Based on the theory of ti （character， 体） and yong （function， 用） in mental illness， ZHAO Yonghou's clinical experience in staged differentiation and treatment of schizophrenia is summarized. According to the theory， the core disease location of schizophrenia is in the brain， which is closely related to the organs， qi， and blood. It is proposed to interpret the pathogenesis of schizophrenia from the perspective of “zang-fu organs-qi and blood-brain and spirit”， that is， dysfunction of the zang-fu organs， disharmony of qi and blood， and malnourishment of the brain ti lead to dysfunction of the spirit ti and yong. In clinical practice， treatment of schizophrenia can be divided into four stages， for which the method of treating ti and yong simultaneously is suggested. In the prodromal stage， Liuwei Dihuang Decoction combined with Sini San （六味地黄汤合四逆散） with modifications is used to nourish the kidney and boost marrow， soothe the liver and rectify the spleen. For acute exacerbation with binding of phlegm and heat syndrome， Zhaoshi Yikuang Decoction （赵氏抑狂汤） with modifications is used to clear heat and dispel phlegm， awaken the brain and calm the mind. For phlegm-heat damaging yin pattern， Mengshi Guntan Pill combined with Zengye Decoction （礞石滚痰丸合增液汤） with modifications is used to clear heat and dispel phlegm， enrich yin and calm the mind. For the chronic treatment stage， Yudian Decoction （愈癫汤） with modifications is used to disperse phlegm and dissolve stasis， move qi and awaken the mind. For the rehabilitation and regulation stage， Shenan Pill （神安丸） with modifications is used to boost qi and nourish yin， and tranquilize the mind.

Schizophrenia has various obstacles in cognition， thinking， emotion， behavior and other aspects； it belongs to the category of “madness” in traditional Chinese medicine （TCM）. Once schizophrenia occurs， multiple factors are often intertwined， and a single therapy is difficult to be effective. At present， TCM compounds and active ingredients have significant effects in the clinical treatment of schizophrenia， which is an important direction for the development of new drugs for schizophrenia. This article summarizes the molecular mechanism of TCM compounds and active ingredients in the treatment of schizophrenia. It is found that Wendan decoction and Yudian decoction can inhibit the apoptosis of hippocampal cells by activating BDNF/TrKB/CREB signaling pathway； quercetin and icariin can promote neural development and regeneration by activating NMDA/ERK signaling pathway； Wendan decoction and icariin can maintain neural cell homeostasis by activating PI3K/AKT signaling pathway； Bushen zhuangyang capsule can enhance learning and memory abilities by activating CaMKⅡ signaling pathway； formulas such as Huatan huoxue tongzhi formula can enhance intercellular information transmission by inhibiting PKC signaling pathway； α-humulene and others can restore nerve cell function by inhibiting NRG1/ErbB4 signaling pathway. TCM compounds and active ingredients can improve schizophrenia by intervening in the above-mentioned signaling pathways.

As one of the most difficult-to-cure neuropsychiatric disorders in clinical practice， schizophrenia is mainly manifested by behavioral abnormalities and multidimensional cognitive dysfunction， and the recurrence rate and disability rate of the disease are increasing year by year， which seriously affects patients' social functioning and quality of life， and even threatens the physical and mental health of the surrounding population. At present， the treatment of schizophrenia is mainly based on antipsychotic drugs combined with psychotherapeutic techniques， which have limited long-term therapeutic effects and a high relapse rate. Traditional Chinese medicine （TCM） boasts the advantages of multi-targets， multi-pathways， multi-links， and multi-levels， and plays a crucial role in the prevention and treatment of schizophrenia and its prognosis. Phosphatidylinositol 3-kinase （PI3K） is widely present in cells and is involved in the regulation of protein synthesis and apoptosis， and the different isoforms of protein kinase B （Akt） are of great significance in cell growth， oxidative stress， neuronal development and other processes. In recent years， a large number of studies have found that the PI3K/Akt signaling pathway is closely related to schizophrenia. Through regulating the PI3K/Akt signaling pathway， TCM monomers and TCM compounds mainly affect key signaling molecules such as mammalian target of rapamycin （mTOR）， glycogen synthase kinase （GSK）， glucose transporter （GLUT） for glucose uptake and transport， and nuclear factor E₂-associated factor 2 （Nrf2）， which organize the intracellular network of centers and regulate the formation and plasticity of neuronal synapse， and they play an important role in mitigating schizophrenia by regulating the processes of cell proliferation， migration and apoptosis of neurons， and has the advantages of multi-targets， all-encompassing and low toxicity. This article analyzes and explains the mechanism of TCM intervention in the PI3K/Akt signaling pathway against schizophrenia， in order to provide a theoretical basis and reference for the prevention and treatment of schizophrenia by TCM.

