecutively administered in this way. The body weight was measured every day and the tumor volume was measured every 3 days. After 100 days of observation, the mice were killed, and the tumor tissue was taken to measure the tumor weight and then the tumor volume, tumor volume inhibition rate and tumor inhibition rate were calculated. The morphology of tumor tissues was observed by using HE staining. The protein levels of anti-tumor effect indexes like rasP21, cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), cardiac troponin Ⅰ (cTn-Ⅰ) and brain natriuretic peptide (BNP) in serum of mice were detected by using enzyme linked immunosorbent assay (ELISA).Results:PDX model of mice with colorectal cancer was successfully constructed, and the histological characteristics of the primary tumor in the model were well preserved. During administration, 1 mouse died in the capecitabine high dose group; a slow down in tumor volume growth could be found with the increased dose of capecitabine. There was no statistically significant difference in body weight among 4 groups until all mice were killed ( P > 0.05). The tumor volume and tumor weight in the low, middle and high dose groups were lower than those in the control group (all P < 0.05), and the tumor volume and tumor weight showed an obvious decrease with the increase in dose. The tumor volume inhibition rates of low, middle and high dose groups were 42.61%, 67.61% and 77.27%, respectively, and the tumor inhibition rates were 35.53%, 67.77% and 75.09%, respectively. The serum anti-tumor effect indexes rasP21, COX2 and PGE2 in the middle and high dose groups were decreased compared with those in the control group (all P < 0.05), while cTn-Ⅰ and BNP levels were increased compared with those in the control group (all P < 0.05). Conclusions:The established PDX model of mice with colorectal cancer can better retain the histological characteristics of the original tumor. After treatment of middle and high dose of capecitabine, the tumor inhibition effect is obvious, but the risk of myocardial damage should be noticed.

Objective: To understand the relationship between lipid metabolism and heart rate deflection point (HRDP) in Tibetan children in the high altitude area of Ganzi, and to provide reference for effective obesity prevention and physical exercise intervention for Tibetan children. Methods: From September to October 2019, 284 Tibetan primary school students living in Ganzi area were randomly selected. HRDP and deflection point speed with different body mass index (BMI) by increasing load method, as well as serum lipid metabolism were assessed. The correlation between the HRDP and lipid metabolism level was analyzed. Results: There were statistically significant differences in serum leptin, adiponectin, total cholesterol, and triglyceride levels among the first and second grade Tibetan primary school students in the Ganzi high altitude area with different nutritional status ( F =22.16, 10.12, 11.24, 4.35, P <0.05). The heart rate values at the HRDP in the first and second grades, the third and fourth grades, and the fifth and sixth grades under different nutritional status were compared, and the differences were statistically significant ( F =3.35, 4.76, 4.68, P <0.05). Pearson correlation analysis showed that there were statistically significant correlations between HRDP and serum leptin in the obese, overweight, normal, and lean groups in the first and second grades of primary school ( r =0.66, 0.14, 0.45, 0.65 , P <0.05). Conclusion There is a close relationship between HRDP and lipid metabolism of Tibetan children in the high altitude area of Ganzi, and the heart rate at the deflection point can be used as an effective reference intensity for exercise intervention in plateau children.

Objective:To explore the effect of combining inspiratory muscle training with diaphragm resistance training on the respiratory, motor and balance functioning of stroke survivors.Methods:Eighty-eight stroke survivors were randomly divided into a respiratory muscle training group and a control group, each of 44. Both groups received routine rehabilitation, but the respiratory muscle training group also received daily inspiratory muscle and diaphragm resistance training, five days a week for 4 weeks. The respiratory muscle strength, motor function and balance of the two groups were evaluated using the inspiratory muscle strength index, the Fugl-Meyer assessment scale and the Berg balance scale before and after the treatment.Results:After the treatment, the average inspiratory muscle strength index of the respiratory muscle training group was 61.80%, its average Fugl-Meyer score was 75 and its average Berg balance score was 38. All were significantly better than before the treatment and better than the control group′s averages at the same time point. Spearman correlation analysis found significant correlation among the three measurements.Conclusions:Combining inspiratory muscle training with diaphragm resistance training can significantly improve the inspiratory muscle strength of stroke survivors, and promote the recovery of their motor and balance functions.

Objective:To investigate the inhibitory effect of brazilin on bladder cancer cells and its mechanism.Methods:Chemically synthesized brazilin was synthesized by chemical synthesis. Methyl thiazolyl tetrazolium (MTT) method was used to detect the inhibitory effect of synthetic brazilin on bladder cancer cells T24 and BIU87. Proteomic technique was used to detect the effect of brazilin on the level of protein in both cells. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot methods were used to verify the effects of brazilin on the expression of protein regulator of cytokinesis 1 (PRC1) of both cells at gene and protein level.Results:MTT method showed that brazilin significantly inhibited the proliferation of bladder cancer cells T24 and BIU87, and its half inhibitory concentration ( IC50) of T24 cell and BIU87 cell was 9.9 μg/ml and 5.1 μg/ml,respectively. Proteomic results showed that brazilin could regulate the protein expression of PRC1 in both cells, which was verified by qRT-PCR and Western blot. Conclusion:Brazilin suppresses bladder cancer cell growth possibly by downregulating PRC1.

