Drug-induced liver injury (DILI) is caused by the direct toxicity of drugs and/or their metabolites or the body-specific heterogeneous response to drugs. Since 2019, the European Association for the Study of the Liver, the American College of Gastroenterology, and the Asia Pacific Association of Study of Liver have successively updated previously published guidelines on DILI. Based on the above 3 updated guidelines and in combination with Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury, the Guideline for Primary Care of Drug-Induced Liver Injury (2019), and the relevant literature at home and abroad in recent years, we review the progress on the diagnosis and treatment of DILI in this paper, aiming to help the diagnosis and treatment of DILI in clinic.

Drug-induced liver injury (DILI) is caused by the direct toxicity of drugs and/or their metabolites or the body-specific heterogeneous response to drugs. Since 2019, the European Association for the Study of the Liver, the American College of Gastroenterology, and the Asia Pacific Association of Study of Liver have successively updated previously published guidelines on DILI. Based on the above 3 updated guidelines and in combination with Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury, the Guideline for Primary Care of Drug-Induced Liver Injury (2019), and the relevant literature at home and abroad in recent years, we review the progress on the diagnosis and treatment of DILI in this paper, aiming to help the diagnosis and treatment of DILI in clinic.

Objective To detect the serum level of transglutaminase 2 (TG2)-specific IgE (slgE) in patients with atopic dermatitis (AD),and to analyze its correlation with the disease condition.Methods A total of 77 patients with AD were enrolled into this study,including 44 patients aged ≥ 12 years and 33 patients aged ＜ 12 years.Of the 77 patients,20 were diagnosed with intrinsic AD,which was characterized by the absence of sIgE and total serum IgE values ＜ 150 kU/L,and 49 with extrinsic AD characterized by positive (++) or even strongly positive slgE for more than 1 kind of exogenous allergens,or total serum lgE values ≥ 150 kU/L.[mmunocapture-biotinylated detector enzyme immunoassay was performed to detect the serum level of TG2-sIgE in 77 patients with AD,40 adult patients with psoriasis vulgaris (PV) and 30 healthy adult controls.Clinical data on the AD patients were recorded,including age,disease duration,SCORAD score,blood eosinophil count,levels of total IgE and TG2-sIgE.Results The serum levels of TG2-sIgE in AD patients aged ≥ 12 years,AD patients aged ＜ 12 years,PV patients and healthy controls were 1.02 ± 0.2,1.04 ± 0.044,0.93 ± 0.25 and 0.71 ± 0.13,respectively.Additionally,the serum level of TG2-sIgE significantly differed among AD patients aged ≥ 12 years,PV patients and healthy controls (x2 =37.407,P ＜ 0.001),and was significantly higher in both AD patients aged ≥ 12 years and PV patients than in the healthy controls (t =7.38,4.83,respectively,both P ＜ 0.001).Moreover,the intrinsic AD group showed significantly higher TG2-sIgE levels compared with the extrinsic AD group (1.16 ± 0.03 vs.1.02 ± 0.20,t =2.27,P =0.02).The TG2-sIgE level was uncorrelated with the patients' age,disease duration,SCORAD score,blood eosinophil count or serum total IgE levels in AD patients (r =0.03,0.14,-0.04,-0.08,0.06,respectively,all P ＞ 0.05).Conclusion The serum level of TG2-sIgE obviously increases in AD patients,so TG2 may be one kind of autoantigen in AD patients,but there is no significant correlation between the TG2-sIgE level and AD severity.

A 59-year-old male patient presented with recurrent erythema and wheals all over the body for 6 years,complicated by irregular fever (the highest body temperature ＜ 39 ℃)and arthralgia for 2 months.He experienced a weight loss of 5 kg during two years prior to the presentation.Physical examination showed anemic comlexion,and there was no palpable enlargement of superficial lymph nodes,liver and spleen.Generalized erythema and wheals occurred all over the body,involving about 50％ of the body surface area.Histopathological examination of skin lesions showed infiltration of multiple neutrophilic granulocytes around blood vessels in the superficial dermis,and no vasculopathy was observed.Laboratory examinations revealed increased white blood cell (WBC) counts(13.97 × 109/L),erythrocyte sedimentation rate (ESR,136 mm/1 h) and C-reactive protein (CRP) level (75 mg/L),decreased hemoglobin level (96 g/L),and high serum levels of IgE (1 596 kU/L),IgG(20.4 g/L)and IgM(6 310 mg/L).Serum immunoelectrophoresis demonstrated that the IgM was a κ-type monoclonal immunoglobulin.Bone marrow examination showed active bone marrow hyperplasia.DNA sequencing analysis of 10 pairs of exons of the NLRP3 gene revealed 3 synonymous mutations,including c.663:C ＞ T:p.T221,c.732:G ＞ A:p.A244A and c.786:A ＞ G:p.R262R.Finally,the patient was diagnosed with Schnitzler's syndrome.There was no improvement of symptoms after the treatment with multiple oral antihistamines at increased dose levels.Then,the treatment protocol was adjusted to oral ciclosporin at a dosage of 200 mg/d for consecutive 18 days,but the patient still showed no response.After the treatment with oral prednisone (30 mg/d) and Tripterygium wilfordii tablets (66 μg thrice a day) for 2 weeks,the skin rashes subsided gradually,and arthralgia was relieved.Moreover,the WBC count,ESR and CRP level were decreased to 9.01 × 109/L,50 mm/1 h and 6 mg/L respectively,while the hemoglobin level was increased to 109.7 g/L.After 1-year follow-up,the dosage of glucocorticoids was gradually decreased to 8 mg/d.In addition,his condition was controlled well with no skin lesions and fever,except for occasional arthralgia in the knees and hip.

Objective To evaluate the recognition and uptake of transglutaminase 3 (TG3) by dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) receptors on the membrane surface of DC-SIGN-transfected human embryonic kidney (HEK) 293T cells and monocytederived dendritic cells (MDDCs).Methods The eukaryotic expression vector pGCMV-enhanced green fluorescent protein (EGFP) containing DC-SIGN gene fragments was transfected into HEK293T cells to prepare DC-SIGN-EGFP-HEK293T cells by using liposome transfection method.CD14+ monocytes were isolated from peripheral blood samples by magnetic bead-based negative selection,and then were induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to prepare MDDCs.Laser confocal microscopy and flow cytometry were performed to evaluate the recognition and uptake of TG3 protein by DC-SIGN receptors on the surface of HEK293T cells and MDDCs.MDDCs treated without Alexa Fluor 647 dye-tagged TG3 served as blank control group,and those treated with Alexa Fluor 647 dye alone served as negative control group.Results After co-culture with TG3 for 3 hours,laser confocal microscopy and flow cytometry both showed that TG3 could be recognized by and uptaken through DC-SIGN receptors into HEK293T cells and MDDCs.Flow cytometry also revealed that the binding of TG3 to MDDCs could be partially blocked by DC-SIGN blocking antibodies.Neither the negative control group nor the blank control group showed the recognition and binding of TG3 to HEK293T cells and MDDCs.Conclusion TG3 can serve as a kind of autoantigen to be recognized and bound by DC-SIGN receptors,followed by uptake by dendritic cells.

Objective To compare the therapeutic efficacy of combined biliary stent and 125I seed intracavity irradiation with palliative surgery in the treatment of extrahepatic ductal cholangiocarcinoma.Methods A prospective analysis was conducted on 142 patients with cholangiocarcinoma who were treated in The First Affiliated Hospital of Bengbu Medical College from January 2012 to December 2015.There were 80 patients who underwent percutaneous biliary metal stenting combined with 125I particles implantation (the stenting-particle group) and 62 patients who were treated by palliative biliary drainage (the surgical group).The surgical group included R1 resection in 17 patients,R2 resection in 26 patients and biliary enteric drainage in 19 patients).The levels of jaundice,liver function,survival time,hospitalization time and hospitalization cost before and after therapy were analyzed.Results Jaundice was effectively alleviated in the two groups after a short period.The liver function in the 2 groups improved significantly at 1,3 and 6 months when compared with that before operation,(P ＜ 0.05).The average hospitalization time of the stenting-particle group and the surgery group were (16.5 ± 5.0) days and (25.5 ± 10.5) days,respectively,(P ＜ 0.01).The average hospitalization cost of the stenting-particle group and the surgery group were (39 622.0 ± 7 666.4) yuan and (59 562.0 ± 24 218.2) yuan,respectively,(P ＜ 0.05).The average survival time of the stenting-particle group and the surgery group were (12.2 ± 5.1) months and (12.69 ± 7.46) months,respectively,and the difference was not significantly different (P ＞ 0.05).Conclusions For patients with extrahepatic ductal cholangiocarcinoma who were not suitable for radical surgery,percutaneous biliary stenting combined with 125I seed brachytherapy effectively reduced jaundice,improved liver function,shortened average length of hospital stay and reduced average cost of hospitalization.When compared with palliative surgery,it was a minimally invasive,easy,safe and efficacious treatment,especially for elderly patients with poor physical conditions.