Objective:To investigate alterations in brain functional connectivity (FC) in schizophrenia (SZ) model rats treated with Yudian decoction by using functional magnetic resonance imaging (fMRI).Methods:At 17th day of gestation in healthy SPF grade SD rats, a single intraperitoneal injection of methylazoxymethanol (MAM) (25 mg/kg) was used to induce abnormalities in monoamine neurotransmitters in pregnant female rats, thereby to establish a model of neural development abnormalities in the offspring. Four weeks old male offspring were selected as SZ model rats.Thirty SZ model rats were divided into model group, experimental group, and positive control group according to the body mass matching method, with 10 rats in each group. Additionally, 10 male offspring born to healthy female rats were selected as the blank control group.At 6 weeks of age, the rats in experimental group and positive control group were administered with Yudian decoction (1.54 g/kg) and risperidone (0.24 mg/kg) by gavage, respectively. The rats in blank control group and positive control group were administered with distilled water (6.7 mL/kg) by gavage.All the above interventions were conducted once a day for 14 consecutive days.The fMRI data were acquired from all samples using a 3.0 T MRI scanner. The bilateral hippocampus, bilateral prefrontal cortex, and bilateral striatum were designated as region of interest (ROI). FC comparisons between each pair of ROIs and whole-brain FC were conducted using two-sample t-test. Results:(1) Compared to the control group, the model group demonstrated enhanced whole-brain FC at the left cerebellar granular cell level (SIGMA: x=-2, y=-107, z=48) (cluster size=43, P<0.05, FWE adjusted under cluster-level). The experimental group exhibited increased whole-brain FC at the left cerebellar molecular layer (SIGMA: x=-5, y=-152, z=36) compared to the model group (cluster size=48, P<0.05, FWE adjusted under cluster-level). (2) Using the bilateral hippocampus as ROI, the positive control group exhibited enhanced FC at the deep layer of the superior colliculus (SIGMA: x=13, y=-77, z=27) compared to the model group (cluster size=88, P<0.05, FWE adjusted under cluster-level). The blank control group displayed decreased FC at the right granular insular cortex (SIGMA: x=43, y=19, z=9) compared to the model group (cluster size=125, P<0.05, FWE adjusted under cluster-level). Utilizing the bilateral prefrontal cortex as ROI, the experimental group showed reduced FC at the left cerebellar molecular layer (SIGMA: x=-14, y=-128, z=48) compared to the blank control group (cluster size=68, P<0.05 FWE adjusted under cluster-level). Conclusion:Schizophrenia is associated with abnormal whole-brain functional connectivity, notably characterized by enhanced functional connectivity in the hippocampal region.Yudian decoction demonstrates the capability to inhibit activity in the prefrontal cortex.

