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.

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.

BACKGROUND:Pain mechanisms in patients with lumbar disc herniation are associated with inflammation,autophagy is closely related to intervertebral disc diseases and inflammatory response,and aberrant miR-206 expression can trigger skeletal diseases. OBJECTIVE:To investigate the mechanism of miR-206 on inflammation,analgesia and autophagy related proteins in nucleus pulposus in rats with lumbar disc herniation. METHODS:Sixty SPF male Sprague-Dawley rats were randomly divided into control group,model group,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group.Animal models of lumbar disc herniation were established except for the control group.Ten days after modeling,miR-206 mimics-NC group,miR-206 mimics group,miR-206 inhibitor-NC group and miR-206 inhibitor group were injected with miR-206 mimics-NC(20 μmol/L,10 μL),miR-206 mimics(20 μmol/L,10 μL),miR-206 inhibitor-NC(20 μmol/L,10 μL)and miR-206 inhibitor(20 μmol/L,10 μL),respectively.Administration was given once a day for 4 continuous days.The control group and model group were injected with the same dose of normal saline.The paw withdrawal mechanical threshold of bilateral hind feet was measured by Von Frey filaments,and the paw withdrawal thermal latency of bilateral hind feet was measured by heat pain tester.The morphology of dorsal root ganglia was observed by hematoxylin-eosin staining.The expressions of inflammatory factors phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,and interleukin 1β in nucleus pulposus were detected by qPCR.The expressions of autophagy-related proteins LC3I and Beclin-1 were detected by western blot assay. RESULTS AND CONCLUSION:At 3,7,and 14 days after modeling,the paw withdrawal mechanical threshold and paw withdrawal thermal latency were both decreased in the model group compared with the control group,while the levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I and Beclin-1 increased(P<0.05).The above indexes showed no significant changes in the miR-206 inhibitor-NC group and miR-206 mimics-NC group compared with the model group(P>0.05).Compared with the miR-206 mimics-NC group,the miR-206 mimics group had lower paw withdrawal mechanical threshold and paw withdrawal thermal latency and higher levels of phospholipase A2,cyclooxygenase 2,prostaglandin E2,tumor necrosis factor α,interleukin 1β,LC3I,and Beclin-1 levels(P<0.05).Compared with the miR-206 inhibitor-NC group,the rats in the miR-206 inhibitor group showed opposite changes in the above indicators,and there were significant differences between the two groups(P<0.05).To conclude,inhibition of miR-206 can significantly improve the level of inflammatory factors in nucleus pulposus of rats with lumbar disc herniation,increase pain threshold,and reduce autophagy.The mechanism is related to the inhibition of LC3I and Beclin-1 expression.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.

Objective:To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) on the cellular tight junction protein Claudin-18 in endotoxin-induced acute lung injury (ALI).Methods:Eighteen healthy male C57BL/6 mice were divided into control group, endotoxin-induced ALI model group (ALI group) and Nrf2 activator tert-butylhydroquinone (tBHQ) pretreatment group (tBHQ+ALI group) according to random number table method, with 6 mice in each group. Mice endotoxin-induced ALI model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 15 mg/kg), and the mice in the control group was injected with an equal amount of phosphate buffer solution (PBS). The mice in the tBHQ+ALI group received three intraperitoneal injections of tBHQ (a total of 50 mg/kg) at an interval of 1 hour before molding. The last injection of tBHQ was accompanied by LPS of 15 mg/kg. The mice in the control group and model group were given equal amounts of PBS, and PBS or LPS was given at the last injection. The mice were sacrificed at 12 hours after LPS injection to take lung tissues. After the lung tissue was stained with hematoxylin-eosin (HE) staining, the pathological changes were observed under light microscopy, and the lung injury score was calculated. The lung wet/dry ratio (W/D) was determined. Nrf2 protein expression in the lung tissue was detected by Western blotting. Positive expression of Claudin-18 in the lung tissue was determined by immunohistochemistry.Results:The lung tissue showed normal structure, without significant pathological change in the control group. Compared with the control group, the alveolar septum widened accompanied by inflammatory cell infiltration, capillary hyperemia and tissue edema in the ALI group, the lung injury score and lung W/D ratio were significantly increased (lung injury score: 6.50±1.05 vs. 1.83±0.75, lung W/D ratio: 3.79±0.22 vs. 3.20±0.14, both P < 0.01), and the Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly lowered [Nrf2 protein (Nrf2/β-actin): 0.41±0.33 vs. 1.22±0.33, Claudin-18 ( A value): 0.28±0.07 vs. 0.44±0.10, both P < 0.05]. After tBHQ pretreatment, the degree of lung histopathological injury was significantly reduced compared with the ALI group, the alveolar space slightly abnormal, inflammatory cell infiltration and tissue edema reduced, the lung injury score and lung W/D ratio were significantly decreased (lung injury score: 3.00±0.89 vs. 6.50±1.05, lung W/D ratio: 3.28±0.19 vs. 3.79±0.22, both P < 0.01), and Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly increased [Nrf2 protein (Nrf2/β-actin): 1.26±0.09 vs. 0.41±0.33, Claudin-18 ( A valure): 0.45±0.04 vs. 0.28±0.07, both P < 0.05]. Conclusion:Nrf2 alleviated pulmonary edema and improved endotoxin-induced ALI by up-regulating Claudin-18 expression.

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 explore the value of multi-parameter spectral CT for differentiating grade G2-3 pancreatic neuroendocrine tumor(pNET)and pancreatic neuroendocrine carcinoma(pNEC).Methods Preoperative double-layer detector spectral CT(DLCT)data of 35 patients with pNET(pNET group,including 25 cases of G2 grade and 10 cases of G3 grade)and 17 patients with pNEC(pNEC group)were retrospectively analyzed.Conventional CT and spectral CT parameters were compared between groups,and those being significant different between groups according to univariate analysis were respectively incorporated into multivariate logistic regression to select the independent predictors for identifying grade G2-3 pNET and pNEC.Conventional CT model and spectral CT model were constructed,and the combined model was constructed based on the two.The efficacy of each model for distinguishing grade G2-3 pNET and pNEC was evaluated.Results CT values of lesions during venous phase(OR=0.939,P=0.025)and vascular invasion(OR=5.049,P=0.027)shown on conventional CT were both independent predictors,and conventional CT model was constructed,its area under the curve(AUC)for distinguishing grade G2-3 pNET and pNEC was 0.808.Normalized iodine concentration during venous phase(OR=0.603)and normalized effective atomic number during venous phase(OR=0.847)on spectral CT were both independent predictors(both P＜0.05),and spectral CT model was constructed.The AUC of spectral CT model was 0.894,higher than that of conventional CT model(Z=2.127,P=0.033).The AUC of combined model was 0.924,higher than that of conventional CT model(Z=2.302,P=0.021)but not significantly different with that of spectral CT model(Z=0.827,P=0.408).Conclusion Multi-parameter spectral CT could effectively differentiate grade G2-G3 grade pNET and pNEC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.