ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 （GluR2）/Parkin signal-mediated mitophagy in rats with diabetes-related depression （DD）. MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin （STZ） tail intravenous injection + 28 days of chronic unpredictable mild stress （CUMS） combined with isolation. The rats were randomly divided into a normal group， a model group， a GluR2 blocker group （5 μg·kg^-1）， a GluR2 agonist group （10 μg·kg^-1）， a metformin + fluoxetine group （0.18 g·kg^-1 metformin + 1.8 mg·kg^-1 fluoxetine）， and high- and low-dose Zuogui Jiangtang Jieyu prescription groups （20.52 and 10.26 g·kg^-1， respectively）. The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling， respectively， while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate （ATP） in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine （5-HT） and dopamine （DA） in hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）. The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2， Parkin， regulating synaptic membrane exocytosis protein 3 （RIMS3）， and postsynaptic density protein 95 （PSD95） in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group， the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming （P<0.01）， lowered levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.01）， increased autophagosomes of hippocampal neurons， significantly damaged morphology and structure of dendrites and spines of hippocampal neurons， decreased expression levels of GluR2， RIMS3， and PSD95 in hippocampus， and an increased Parkin expression level （P<0.05， P<0.01）. Compared with the model group， the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes， respectively （P<0.05， P<0.01）. The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically， the two groups saw elevated levels of serum insulin and ATP， 5-HT， and DA in hippocampus （P<0.05， P<0.01）， restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons， up-regulated protein expression levels of GluR2， RIMS3， and PSD95， and down-regulated Parkin expression level （P<0.05， P<0.01）. ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats， the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.

Primary splenic lymphoma is a rare malignant neoplasm， with similar clinical manifestations to Sjogren’s syndrome and liver cirrhosis， which often leads to misdiagnosis. This article reports a case of primary splenic lymphoma misdiagnosed as Sjogren’s syndrome with liver cirrhosis， in order to improve the understanding of primary splenic lymphoma， Sjogren’s syndrome， and liver cirrhosis and avoid misdiagnosis and treatment delay.

【Objective】 To study and compare the effects of different storage temperature and time on coagulation factor after cryoprecipitated antihemophilic factor(CAF) melting, and to provide reference for the establishment of industry standards. 【Methods】 From June 2021 to May 2023, a total of 96 bags of CAF were sampled in 4 bags per month, and timely detected in the same month. After the CAF was melted in a 37℃ water bath, the mild to moderate lipemic blood was labeled. Each bag of CAF and two 50 mL transfer bags were divided into two bags and two groups of 20 mL each using a sterile adapter. One group was placed in a 4℃ refrigerator and the other in a 22℃ water bath for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h. Then 2 mL of aseptic sample was taken separately and put into the test tube, and 1mL of sample and 3 mL of buffer were added into the other test tube with the sampling gun and mixed on the machine for testing. The experimental data of 60 bags without mild to moderate lipemic blood cryoprecipitation and coagulation factor were randomly selected and statistically analyzed by SPSS21.0. 【Results】 After melting, CAF was stored for 0 h, 4 h, 8 h, 12 h, 24 h and 48 h to detect the average content and growth rate of coagulation factor in the two groups: 1) Storage at 4℃, factor Ⅷ content was 118.62, 111.57(-5.95%), 105.51(-11.05%), 103.30(-12.92%), 94.35(-20.46%) and 83.25(-29.82%) IU/ bag, respectively; Storage at 22℃, the factor Ⅷ content was 118.62, 112.69(-5.00%), 111.41(-6.08%), 109.01(-8.10%), 101.55(-14.39%) and 92.75(-21.81%) IU/ bag, and the storage results of the two groups were compared. At 24 h at 4℃ and 48 h at 22℃, the content of factor Ⅷ had significant statistical significance(P<0.01), and when stored at 22℃, the decay rate of factor Ⅷ was slower; 2) When stored at 4℃, the content of factor V was 41.19, 41.31(0.29%), 40.52(-1.64%), 40.27(-2.23%), 39.05(-5.19%) and 36.99(-10.21%) IU/ bag, respectively; Stored at 22℃, the factor V content was 41.19, 41.71(1.25%), 42.54(3.28%), 41.94(1.80%), 39.21(-4.80%) and 35.64(-13.48%) IU/ bag, respectively. Comparison of storage results between the two groups showed that the content of factor V was statistically significant(P<0.05) and significantly significant(P<0.01) at 4℃48 h and 22℃48 h, respectively, and the decay rate of factor V was faster when stored at 22℃; 3) When stored at 4℃, the Fbg content was 268.86, 268.17(-0.26%), 262.46(-2.38%), 270.50(0.61%), 267.52(-0.50%) and 261.92(-2.58%) mg/ bag, respectively; Stored at 22℃, the Fbg content was 268.86, 265.86(-1.12%), 264.12(-1.77%), 265.89(-1.11%), 266.04(-1.05%) and 261.04(-2.91%) mg/ bag, respectively. There was no statistical significance between the 2 groups and the original 0 h content in each time period(P>0.05). 【Conclusion】 After CAF melting, coagulation factor decreased with the extension of storage time, especially the decrease of factor Ⅷ, followed by factor V, while Fbg basically unchanged. Comparison between the two groups showed that, factor Ⅷ decay rate is slower, factor V decay rate is faster of storage at 22℃. CAF should be transfused as soon as possible after melting. If the delay is unavoidable, for the delay time less than 12 h, storage at 4℃ is recommended, fot the delay time more than 12 h and less than 24 h, storage at 22℃ is recommended.

