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Background: The frequency of acute hypertriglyceridemic pancreatitis (AHTGP) is increasing worldwide. AHTGP may be associated with a more severe clinical course and greater mortality than pancreatitis caused by other causes. Early identification of patients with severe inclination is essential for clinical decision-making and improving prognosis. Therefore, we first developed and validated a risk prediction score for the severity of AHTGP in Chinese patients., Aim: To develop and validate a risk prediction score for the severity of AHTGP in Chinese patients., Methods: We performed a retrospective study including 243 patients with AHTGP. Patients were randomly divided into a development cohort ( n = 170) and a validation cohort ( n = 73). Least absolute shrinkage and selection operator and logistic regression were used to screen 42 potential predictive variables to construct a risk score for the severity of AHTGP. We evaluated the performance of the nomogram and compared it with existing scoring systems. Last, we used the best cutoff value (88.16) for severe acute pancreatitis (SAP) to determine the risk stratification classification., Results: Age, the reduction in apolipoprotein A1 and the presence of pleural effusion were independent risk factors for SAP and were used to construct the nomogram (risk prediction score referred to as AAP). The concordance index of the nomogram in the development and validation groups was 0.930 and 0.928, respectively. Calibration plots demonstrate excellent agreement between the predicted and actual probabilities in SAP patients. The area under the curve of the nomogram (0.929) was better than those of the Bedside Index of Severity in AP (BISAP), Ranson, Acute Physiology and Chronic Health Evaluation (APACHE II), modified computed tomography severity index (MCTSI), and early achievable severity index scores (0.852, 0.825, 0.807, 0.831 and 0.807, respectively). In comparison with these scores, the integrated discrimination improvement and decision curve analysis showed improved accuracy in predicting SAP and better net benefits for clinical decisions. Receiver operating characteristic curve analysis was used to determine risk stratification classification for AHTGP by dividing patients into high-risk and low-risk groups according to the best cutoff value (88.16). The high-risk group (> 88.16) was closely related to the appearance of local and systemic complications, Ranson score ≥ 3, BISAP score ≥ 3, MCTSI score ≥ 4, APACHE II score ≥ 8, C-reactive protein level ≥ 190, and length of hospital stay., Conclusion: The nomogram could help identify AHTGP patients who are likely to develop SAP at an early stage, which is of great value in guiding clinical decisions., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To determine the lethiferous effects of a recombinant vector carrying thymidine kinase (TK) suicide gene on 2.2.15 cells and the possible self-modulating mechanism., Methods: A self-modulated expressive plasmid pcDNA3-SCITK was constructed by inserting the fragments carrying hepatitis B virus antisense-S (HBV-anti-S) gene, hepatitis C virus core (HCV-C) gene, internal ribosome entry site (IRES) element of HCV and TK gene into the eukaryotic vector pcDNA3, in which the expression of TK suicide gene was controlled by the HBV S gene transcription. 2.2.15 cells that carry the full HBV genome and stably express series of HBV antigen were transfected with pcDNA3-SCITK or vector pcDNA3-SCI which was used as the mock plasmid. The HepG2 cells transfected with pcDNA3-SCITK were functioned as the negative control. All the transfected cells were incubated in DMEM medium supplemented with 10 microg/ml. of ganciclovir (GCV). The HBsAg levels in the supernatant of cell culture were detected by ELISA on the 1st, 3rd and 6th day post-transfection. Meanwhile, the morphology of transfected cells was recorded by the photograph and the survival cell ratio was assessed by the trypan blue exclusion test on the 6th day post-transfection., Results: The structural accuracy of pcDNA3-SCITK was confirmed by restriction endonuclease digestion, PCR with specific primers and DNA sequencing. The HBsAg levels in the supernatant of transfected 2.2.15 cell culture were significantly decreased on the 6th day post-transfection as compared with that of the mock control (P<0.05). The lethiferous effect of pcDNA3-SCITK expression on 2.2.15 cells was initially noted on the 3rd day after transfection and aggravated on the 6th day post transfection, in which the majority of transfected 2.2.15 cells were observed shrunken, round in shape and even dead. With assessment by the trypan blue exclusion test, the survival cell ratio on the 6th day post transfection was 95% in the negative control and only 11% in the experimental group., Conclusion: The results indicate that suicide gene expression of pcDNA3-SCITK can only respond to HBV-S gene transcription, which may be potentially useful in the treatment of HBV infection and its related liver malignancies.

