Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

Objective To investigate the regulation of synaptic plasticity by cannabinoid receptor 1(CB1R)and its effects on autism spectrum disorder(ASD)-like behavior.Methods CB1R-knockout(KO)mice and valproic acid(VPA)-induced ASD model mice(VPA mice)were used as study subjects.Behavioral experiments were used to assess the effects of CB1R on ASD-like behavior in mice,neuronal structural integrity and dendritic density were detected by microtubule-associated protein 2(MAP2)staining experiments,and the expression of synapse-associated proteins was detected by Western blot,to assess the effects of CB1R on synaptic plasticity.Results Behavioral result showed that VPA mice demonstrated significant ASD-like behavior,while CB1R-/-mice spent a significantly smaller proportion of residence time in the central region of the open field(P＜0.0001),showed significant increases in the number of marbles buried and self-grooming time(P＜0.01),significantly less time spent socializing with unfamiliar mice 2 and exploring unfamiliar objects(P＜0.001),and significantly more time exploring old objects(P＜0.05).The relative dwelling time was significantly reduced in CB1R+/-mice(P＜0.001),and the number of marbles buried and self-grooming time were significantly increased(P＜0.05).Synaptic plasticity assays revealed significant synaptic plasticity impairment in VPA mice.Hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/-and CB1R+/-mice,and expression levels of synapsin-1 were significantly increased(P＜0.05).Conclusions CB1R KO leads to ASD-like behavior such as anxiety and repetitive stereotyped behavior,social and cognitive impairments,as well as neuronal damage,dendritic dysplasia and disrupted synaptic protein expression in mice,suggesting that CB1R is involved in regulating synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.

ObjectiveTo adapt the Stanford Expectations of Treatment Scale（SETS） into Chinese（C-SETS） and test the feasibility， validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome（IBS-D） with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine（TCM）. MethodsWe obtained authorisation from the developer of the SETS， and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment； the feasibility was assessed by the recall rate， completion rate and the duration of filling out the scale； the reliability was assessed by Cronbach's α； the structural validity was assessed by exploratory and confirmatory factor analysis， and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items， with the 1st， 3rd， and 5th rating items constituting the Positive Expectations subscale， and the 2nd， 4th， and 6th rating items constituting the Negative Expectations subscale， each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%（96/96）， the completion rate was 89.58%（86/96）； Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854， respectively； exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4， and that the six entries could be used by both factors to explain 77.092% of the total variance； validation factor analysis showed that the goodness-of-fit index， comparative fit index， root mean square of approximation error， canonical fit coefficient， and chi-square degrees of freedom ratio took the values of 0.943， 1.003， 0， 0.943， and 0.626， respectively； and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility， reliability， and validity， which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.

Purpose To investigate the clinical and patho-logical characteristics,molecular characteristics,treatments and prognosis of adenoid cystic carcinoma(AdCC)of the breast.Methods A retrospective analysis was conducted on the clini-cal pathology of 14 breast AdCC patients,and HE,immunohis-tochemistry,FISH testing,and follow-up were performed.Re-sults All cases were female,aged 43～70 years.10 cases of classic AdCC and 4 cases of solid-basal cell AdCC(SB-AdCC)were included.The tumor was composed of epithelial,myoepi-thelial and basal-like cells arranged in sieve,tubular and solid pattern with fibrous mucinous or glassy changes in the stroma.The tumor cells of SB-AdCC were moderately to severely atypical with frequent mitosis and necrosis,accompanied by ductal carci-noma in situ(DCIS).Expression of ER(1/14),PR(1/14),HER2(0/14),CK7(14/14),p63(12/14),CK5/6(14/14),CD117(13/14),MYB(9/14)was detected;Ki67 index was 13.2％and 46.1％in classic AdCC and SB-AdCC,respec-tively.The MYB rearrangement rates in classic AdCC and SB-AdCC were 55.6％(5/9)and 25％(1/4),respectively.All patients were underwent surgical resection and/or radiotherapy and chemotherapy.During the follow-up period(2-62 months),1 SB-AdCC patient died due to lung and liver metasta-sis,while the other 10 patients survived without tumors.Con-clusion SB-AdCC is more invasive than classical AdCC with lower frequency of MYB gene rearrangement,and immunohisto-chemical detection of MYB protein has potential value in assis-ting the diagnosis of SB-AdCC.