Objective:To investigate the effect of postsynaptic density-95(PSD-95)on long-term learning and memory impairment in neonatal rats induced by sevoflurane anesthesia.Methods:A total of 54 SD rats aged 7 days of SPF grade were randomly divided into 3 groups: control group (exposed to air), model group (exposed to 2.1% sevoflurane, 4 h/d, consecutive 3 days) and PSD-95 inhibitor group (inhaled sevoflurane+ intraperitoneal injection NA-1, consecutive 5 days), with 18 rats in each group.Morris water maze test and new object recognition test were used to detect the ability of visuospatial learning and memory and recognition memory of rats in each group.RT-qPCR was used to detect the mRNA levels of kalirin, Rac1 and PSD-95 in rat hippocampus.The expressions of kalirin, Rac1, PSD-95 and apoptosis related proteins Caspase-3, Bcl-2 and Bax in rat hippocampus were detected by Western blot.The expression levels of kalirin and Rac1 in hippocampus were detected by immunohistochemistry.SPSS 23.0 software was used for statistical analysis.Repeated measurement ANOVA and one-way ANOVA was used for comparing among groups.Results:Repeated measurement ANOVA showed that in the water maze test, the interaction between time and group of platform seeking latency and swimming distance of the three groups were significant ( Ftime×group=36.539, 41.548, both P<0.01). Simple effect analysis showed that the platform latency and swimming distance in the model group from day 2 to 6 were longer than those in the control group (platform latency from day 2 to 6: t=14.039, 17.147, 13.155, 13.831, 27.247, all P<0.01; swimming distance from day 2 to 6: t=10.122, 20.987, 7.267, 10.011, 8.121, all P<0.01). Compared with the model group, from day 2 to 6, the platform latencies of PSD-95 inhibitor group were prolonged( t=7.948, 14.768, 11.582, 12.832, 24.346, all P<0.01) and the swimming distances were increased( t=8.235, 24.325, 11.234, 12.031, 7.036, all P<0.01). The new object recognition test found that the new object exploration time in the model group was significantly longer than that in the control group ((21.30±2.27)s, (19.21±1.42)s, t=1.843, P<0.01), and the new object exploration time in the PSD-95 inhibitor group was significantly longer than that in the model group ((26.83±2.13)s, t=4.844, P<0.01). The difference index of novel objects in the model group was significantly lower than that in the control group ((0.41±0.12), (0.59±0.10), t=3.416, P<0.01), and the difference index of novel objects in the PSD-95 inhibitor group was significantly lower than that in the model group ((0.37±0.08), t=0.696, P<0.05). The qRT-PCR results showed that the expressions of Rac1, kalirin and PSD-95 mRNA in the model group were significantly lower than those in the control group ( t=9.969, 3.954, 6.561, P<0.05), and the expressions of Rac1, kalirin and PSD-95 mRNA in the PSD-95 inhibitor group were significantly lower than those of the model group ( t=2.132, 2.251, 3.502, all P<0.05). Immunohistochemistry results showed that the kalirin in the hippocampus CA1 area of the model group was significantly lower than that in the control group((8.18±1.94) vs (15.47±3.35), t=11.47, P<0.01), and kalirin in the PSD-95 inhibitor group was significantly lower than that in the model group((4.98±1.53), t=10.28, P<0.01); Rac1 in the model group was significantly lower than that in the control group ((3.72±1.53), (8.17±2.91), t=6.76, P<0.01), and the Rac1 in the PSD-95 inhibitor group(2.73±0.37) was significantly lower than the model group ( t=4.72, P<0.05). Western blot results showed that Caspase-3((1.37±0.16) vs (0.54±0.01), t=5.71, P<0.01) and Bax((1.87±0.31) vs (1.23±0.25), t=12.01, P<0.01) protein levels in the model group were significantly higher than those in the control group.Caspase-3 and Bax protein levels in the PSD-95 inhibitor group were significantly higher than those in model group (Caspase-3: (1.79±0.17), t=9.87, P<0.01; Bax: (2.19±0.21), t=16.19, P<0.01). The Bcl-2 protein level in the model group was significantly lower than that of the control group ((1.22±0.21) vs (1.96±0.38), t=11.92, P<0.01). And the Bcl-2 protein level in the PSD-95 inhibitor group (1.01±0.19) was significantly lower than that in the model group ( t=10.73, P<0.01). Conclusion:Sevoflurane anesthesia can damage the long-term learning and memory function and reduce the expression of PSD95 protein in neonatal rats.Inhibiting the expression of PSD95 can aggravate this damage, which may be related to the synaptic plasticity and apoptosis of neurons involved in PSD95.