Objective To assess the effect of ultrasonic thyroid artificial intelligence(AI)-assisted diagnostic system(AI-assisted diagnostic system)for diagnosing medullary thyroid carcinoma(MTC)compared with different physicians and taken papillary thyroid carcinoma(PTC)as the controls.Methods Totally 63 MTC,70 PTC and 62 benign thyroid nodules confirmed by pathology were enrolled.AI-assisted diagnostic system was utilized to analyze thyroid nodules and identify the likelihood of malignancy,and the probability value threshold was set at ≥0.40.All thyroid nodules were retrospectively reviewed and categorized by 3 physicians(1 senior physician,1 attending physician and 1 junior physician)according to Chinese thyroid imaging reporting and data system(C-TIRADS).The efficacy of AI-assisted diagnostic system and physicians for diagnosing MTC and PTC were evaluated.Results AI-assisted diagnostic system showed lower sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and area under the curve(AUC)for diagnosing MTC and PTC compared with physicians.Significant differences of AUC were found between senior physician and AI-assisted diagnostic system,as well as between attending physician and AI-assisted diagnostic system for diagnosing MTC and PTC(all P＜0.01),while no significant difference of AUC was between junior physicians and AI-assisted diagnostic system(both P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and AUC for AI-assisted diagnostic system for diagnosing MTC were all lower than those for diagnosing PTC,but the AUC was not significantly different(P＞0.05).Conclusion Ultrasonic thyroid AI-assisted diagnostic system had relatively high value for diagnosing MTC.

Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.

Objective Scutellaria baicalensis stems and leaves glucuronic hydrolase(sbsl GUS)was used to enzymatically hydrolyze scutellarin in Erigeron breviscapus(Vant.)Hand.Mazz.to prepare scutellarein,and the high-purity scutellarein was obtained through separation and purification.Methods Orthogonal experiments were used to optimize the process parameters for the extraction of Erigeron breviscapus(Vant.)Hand.Mazz..Using the rate of enzymatic hydrolysis conversion of scutellarin as the index,the amount of enzyme,pH,temperature,time and antioxidant were investigated,and the preparation process parameters of scutellarein were optimized.Ethanol extraction,activated carbon decolorization,and fractional crystallization were used to purify the crude extract.Results The extraction process was determined to be:segments of Erigeron breviscapus were decocted twice with 10 times water for 1 hour each time.The preparation process of scutellarein was as follows:the amount of sbsl GUS extract and Erigeron breviscapus decoction was 1∶10 based on crude drugs,0.5%sodium metabisulfite was added,pH value was about 6.0,the temperature was about 45℃,and the time was 20 hours.The crude extract of scutellarein with the content more than 60%was obtained.The crude extract was purified by fractional crystallization,refluxed with 80%ethanol,decolorized with activated carbon,concentrated and crystallized,and the scutellarein extract with content more than 85%was obtained.Conclusion sbsl GUS enzymatic hydrolysis technology,which was used to prepare scutellarein,is simple and feasible.This study provides a new way for the manufacture of scutellarein.