Objective To investigate the effect of resistance training on the rehabilitation of patients after hip replacement with the framework of the theory of planned behavior(TPB).Methods A total of 85 patients of hip fracture patients in Gansu Provincial Hospital of Traditional Chinese Medicine from July 2022 to April 2023 were selected as research objects.The patients were separated into intervention group(n=43)and control group(n=42)by random sampling.Both groups were treated with routine nursing,and the intervention group was given resistance training based on TPB.The intervention time was 3 months.The Harris hip score(HHS),36-item short form(SF-36)score and Barthel index(BI)scores of the two groups were compared before intervention,1 month and 3 months after intervention,as well as the functional exercise compliance score of the patients 3 months after intervention.Results After 1 month and 3 months of intervention,the HHS,SF-36 score and BI score of intervention group were better than those of control group,and after 3 months of intervention,the executive ability of functional exercise in intervention group was significantly higher than that of control group,and the mean difference was significant(P＜0.05).Conclusion Resistance training led by TPB can effectively improve the functional exercise compliance of patients after total hip arthroplasty,improve the muscle strength,balance ability and joint stability of patients,and then improve the daily activity ability and quality of life.

ObjectiveTo investigate the value of combined determination of Model for End-Stage Liver Disease （MELD） score， albumin-bilirubin （ALBI） score， and β2-microglobulin in the diagnosis of liver cirrhosis with acute kidney injury （AKI）. MethodsClinical data were collected from 258 patients with liver cirrhosis who attended The First Affiliated Hospital of Zhengzhou University from October 2019 to October 2022， and according to the presence or absence of AKI， they were divided into AKI group with 117 patients and non-AKI group with 141 patients. The changes in each index were compared between the two groups and between the patients with different stages of kidney injury. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the efficacy of each index in the diagnosis of liver cirrhosis with AKI. ResultsCompared with the non-AKI group， the AKI group had significantly higher age （t=2.307， P=0.022）， proportion of patients with hepatic encephalopathy （χ²=18.064， P<0.001） or with spontaneous peritonitis （χ²=16.397， P<0.001）， mortality rate （χ²=45.251， P<0.001）， levels of creatinine （Z=-8.737， P<0.001） and β2-microglobulin （Z=-8.829， P<0.001）， and scores of CTP （Z=-4.058， P<0.001）， ALBI （t=2.563， P=0.011）， and MELD （Z=-5.628， P<0.001）， as well as a significantly shorter length of hospital stay （Z=-3.391， P=0.001）. There were significant differences in creatinine， β2-microglobulin， MELD score， and ALBI score between the patients with stage 1， 2 or 3 AKI （P<0.05）， while there was no significant difference in CTP score between these three groups （P>0.05）. The combined determination of ALBI score， MELD score， and β2-microglobulin had an area under the ROC curve （AUC） of 0.837 （95% confidence interval ［CI］： 0.782 — 0.892）， with a sensitivity of 75.2% and a specificity of 90.8%； ALBI score combined with MELD score had an AUC of 0.700 （95%CI： 0.636 — 0.764）， ALBI score combined with β2 microglobulin had an AUC of 0.823 （95%CI： 0.765 — 0.881）， and MELD combined with and β2 microglobulin had an AUC of 0.835 （95%CI： 0.779 — 0.890）， suggesting that combined determination of ALBI score， MELD score， and β2-microglobulin had a better diagnostic efficacy than ALBI score， MELD score， or β2-microglobulin used alone or in pairs， as well as a better diagnostic efficacy than creatinine. ConclusionCombined determination of ALBI score， MELD score， and β2-microglobulin has a relatively high value in the diagnosis of liver cirrhosis with AKI.

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.

Multidrug resistance （MDR） has been a main culprit behind the failure of chemotherapy in patients with malignant tumors and a major obstacle to improving the life quality and prolonging the survival of patients. Hepatocellular carcinoma cells， the innate drug-resistant cells， are generally insensitive to radiotherapy and chemotherapy. Moreover， as the early symptoms of hepatocellular carcinoma are atypical， most patients are diagnosed at the advanced stage， with short survival period and high recurrence rate. Thus， the sensitivity to chemotherapy drugs is decreased. This explains how MDR becomes one of the important reasons for the failure of primary hepatocellular carcinoma （PHC） treatment. Therefore， it is an urgent task to search for safe and effective chemosensitizers with little adverse effect in the research on the drug resistance of hepatocellular carcinoma. As Chinese medicine has been widely applied in the treatment of tumors， the mechanisms of compound Chinese medicine prescriptions， Chinese medicine injections， and single Chinese medicinal in reversing chemotherapy resistance in liver cancer have attracted the interest of scholars. According to previous reports， the mechanisms can be summarized as increasing intracellular drug concentration， influencing changes in enzyme activity， inducing apoptosis， reversing abnormalities in cellular signaling pathways， and regulating the tumor microenvironment. Traditional Chinese medicine reduces the chemotherapy resistance of hepatocellular carcinoma cells through multiple targets and multiple pathways， thereby improving the chemotherapy sensitivity of the cancer cells and enhancing the toxicity of chemotherapeutic drugs to hepatocellular carcinoma cells. Therefore， exploring the mechanism of MDR of hepatocellular carcinoma from the perspective of traditional Chinese medicine is important for reversing the MDR and is of great reference value for clinical treatment of hepatocellular carcinoma. However， there are few experimental types and adverse effects available. Thus， the multi-mechanism and multi-target experiments and clinical research should be carried out in the future.

