OBJECTIVE To explore the significance of pharmaceutical care through the diagnosis and treatment of a patient with exogenous insulin autoimmune syndrome （EIAS）， combined with the analysis of literature reports. METHODS Clinical pharmacist participated in the diagnosis and treatment process of one case of EIAS. Based on the characteristics of the patient’s condition， the pharmacist provided medication suggestions and formulated pharmaceutical monitoring measures. At the same time， the pharmacist searched for relevant literature on insulin autoimmune syndrome （IAS） and EIAS， extracted data （gender， age， occurrence time， laboratory tests， clinical symptoms， intervention and outcome）， and conducted analysis. RESULTS Based on the patient’s medication information in the past 3 years， clinical pharmacist determined that the EIAS was likely caused by insulin aspartate 30. The clinician adopted the clinical pharmacist’s suggestion to discontinue insulin and switch to oral hypoglycemic drugs. The patient improved after treatment. The literature analysis showed that among the 257 patients with IAS reported， 212 cases were caused by drugs； among them， 23 cases were caused by lipoic acid， and 56 cases were caused by exogenous insulin. There were no significant differences in age， glycosylated hemoglobin， and body mass index between the two groups. The lowest blood glucose level in the lipoic acid group was significantly lower than that in the exogenous insulin group （P＜0.05）. The proportion of females and the proportion of fasting insulin ≥ 1 000 μU/mL were significantly higher in the lipoic acid group than in the exogenous insulin group （P＜0.05）. CONCLUSIONS Compared with EIAS， lipoic acid-induced IAS usually causes more severe hypoglycemia， and the fasting insulin level is usually higher than 1 000 μU/mL， which is more common in female patients. The participation of clinical pharmacists in the diagnosis and treatment of EIAS can help improve the diagnosis and treatment level of similar rare diseases and ensure the safety of patients’ medication.

【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.

Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.

【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

Objective:To investigate epidemiological characteristics of Mycobacterium marinum infection cases in the Dermatology Hospital of Shandong First Medical University from January 2019 to December 2021. Methods:Data were collected from patients with Mycobacterium marinum infection in the Dermatology Hospital of Shandong First Medical University from January 2019 to December 2021. Demographic characteristics, clinical features and prognosis of patients were retrospectively analyzed. Differences between groups were analyzed using t test, Chi-square test and Fisher′s exact test; factors influencing the time to diagnosis (the time from the first appearance of skin manifestations to the diagnosis of Mycobacterium marinum infection in the hospital) longer than 12 months were analyzed using Chi-square test and multivariate logistic regression model, and the odds ratio ( OR) and 95% confidence interval (95% CI) were calculated. Results:From 2019 to 2021, a total of 373 cases of Mycobacterium marinum infection were diagnosed in the hospital, and the number of cases in 2021 was 4.06 times that in 2019; the male-to-female ratio was 1∶1.49, and their age was 54.24 ± 14.04 years. Among the 373 patients, 211 (56.57%) had a history of trauma caused by aquatic products (e.g., fishes, shrimps), of which 51 (24.17%) were stung by sea perch. Skin lesions involved unilateral limbs in 327 (87.67%) patients, only involved the hands or wrists in 188 (50.40%) patients, and 258 (69.17%) had multiple skin lesions. Among the 341 patients with treatment information, 105 (30.79%) were given one antibiotic, 214 (62.76%) received combination treatment with two antibiotics, and 15 (4.40%) were treated with three antibiotics. The response rate was 98.77% (321/325), and the time to diagnosis [ M ( Q1, Q3) ] was 5.03 (3.00, 8.37) months. Multivariate logistic regression analysis indicated higher proportions of males ( OR [95% CI]: 1.95[1.11 - 3.41], P = 0.02), patients aged > 55 years ( OR [95% CI]: 1.82[1.04 - 3.18], P = 0.04), patients with skin lesions only involving hands, arms or lower limbs ( OR [95% CI]: 3.48[1.83 - 6.61], P<0.001) among the patients whose time to diagnosis was longer than 12 months. Conclusions:The number of patients with Mycobacterium marinum infection was increased in the Dermatology Hospital of Shandong First Medical University year by year from 2019 to 2021, and fish sting wounds were the main cause of infection. The most common treatment regimen was the combination of two antibiotics, with a high efficacy profile.