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula （左归降糖解郁方， ZJJF） for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group， model group， wingless MMTV integration site family member 5a （Wnt5a） agonist group， ZJJF group， and ZJJF plus Wnt5a inhibitor group， with 12 rats in each group. Except for the normal group， the rats were fed with high-fat chow， streptozotocin injection， and chronic mild unpredictable stress combination， to establish model of diabetes mellitus complicated with depression. After successful modelling， rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days； rats in ZJJF group were given 20.52 g/（kg·d） of ZJJF by gavage； rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage， and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5， with the same dosage and injection method as above. The normal group and model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention， the depression-like behaviour of rats was evaluated using the forced swimming experiment （immobility time） and the absent field experiment （number of activities）； the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated； the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining； the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside （Brdu） injection and immunofluorescence； RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a， Ras homologue genomic member A （RhoA） and Rho homologue-associated coiled-coil protein kinase 1 （ROCK1） in the dentate gyrus. ResultsCompared with the normal group， rats in the model group had significantly higher blood glucose， insulin and insulin resistance indices， longer immobility time， fewer activities， lower Brdu integral optical density values and Wnt5a， RhoA， ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus （P＜0.05 or P＜ 0.01）； the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken， and their length shortened. Compared with the model group， the blood glucose， insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced （P＜0.05 or P＜0.01）； the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened， the number of activities increased， the Brdu integral optical density values elevated， and the Wnt5a， RhoA， ROCK1 protein and mRNA expression elevated （P＜0.05 or P＜0.01）， and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased， the length lengthened， and the complexity of dendrites increased. Compared with the Wnt5a agonist group， rats in the ZJJF group showed significant decrease in blood glucose， insulin and insulin resistance indices， prolongation of immobilisation time， reduction in the number of activities， and reduction in the Brdu integral optical density value； except for the Wnt5a mRNA in ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. Compared with ZJJF group， Wnt5a， RhoA， ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group （P＜0.05 or P＜0.01）. ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression， and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.

ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis （GSEA） and short time-series expression miner （STEM）. MethodSD rats were randomly divided into six groups， including a normal group， a model group， high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription， and a positive drug group. The model of diabetes with depression was established by high-fat feeding， streptozotocin （STZ） injection， and chronic mild unpredictable stress. The high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52， 10.26， and 5.13 g·kg^-1 respectively. The positive drug group was orally administered 0.18 g·kg^-1 metformin and 1.8 g·kg^-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days， the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay （ELISA）. Three hippocampus samples were randomly selected from the normal group， the model group， the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis， GSEA analysis， and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR （Real-time PCR）. The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group， the fasting blood glucose， cholesterol， and triglyceride levels in the model group were significantly increased （P<0.01）. Moreover， the immobility time in the forced swimming test was significantly increased， while the time to climb the platform was significantly prolonged， and the search distance in the target quadrant was significantly reduced in the Morris water maze test （P<0.05，P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose， cholesterol， and triglycerides in rats with diabetes with depression （P<0.05，P<0.01）， reduced the immobility time in the forced swimming test， shortened the stage time in the Morris water maze test， and increased the search distance ratio in the target area （P<0.05，P<0.01）. Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group， while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription， with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group， and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription， with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group， model group， and high dose group of Zuogui Jiangtang Jieyu prescription， two significantly different trend clustering groups were obtained. One key gene set for axonal guidance， as well as key target signal elements Sema3c， Sema7a， Robo3， Epha8， and Epha7， were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group， the mRNA expression of Robo3， Sema7a， and Epha7 in the hippocampus of the model rats was significantly reduced （P<0.05， P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3， Sema7a， and Epha7 （P<0.05， P<0.01）. Western blot results showed that compared with the results in the normal group， the Sema7a， ITGB1， and FAK protein expression in the hippocampus of the model group was significantly reduced （P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a， ITGB1， and FAK in the hippocampus （P<0.05，P<0.01）. ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.

Objective:To investigate how to integrate the ideological and political elements into the teaching of Nutrition and Food Hygiene under the background of new medical science.Methods:Through literature review and teaching discussion,suitable ideological and political elements and cases were selected to be integrated into the teaching of Nutrition and Food Hygiene,and feasible strategies were initially explored,which were implemented and evaluated in the grade 2018 students majoring in preventive medicine in Bengbu Medical College.Results:About 94.65% (124/131)of the students were satisfied with the ideological and political content design of the course,97.71% (128/131)of the students thought that it would be helpful to expand their professional knowledge,93.13% (122/131)thought that it would be helpful to establish morality and cultivate talents,and the overall feedback was good.The ideological and political teaching was generally recognized.Conclusions:It is feasible to integrate ideological and political elements into professional core courses,and to a certain extent.It can enrich the content of professional courses,improve students'interest,and make"foster virtue through education"truly implemented in the cultivation of professional quality.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.