Objective:To study the glypican 3 (GPC3) fluorescent probe imagings in hepatocellular carcinoma (HCC) tissues and to determine its prognostic value in HCC patients.Methods:The data of 87 patients who were treated at the Affiliated Hospital of Southwest Medical University from January 2019 to August 2020 were retrospectively analyzed. There were 75 males and 12 females, with the age of (56.1±11.9) years. The expressions of GPC3 were measured by immunohistochemistry and by the fluorescent probe. The results obtained by these two tests were compared. Patients were followed up for recurrence after hepatectomy. Univariate and multivariate Cox regression analyses were used to analyze factors influencing recurrence-free survival.Results:Detection of the GPC3 expression by GPC3 fluorescence probe was consistent with the results obtained by immunohistochemical studies ( Kappa=0.84, P<0.001). The positive rates of GPC3 fluorescent probe was 79.3%(69/87), compared with 80.4%(70/87) by immunohistochemistry studies, with no significant difference between the two groups ( P>0.05). The patients were then divided into the low differentiation group ( n=30) and the middle high differentiation group ( n=57) by the degrees of tumor differentiation. The fluorescence intensity in the low differentiation group was 134.4(128.0, 144.7) a. u. which was significantly different from the middle high differentiation group of 84.8(0, 108.5)a.u. ( Z=-7.52, P<0.001). The median fluorescence intensity of 87 patients with HCC was 108.6 a. u.. Multivariate Cox regression analysis showed that patients with a GPC3 fluorescence intensity ≥108.6 a. u. ( HR=2.07, 95% CI: 1.21-3.53, P=0.008) had a significant increased risk of recurrence after hepatectomy. Conclusion:The expressions of GPC3 in HCC were consistent between the studies by using either a GPC3 specific fluorescent probe or immunohistochemistry studies. A GPC3 fluorescence intensity ≥108.6 a. u. was a risk factor of recurrence after hepatectomy in patients with HCC.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a catastrophic illness. Few studies investigated the prognostic value of vitamin D-binding protein (VDBP) for hepatitis B virus (HBV)-related ACLF (HBV-ACLF) resulted in conflicting results. Methods: Two prospective HBV-ACLF cohorts (n=287 and n=119) were enrolled to assess and validate the prognostic performance of VDBP. Results: VDBP levels in the non-survivors were significantly lower than in the survivors (P<0.001). Multivariate Cox regression demonstrated that VDBP was an independent prognostic factor for HBV-ACLF. The VDBP level at admission gradually decreased as the number of failed organs increased (P<0.001), and it was closely related to coagulation failure. The areas under the receiver operating characteristic curve (AUCs) of the Child-Pugh-VDBP and chronic liver failuresequential organ failure assessment (CLIF–SOFA)-VDBP scores were significantly higher than those of Child-Pugh (P<0.001) and CLIF-SOFA (P=0.0013). The AUCs of model for end-stage liver disease (MELD)-VDBP were significantly higher than those of MELD (P= 0.0384) only in the case of cirrhotic HBV-ACLF patients. Similar results were validated using an external multicenter HBV-ACLF cohort. By longitudinal observation, the VDBP levels gradually increased in survivors (P=0.026) and gradually decreased in non-survivors (P<0.001). Additionally, the VDBP levels were found to be significantly decreased in the deterioration group (P=0.012) and tended to be decreased in the fluctuation group (P=0.055). In contrast, they showed a significant increase in the improvement group (P=0.036). Conclusions The VDBP was a promising prognostic biomarker for HBV-ACLF. Sequential measurement of circulating VDBP shows value for the monitoring of ACLF progression.