Objective To investigate the value of CT radiomics combined with CT and preoperative pathological features for predicting postoperative early recurrence(ER)of local advanced esophageal squamous cell carcinoma(LAESCC).Methods Data of 334 patients with LAESCC were retrospectively analyzed.The patients were divided into training set(n=234)and verification set(n=100)at the ratio of 7:3 and were followed up to observe ER(recurrence within 12 months after surgery)or not.Univariate and multivariate logistic regression were used to analyze clinical,CT and preoperative pathological features of LAESCC in patients with or without ER in training set.The independent risk factors of ER were screened,and a CT-preoperative pathology model was constructed.Based on venous phase CT in training set,the radiomics features of lesions were extracted and screened to establish radiomics model,and finally a combined model was established based on radiomics model and the independent risk factors.Receiver operating characteristic(ROC)curves were drawn,and the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of each model.Results Among 334 cases,168 were found with but 166 without ER.In training set,117 cases were found with while the rest 117 without ER,while in verification set,51 were found with but 49 without ER.The length of lesions,cT stage and cN stage shown on CT and tumor differentiation degree displayed with preoperative pathology were all independent risk factors for ER of LAESCC(all P＜0.05).The AUC of CT-preoperative pathology model in training set and validation set was 0.759 and 0.783,respectively.Ten best radiomics features of LAESCC were selected,and AUC of the established radiomics model in training set and validation set was 0.770 and 0.730,respectively.The AUC of combined model in training and validation set was 0.838 and 0.826,respectively.The AUC of CT radiomics combined with CT and preoperative pathological features in training set was higher than that of CT-preoperative pathologymodel and radiomics model(both P＜0.01).Conclusion CT radiomics combined with CT and preoperative pathological features could effectively predict postoperative ER of LAESCC.

ObjectiveTo explore the possible mechanism of Yudian Decoction （愈癫汤） in the treatment of schizophrenia. MethodTwenty male offspring from 5 normal female 17-day-pregnant SD rats were selected as blank group. Fifteen female 17-day-pregnant SD rats were injected intraperitoneally with methyl azomethine acetate （MAM） 25 mg/kg， and the male offspring simulated the neurodevelopmental abnormality to establish a rat model of schizophrenia. Sixty successfully-modeled rats were randomly divided into 20 rats in the model group， 20 rats in the Yudian Decoction group and 20 risperidone group. After 3 days of adaptive cage feeding， the rats in the Yudian Decoction group were gavaged with 1.54 g/（kg·d） of Yudian Decoction， the risperidone group was gavaged with 0.24 mg/（kg·d） of risperidone capsule， while the blank group and the model group were gavaged with 6.7 ml/（kg·d） of distilled water， once a day， for 14 consecutive days. Sample was collected on the day after the last gavage. The expression of glutamate receptor （GluR） and γ-aminobutyric acid receptor subunit α1 （GABAARα1）-positive neurons in the hippocampus and prefrontal cortex were detected by immunofluorescence， and the positive rate was calculated； the expression of small clear proteins （PVs） in the hippocampal CA1 region and the medial prefrontal cortex was detected by immunohistochemistry； The expression of glutamic acid decarboxylase 65 （GAD65） and glutamic acid decarboxylase 67 （GAD67） proteins and mRNAs in the hippocampus and prefrontal cortex were detected by immunoblotting and reverse transcription PCR. ResultCompared with the blank group， the positive rate of GluR in hippocampal area and prefrontal cortex of rats in the model group increased， the positive rate of GABAARα1 in hippocampal area decreased， the PV optical density value in hippocampal CA1 area and medial prefrontal cortex decreased， and the expression of GAD65， GAD67 proteins and mRNA in hippocampal area and prefrontal cortex decreased （P＜0.05 or P＜0.01）. Compared with the model group， GluR positivity rate in hippocampus and prefrontal cortex of risperidone group and Yudian Decoction decreased， GABAARα1 positivity rate in hippocampus increased， PV optical density value in hippocampus CA1 area and medial prefrontal cortex increased， and GAD65， GAD67 proteins and mRNA expression in hippocampus and prefrontal cortex increased （P＜0.05 or P＜0.01）. Compared with the risperidone group， the positive rate of GluR in hippocampus and prefrontal cortex and GABAARα1 in hippocampus in the Yudian Decoction group was reduced， the PV optical density value of hippocampal CA1 area was increased， the protein and mRNA expression of GAD67 in hippocampus area was elevated， and the protein expression of GAD65 in prefrontal cortex was reduced （P＜0.05）. ConclusionYudian Decoction may improve the pathological process of schizophrenia by regulating key regulators of glutamate/γ-aminobutyric acid （Glu/GABA） metabolic balance in the hippocampus and prefrontal cortex and maintaining the balance between neuronal excitation and inhibition.