Inflammatory bowel disease (IBD) is a group of chronic non-specific intestinal inflammatory diseases with unknown etiology. Irritable bowel syndrome (IBS)-like symptoms may occur in IBD in remission, which has a negative impact on the quality of life and prognosis of the disease. This article reviewed the progress of research on epidemiology, pathological mechanism, diagnosis and treatment of IBD in remission overlapping IBS-like symptoms both at home and abroad, in order to provide references for the diagnosis and treatment of IBD in remission and the management of chronic disease.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

OBJECTIVE：To study the prot ective effects of crocin （CR）against triptolide （TP）-induced visceral organ injury in mice，and to provide reference for the studying TP compatibility and detoxification. METHODS ：Fifty mice were randomly divided into normal group ，TP low-dose and high-dose groups （i.e. TP-L group ，TP-H group ，with 300，600 μg/kg），TP low-dose and high dose combined with CR groups （i.e. TP-L+CR group ，TP-H+CR group ，with 300 μg/kg TP+100 mg/kg CR ，600 μg/kg TP+ 100 mg/kg CR ），with 10 mice in each group. Except for normal group ，other groups were given relevant medicine intragastrically ， once a day ，for consecutive 7 d. The body weight of mice was weighted every day ，and their death was recorded. After last administration，the mice were sacrificed ，and the heart ，liver，kidney and testis were taken ，and the organ index was calculated ； serum levels of ALT ，AST，BUN and Scr ，the activity of T-SOD and the contents of MDA were all determined. The pathological changes of heart ，liver，kidney and testis were observed ；mRNA expression of Bcl- 2，Bax and caspase- 3 in liver tissue were determined. RESULTS ：Three，five，two and three mice in TP-L group ，TP-H group ，TP-L+CR group and TP-H+CR group died respectively，and the survival rates were 70％，50％，80％ and 70％，respectively. Compared with normal group ，the body weight （7th day of experiment ），heart index ，liver index ，kidney index （except for TP-L group ），testicular index ，T-SOD activity and mRNA expression of Bcl- 2 in liver tissue ，serum levels of ALT （except for TP-L group ），AST（except for TP-L group ），BUN and Scr，MDA content and mRNA expression of Bax ，mRNA expression of caspase- 3 in liver tissue were increased significantly （P＜ 0.05 or P＜0.01）. There were obvious pathological changes in heart ，liver，kidney and testis tissue. Compared with the same dose of TP alone group ，the above indexes of TP combined with CR group were improved in varying degrees. Except for the renal index and serum ALT level of TP-L+CR group ，there was statistical significance for all indexes （P＜0.05 or P＜0.01）；the pathological injuries of heart ，liver，kidney and testis were significantly improved. CONCLUSIONS ：CR can relieve the damage of heart ， liver，kidney and testis induced by TP ，which may be related to the antioxidant stress of CR.

Objective:To evaluate the relationship between the mitochondrial mechanism of diabetic mellitus-caused abolition of cardioprotection induced by ischemia postconditioning (IPO) and succinate dehydrogenase (SDH) in rats.Methods:Thirty-six SPF male non-diabetic Sprague-Dawley rats, aged 16-20 weeks, weighing about 300 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (ND+ Sham group), ischemia-reperfusion (I/R) group (ND+ I/R group) and IPO group (ND+ IPO group). Seventy-two rats with diabetes mellitus were divided into 6 groups ( n=12 each) using a random number table method: sham operation group (DM+ Sham group), I/R group (DM+ I/R group), DM+ IPO group, sham operation+ dimethyl malonate group (group DM+ Sham+ Dme), I/R+ dimethyl malonate group (group DM+ I/R + Dme) and IPO+ dimethyl malonate group (group DM+ IPO+ Dme). The model of cardiopulmonary bypass (CPB) was established, and the model of total I/R injury was induced by ligating the ascending aorta for 30 min followed by 60 min of reperfusion.The animals underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia starting from the onset of reperfusion in each IPO group.In each Dme group, dimethyl malonate was infused through the tail vein at a rate of 4 mg· kg -1·min -1 for 40 min starting from the beginning of CPB.At the end of reperfusion, the myocardial tissues were taken for measurement of mitochondrial respiratory control ratio (RCR) (by the Lufthansa electrode method), mitochondrial membrane potential (MMP) (by the JC-1 method) and the opening of mitochondrial permeability transition pore (mPTP) (by absorptiometry) and for determination of the activity of reactive oxygen species (ROS) (with the fluorescent probe), succinate dehydrogenase (SDH) (using spectrophotometric method) and the contents of succinic acid and fumarate. Results:Compared with ND+ Sham group, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly increased, and MMP, RCR and succinic acid content were decreased in ND+ I/R ( P<0.05). Compared with group ND+ I/R, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in ND+ IPO ( P<0.05). Compared with group DM+ Sham, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly increased, and MMP, RCR and succinic acid content were decreased in group DM+ I/R ( P<0.05). Compared with group DM+ I/R, no significant change was found in the parameters mentioned above in group DM+ IPO ( P>0.05). Compared with group DM+ IPO, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in group DM+ IPO+ Dme ( P<0.05). Compared with group DM+ I/R+ Dme, the activities of SDH and ROS, opening of mPTP and content of fumarate were significantly decreased, and MMP, RCR and succinic acid content were increased in group DM+ IPO+ Dme ( P<0.05). Conclusion:The mitochondrial mechanism of diabetic mellitus-caused abolition of cardioprotection induced by IPO may be related to the enhancement of SDH activity in rats.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth