Background:Drug-induced liver injury( DILI)is a kind of commonly seen diseases,in which typical clinical manifestations are lacking and misdiagnosis and missed diagnosis are frequently occurred. Aims:To investigate the clinical characteristics of patients with DILI. Methods:Clinical data of patients with DILI at Zhongshan Hospital,Xiamen University from January 2014 to December 2015 were collected. Clinical characteristics were retrospectively analyzed and the relationship between clinical characteristics and prognosis was investigated. Results:A total of 51 patients with DILI were enrolled,the ratio of male to female was 1∶ 1. 32,the average age at diagnosis was(50. 6 ± 17. 9)years old,the highest proportion(43. 1% )of patients were aged 60 and older. Hepatocellular damage was the main type of liver injury (84. 3% ). Chinese herbs,cardiovascular drugs,hormone and endocrine drugs were the most common drugs causing DILI, which accounted for 51. 0% ,19. 6% and 9. 8% ,respectively. Concomitant diseases of DILI covered many systems. The clinical manifestation of DILI was atypical,and the laboratory examination also lacked specificity. The positivity rate of autoimmune antibody was 5. 9% . Most patients had good prognosis,and the cure rate and improvement rate were 21. 6%and 66. 7% ,respectively. The mortality rate was 5. 9% with the cause of death being liver failure. Levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin,prothrombin time(PT) and international normalized ratio( INR) at admission were correlated significantly with prognosis( P ﹤ 0. 05 ). Conclusions:DILI commonly occurs in elderly population,and inappropriate use of Chinese herbs maybe the important cause. The clinical manifestation of DILI is not typical,and most patients have good prognosis. Levels of ALT,AST, TBIL,albumin,PT and INR at admission are correlated significantly with prognosis.

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Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.

Objective To observe the clinical therapeutic effects and evaluate the security of Huganjiexian decoction combined with conventional therapy on hepatic cirrhosis.MethodsBy the randomized and prospective study method,34 patients with liver cirrhosis were divided into experimental group and control group.The experimental group was treated with Huganjiexian decoction combined with conventional therapy while the control group was treated with conventional therapy alone.Patients in both groups were treated six months.At the beginning and 6 months after treatment,levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),albumin/globulin (A/G),total bilirubin (TBiL),blood urea nitrogen (BUN),serum creatinine (Scr) were determined.Results Levels ofALT、AST、TBiL decreased in both groups after being treated for six months,and the differences of downward trend of the experimental group were more significant than control group (F=36.63,40.31,38.65,P＜0.05).Levels ofALT、AST、TBiL of the experimental group were lower than those of control group significantly (F=8.67,7.62,4.36,P＜0.05 ).The A/G raised in both groups after treatment,and the upward trend of the experimental group was greatly different from that of control group (F=24.10,P＜0.05),the value of A/G of the experimental group was higher than that of control group (F=4.78,P＜0.05).The ALB raised in both groups after treatment,while the upward trend of the experimental group was no different from that of control group (F=0.89,P＞ 0.05).Thevalue of ALB had no significant changes in both groups (F=3.15,P＞0.05).Conclusion Huganjiexian decoction possessed therapeutic effect on hepatic cirrhosis,it had no obvious toxicity and side