Objective:To investigate the predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on computed tomogralphy(CT) radiomics and its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 202 patients with esophageal squamous cell carcinoma (ESCC) who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to June 2021 were collected. There were 147 males and 55 females, aged (63±8) years. Based on random number table, 202 patients were assigned into training dataset and validation dataset at a ratio of 7:3, including 141 cases and 61 cases respectively. Patients underwent radical resection of ESCC and enhanced CT examination. Observation indicators: (1) influencing factor analysis of malignant anas-tomotic thickening; (2) construction and evaluation of predictive model; (3) performance comparison of 3 predictive models. The normality of continuous variables was tested by Kolmogorov-Smirnov method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whintney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability. The consistency between subjective CT features by two doctors and measured CT numeric variables was analyzed by Kappa test and intraclass correlation coefficient (ICC), with Kappa >0.6 and ICC >0.6 as good consistency. Univariate analysis was conducted by corresponding statistic methods. Multivariate analysis was conducted by Logistics stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and area under curve (AUC), Delong test, decision curve were used to evaluate the diagnostic efficiency and clinical applicability of model. Results:(1) Influencing factor analysis of malignant anastomotic thickening. Of the 202 ESCC patients, 97 cases had malignant anastomotic thickening and 105 cases had inflammatory anastomotic thickening. The consistency between subjective CT features by two doctors and measured CT numeric variables showed Kappa and ICC values >0.6. Results of multivariate analysis showed that the maximum thickness of anastomosis and CT enhancement pattern were independent influencing factors for malignant anastomotic thickening[ hazard ratio=1.46, 3.09, 95% confidence interval ( CI) as 1.26-1.71,1.18-8.12, P<0.05]. (2) Construction and evaluation of predictive model. ① Clinical predictive model. The maximum thickness of anasto-mosis and CT enhancement pattern were used to construct a clinical predictive model. ROC curve of the clinical predictive model showed an AUC, accuracy, sensitivity, specificity as 0.86 (95% CI as 0.80-0.92),0.77, 0.77, 0.80 for the training dataset, and 0.78 (95% CI as 0.65-0.89), 0.77, 0.77, 0.80 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=1.22, P>0.05). ② Radiomics predictive model. A total of 854 radiomics features were extracted and 2 radiomics features (wavelet-LL_first order_ Maximum and original_shape_VoxelVolume) were finally screened out to construct a radiomics predictive model. ROC curve of the radiomics predictive model showed an AUC, accuracy, sensitivity, specificity as 0.87 (95% CI as 0.81-0.93), 0.80, 0.75, 0.86 for the training dataset, and 0.73 (95% CI as 0.63-0.83), 0.80, 0.76, 0.94 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=-0.25, P>0.05). ③ Combined predictive model. Results of multivariate analysis and radiomics features were used to construct a combined predictive model. ROC curve of the combined predictive model showed an AUC, accuracy, sensitivity, specificity as 0.93 (95% CI as 0.89-0.97),0.84, 0.90, 0.84 for the training dataset, and 0.79 (95% CI as 0.70-0.88), 0.89, 0.86, 0.91 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=0.22, P>0.05). (3) Performance comparison of 3 predictive models. Results of Hosmer-Lemeshow goodness-of-fit test showed that the clinical predictive model, radiomics predictive model and combined predictive model had a good fitting degree ( χ2=4.88, 7.95, 4.85, P>0.05). Delong test showed a significant difference in AUC between the combined predictive model and clinical predictive model, also between the combined predictive model and radiomics predictive model ( Z=2.88, 2.51, P<0.05 ). There was no significant difference in AUC between the clinical predictive model and radiomics predictive model ( Z=-0.32, P>0.05). The calibration curve showed a good predictive performance in the combined predictive model. The decision curve showed a higher distinguishing performance for anastomotic thickening character in the combined predictive model than in the clinical predictive model or radiomics predictive model. Conclusions:The maximum thickness of anastomosis and CT enhancement pattern are independent influencing factors for malignant anastomotic thickening. Radiomics predictive model can distinguish the benign from malignant thickening of anastomosis. Combined predictive model has the best diagnostic efficacy.