There are various kinds of antihypertensive agents with complex chemical structures. Common antihypertensive agents are divided into 5 classes, including diuretics, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin Ⅱ receptor blockers and β-blockers, and can cause various types of drug eruptions. This review summarizes clinical characteristics, possible pathogenesis, treatment and consequences of antihypertensive agent-induced drug eruptions, including angioedema, and lupus erythematosus-like, psoriasis-like, eczematoid, herpetiform or lichen planus-like drug eruptions, in hope to facilitate their early detection, diagnosis and treatment, and to provide information and ideas for clinical and basic researches into them.

Objective To analyze γ?secretase gene mutations in a pedigree with acne inversa. Methods Clinical data were collected from a pedigree with acne inversa, which contained 30 members spanning 4 generations. Of these members, 12 were affected by acne inversa, and 9 of the affected members were alive. Peripheral blood DNA was obtained from the proband, his seven relatives (including 4 affected and 3 unaffected members), and 100 unrelatedhealthy human controls. PCR was performed to amplify all the coding exons and their flanking sequences of the NCSTN, PSEN1, PSENEN, Aph1 genes followed by DNA sequencing. Results A heterozygous insertion mutation (c.229_230insCACC)of the PSENEN gene, which led to translational frameshifting and resulted in dysfunciton of the PSENEN protein, was detected in all the 5 patients, but not in unaffected members or healthy controls. Conclusion There is a novel heterozygous insertion mutation c.229_230insCACC in the PSENEN gene, which may be the molecular basis of acne inversa in this family.

Skin microbiome maintain homeostasis with the host, and affect skin barrier and immune function. The components of skin microbiome are diverse and specific, and are affected by multiple factors. The predominance of Staphylococcus aureus and decrease in diversity of skin microbiome are a characteristic of atopic dermatitis. The overgrowth of S. aureus can aggravate inflammatory reactions in AD. S. epidermidis, although another predominant bacterium in AD, exerts an immunoprotective role by regulating skin barrier?associated immunoreactions through the dendritic cells, interleukin (IL)?17A?producing Th17 cells/IL?17 pathway, and by suppressing the overgrowth of S. aureus. Malassezia can induce and aggravate inflammatory reactions in AD through colonization, sensitization, cross reactions, and other mechanisms. Studies on skin probiotics may provide new directions for the treatment of AD.

Objective To explore renal clear cell carcinoma ( CCRCC) expression and significance of CD146 mR-NA in tumor tissue of patients with. Methods ELISA method for quantitative detection was used for CD146 protein and real-time PCR technique for the detection of CCRCC in 102 ( CCRCC) expression in tumor tissue of patients with CD146 mRNA, and 51 cases of renal patients with non tumor tissues as control. Results Found metastasis in patients with CCRCC, the CD146 protein concentration was statistically significant compared with the control group (F=52.1, P<0.01),the average expression of CD146 mRNA value (0.043 8±0.002 4) was significantly high-er than that of in situ CCRCC patients (0.038 2±0.001 1, P= 0.018) and control group (0.034 4±0.001 0, P=0.001 ) . Conclusion Pathological grading and lymph node up regulation of CD146 mRNA expression in renal cell carcinoma and metastasis, is expected to become a new index, evaluation of malignant degree of CCRCC me-tastasis and prognosis, and provide a reliable basis for the intervention of clinical treatment.