Objective:To evaluate the safety and efficacy of a novel domestic extracorporeal membrane oxygenation (ECMO) mainframe in a porcine model, and to provide the basis for further clinical application.Methods:Five domestic healthy male white pigs, weighing (51±4) kg, were selected. The ECMO system was established by using a novel ECMO mainframe with imported membrane oxygenator and pipeline, and continued to run for 72 hours. ECMO parameters are as follows: veno-arterial ECMO, centrifugal pump speed 3 000-3 500 r/min, continuous infusion of heparin anticoagulation to maintain the activate clotting time (ACT) of 140-200 s. Real-time monitoring of speed, flow, pressure before pump, pressure after pump, pressure after membrane and other equipment parameters, and the equipment performance was scored. The changes of hemodynamics, blood lactic acid and blood routine were monitored dynamically. Repeated measures analysis of variance was used to compare different time points within the group. At the end of the experiment, the thrombosis in the pump head and oxygenator was observed. The animals were sacrificed to obtain the tissue samples of the main organs for gross observation and pathological injury evaluation.Results:All animals successfully ran the ECMO system for 72 hours. (1) The centrifugal pump speed should be maintained at 3 029-3 483 r/min, the flow rate was maintained at 2.24-2.60 L/min, The pressure before the pump between minus 107.57 and minus 31.86 mmHg, the pressure after the pump was 197.50-282.43 mmHg, and the pressure after the membrane was 178.71-261.5 mmHg, all were in the normal range, and there was no significant difference between different time points (all P>0.05). The performance scores of the mainframe were all 4 points or above, indicating that the use requirements were met. (2) The heart rate of the animals was 50-80 beats /min, the mean arterial pressure was 85-115 mmHg, and the lactic acid was 0.996-2.25 mmol/L, all within the normal range, and there was no significant difference between different time points (all P>0.05). The free hemoglobin was 8.98-16.39 mg/L, and the hemoglobin was 6.58-7.52 g/L, both within a reasonable range, and there was no significant difference between different time points (all P>0.05). The platelet count was 69.6-231.6×10 9/L, and showed a continuous downward trend ( P<0.05). ACT was maintained at 135-169 s, which was within the target range, and there was no significant difference between different time points ( P<0.05). (3) At the end of the experiment, there was no obvious thrombosis in the pump head and oxygenator, no obvious thrombosis or infarction in the heart, brain, liver, lung and kidney, and no obvious hemorrhage or necrosis under the microscope. Conclusions:The ECMO established by the novel domestic ECMO mainframe combined with imported membrane oxygenator and pipeline ran smoothly for 72 hours, achieving the target of effect and safety.

ObjectiveTo summarize the liver biopsy and clinical features of patients with liver injury of unknown origin， and to investigate the value of ultrasound-guided percutaneous liver biopsy in the diagnosis of liver injury of unknown origin. MethodsA retrospective analysis was performed for the clinical data and ultrasound-guided percutaneous liver biopsy results of 94 patients with liver injury of unknown origin who were admitted to Zhongshan Hospital， Xiamen University， from January 2018 to February 2023. According to the proportion of the patients with different final diagnoses， the patients were divided into autoimmune liver disease （AILD） group， metabolic associated fatty liver disease （MAFLD） group， drug-induced liver injury （DILI） group， alcoholic liver disease （ALD） group， and unknown group. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Bonferroni analysis or the Dunnett’ T3 test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the Fisher’s exact test was used for comparison of categorical data between multiple groups. ResultsAll 94 patients with liver injury of unknown origin underwent ultrasound-guided percutaneous liver biopsy after admission， among whom 90 patients （95.7%） had a confirmed diagnosis based on liver biopsy and clinical features. There were 43 patients （45.7%） with AILD， 21 （22.3%） with MAFLD， 15 （16.0%） with DILI， 6 （6.4%） with ALD， 1 （1.1%） with AILD and MAFLD， 1 （1.1%） with hemochromatosis， 1 （1.1%） with Budd-Chiari syndrome， 1 （1.1%） with congenital hepatic fibrosis， and 1 （1.1%） with idiopathic portal hypertension， while 4 patients （4.3%） still had an unknown etiology after liver biopsy. There were significant differences between the patients with top five diagnoses in age （F=4.457， P<0.05） ， body mass index （BMI） （F=3.245， P<0.05）， aspartate aminotransferase （AST） （H=11.128， P<0.05）， gamma-glutamyl transpeptidase （GGT） （H=24.789， P<0.05）， alkaline phosphatase （ALP） （H=26.013， P<0.05）， IgG （H=19.099， P<0.05）， IgM （H=21.263， P<0.05）， AMA-M2 positive rate （P<0.05）， and ANA positive rate （P<0.05）. Compared with the MAFLD group， the AILD group had significantly higher age， AST， GGT， and ALP and a significantly lower BMI； compared with the MAFLD group and the DILI group， the AILD group had significant increases in IgG and IgM； the AILD group had significant increases in the positive rates of AMA-M2 and ANA compared with the other four groups. ConclusionAILD， MAFLD， and DILI are the most common causes in patients with liver injury of unknown origin. Ultrasound-guided percutaneous liver biopsy plays an important role in determining the cause of liver injury of unknown origin， but it is still needed to make a comprehensive analysis based on clinical history， different types of liver injury， laboratory markers， and imaging data.

Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague-Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.