Objective:To investigate the application value of spectral computed tomo-graphy (CT) multi-parameter imaging in predicting gastric cancer lymph node metastasis.Methods:The retrospective case-control study was conducted. The clinicopathological data of 86 patients with gastric cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to June 2017 were collected. There were 53 males and 33 females, aged from 22 to 87 years, with a median age of 53 years. All patients received abdominal plain scan and arterial and venous phase contrast spectral scan. Images of plain scan, 70 keV monochromatic and iodine-based images in arterial and venous phase were analyzed on post-processing working station. Observation indicators: (1) gastric cancer lymph node metastasis; (2) analysis of influencing factors for lymph node metastasis in gastric cancer; (3) introduction of special cases. Count data were described as absolute numbers. Univariate analysis was performed using the chi-square test or rank sum test. Multivariate analysis was conducted using the Logistic regression model.Results:(1) Gastric cancer lymph node metastasis: of the 86 patients, 64 cases had lymph nodes metastasis and 22 had no lymph nodes metastasis. (2) Analysis of influencing factors for lymph node metastasis in gastric cancer: results of univariate analysis showed that tumor growth pattern, tumor diameter, infiltration of peritumor fat, CT value in arterial phase, CT value in venous phase, iodine value in venous phase were related factors affecting lymph nodes metastasis in gastric cancer ( χ2=6.753, Z=-3.180, χ2=7.649, Z=-2.051, -2.971, -2.547, P<0.05). Results of multivariate analysis showed that infiltration of peritumor fat and the iodine value in venous phase were greater than 12(100 μg/cm 3) and not greater than 16(100 μg/cm 3), or greater than 16(100 μg/cm 3) were independent risk factors affecting lymph nodes metastasis in gastric cancer ( odds ratio=13.154, 3.761, 7.583, 95% confidence interval as 2.597-66.620, 1.893-8.572, 4.769-16.692, P<0.05). (3) Introduction of special cases: case 1 was male, aged 46 years. Results of preoperative spectral CT enhanced scan showed gastric antrum space occupying lesion combined with enlarged lymph nodes. During enhancement arterial phase, spectral CT 70 keV monochromatic images and corresponding iodine-based images of primary lesion layer in the transverse view showed gastric wall thickening with mild to moderate enhancement, clear fat space in serosa and enlarged lymph nodes in lesser curvature. The spectral CT 70 keV monochromatic images and corresponding iodine-based images below pylorus level in the transverse view showed subpyloric enlarged lymph nodes. During enhancement venous phase, the 70 keV monochromatic images and corresponding iodine-based images of primary lesion layer in the transverse view showed layered enhancement of gastric antrum lesions and mucosal enhancement, with a high iodine value. The patient was diagnosed as gastric antrum cancer with lymph node metastasis, no serosal or peritumoral fat invasion. Results of postoperative pathological examination showed moderately differentiated adenocarcinoma of gastric antrum with serosal invasion and lymph node metastasis. Case 2 was male, aged 53 years. Results of preoperative spectral CT enhanced scan showed gastric cancer of lesser curvature combined with enlarged lymph nodes. During enhancement arterial phase, 70 keV monochromatic images and corresponding iodine-based images of primary lesion layer in the transverse view showed gastric wall heterogeneous thickening of lesser curvature, with moderate enhancement, obscure peritumor fat space, unclear serosa, and multiple enlarged lymph nodes in lesser curvature. During enhancement venous phase, 70 keV monochromatic images in the transverse view showed unclear boundary between lesions and enlarged lymph nodes in lesser curvature, obscure peritumor fat. During enhancement arterial phase, 70 keV monochromatic images of celiac trunk layer in the transverse view showed parasplenic artery lymph nodes, with circular enhancement and no enhancement in central necrotic elements. The patient was diagnosed as gastric cancer of lesser curvature with lymph node metastasis, serosal and peritumor fat invasion. Results of postoperative pathological examination showed poorly differentiated adenocarcinoma of gastric antrum with serosal invasion and lymph node metastasis. Conclusion:The infiltration of peritumor fat and iodine value in venous phase are independent factors affecting gastric cancer lymph node metastasis.

Objective To investigate the image quality and radiation dose of spectral CT with automatic spectral imaging mode selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) at abdominal CT as compared with low-kVp CT with ASIR.Methods Two hundred patients underwent the plain and arterial-phase (AP) and portal venous-phase (PVP) contrast-enhanced abdominal CT scan were analyzed prospectively.The patients were randomly assigned to the control group (low-kVp CT scan) and study group (spectral CT scan),if BMI ≤ 23.9 kg/m2,patients were assigned into group A (80 kVp) or group B (spectral CT with ASIS);if 24.0 kg/m2 ≤ BMI＜28.9 kg/m2,patients were assigned into group C (100 kVp) or group D (spectral CT with ASIS)(n=50 each).Groups A and B,groups C and D were matched by gender,age,body mass index,cross sectional area and contrast agent dose respectively.Low-kVp images and monochromatic images (40 to 60 keV) were all reconstructed by using ASIR.Radiation dose and quantitative parameters (image noise in HU and contrast-to-noise ratio of the liver,aorta and portal vein) were compared by using t test while overall image quality was assessed by Mann-Whitney U test between the matched groups.Results Radiation dose in the group B was significantly higher than group A (increased by 10％,P＜0.05) but there was no significant differences between groups C and D (P＞0.05).Compared to the control group,image noises in the study group were higher at 40 keV and 50 keV (P＜0.05),but similar at 40 keV (P＞0.05).At the energy level of 40 keV,the study group showed higher CNRs,but lower overall image quality scores than the control group except for the similar image quality scores between groups A and B during AP (P＜0.05).At the energy level of 50 keV,the CNRs and overall image quality scores in the study group were higher than or similar to the control group.At the energy level of 60 keV,the study group showed lower or similar CNRs,but higher or similar overall image quality scores compared with the control group.Conclusions The radiation dose of spectral CT with ASIS technique was slightly higher than 80 kVp CT but similar to 100 kVp CT.By combining ASIR technique,monochromatic image at 50 keV can maintain or improve CNR and overall image quality as compared with low-kVp images.

Objective To investigate the CT spectral imaging features of benign and malignant ovarian tumors and to assess the value of spectral CT in differentiating between benign and malignant ovarian tumors.Methods This study was granted by the institutional review board with a waiver for informed consent.34 patients with ovarian tumor(11 benign tumors and 23 malignant tumors)underwent preoperative CT scanning that included arterial phase (AP)and venous phase (VP)with GSI mode.Measurements were performed on the GSI viewer.The iodine concentration (IC,100 ug/cm3)was saved,and the normalized iodine concentration (NIC)and the spectral curve(spectral Hounsfield unit curve)were recorded.The slope of the curve was calculated as the formula:(CT attenuation (40 keV)-CT attenuation(100 keV))/60.The CT value was measured at 70 keV in Mono image.CT values,the slope of the spectral curve,the iodine concentration and NIC were compared between the two groups by using independent sample t-test with software SPSS 2 1.0.Receiver operating characteristic (ROC)was used to determine the threshold of slope of the spectral curve,the iodine concentration and NIC for differentiating benign and malignant ovarian tumors in VP.Results The slope of the spectral curve,the iodine concentration and NIC of malignant ovarian tumors in VP were 1.72±0.77,14.50±6.44 (100 μg/cm3),and 0.33±0.12.The slope of the spectral curve,the iodine concentration and NIC of benign ovarian tumors in VP were 1.05±0.48,8.86±4.04 (100 μg/cm3),and 0.22±0.13.Significant differences were found between the slope of spectral curve,the iodine concentration and NIC of the malignant ovarian tumors and those of the benign ovarian tumors in VP (P=0.01).CT values in double phases revealed no difference between these two groups (P>0.05).Conclusion There is a significant difference between the solid component of benign ovarian tumors and that of malignant ovarian tumors in spectral CT.GSI scan mode can provide more information for the differential diagnosis of benign and malignant ovarian tumors.