AIM:To explore the status of extrahepatic hepatitis C virus (HCV) infection and replication in hepatitis C patients,and its potential implication in HCV infection and pathogenicity.METHODS:By reverse-transcriptase poly-merase chain reaction (RT-PCR),in situ hybridization (ISH) and immunohis-tochemistry, HCV RNA, HCV replicative intermediate (minus-strand of HCV RNA), and HCV antigens were detected in 38 autopsy extrahepatic tissue specimens (including 9 kidneys, 9 hearts, 9 pancreas, 5 intestines, 2 adrenal glands, 2 spleens, 1 lymph node, and 1 gallbladder) from 9 hepatitis C patients, respectively; and the status of HCV replication in extrahepatic tissues was studied.RESULTS:By RT-PCR, all 9 patients were positive for HCV RNA in kidney, heart, pancreas, and intestine, but only 6(66.7%) patients were positive for HCV replicative intermediate. HCV RNA and HCV antigens were detected in kidney, heart, pancreas, intestine, adrenal gland, lymph node, and gallbladder in 5(55.6%) and 6(66.7%) patients by ISH and immuno-histochemistry, respectively. HCV RNA and HCV antigens were not detected in these extrahepatic organs in 3(33.3%) patients, although their livers were positive for HCV.HCV replicative intermediate detected by RT-PCR was consistent with HCV RNA and HCV antigens detected by ISH and immunohistochemistry (Kappa =0.42-0.75). HCV RNA and HCV antigens were detected in myocardial cells, epithelial cells of intestinal gladular, interstitial cells of kidney, epithelial cells of tubules and glomerulus, pancreas acinar cells and epithelial cells of pancreatic duct, epithelial cells of mucous membrane sinus of gallbladder, cortex and medulla cells in adrenal gland,and mononuclear cells in lymph node. HCV RNA was also detected in bile duct epithelial cells, sinusoidal cells, and mononuclear cells in liver tissues by ISH.CONCLUSION:HCV can infect extrahepatic tissues, and many various tissue cells may support HCV replication; extrahepatic HCV infection and replication may be of concomitant state in most of patients with hepatitis C. The infected extrahepatic tissues might act as a reservoir for HCV, and play a role in both HCV persistence and reactivation of infection. HCV as an etiologic agent replicating and expressing viral proteins in extrahepatic tissues itself contributes to extrahepatic syndrome associated-HCV infection in a few patients with chronic HCV infection.

AIM:To detect the expression of caspase 3 gene in primary human hepatocellular carcinoma (HCC) and investigate its relationship top21(WAF1) gene expression and HCC apoptosis.METHODS:In situ hybridization was employed to determine caspase 3 and p21(WAF1) expression in HCC.In situ end-labeling was used to detect hepatocytic apoptosis in HCC.RESULTS:Twenty-one of 39 (53.8%) cases of HCC were found to express caspase 3 transcripts, while 46.2% of HCC failed to express caspase 3.Non-cancerous adjacent liver tissues showed more positive caspase 3(87.5%, 7/8) as compared with HCC (p < 0.05). The expression of caspase 3 is correlated with HCC differentiation, 72.2% (13/18) of moderately to highly differentiated HCC showed caspase 3 transcripts positive, while only 38.1% of poorly differentiated HCC harbored caspase 3 transcripts (italic>p < 0.05). No relationship was found between caspase 3 expression and tumor size or grade or metastasis, although 62.5% (5/8) of HCC with metastasis were caspase 3 positive and a little higher than that with no metastasis (51.6%, p> 0.05). Expression of caspase 3 alone did not affect the apoptosis index (AI) of HCC. The AI was 7.12 in caspase 3 positive tumors (n = 21), while in caspase 3-negative cases (n = 18) 6.59 (italic>p > 0.05). Expression of caspase 3 clearly segregated with p21(WAF1) positive tumors as compared with p21(WAF1) negative cases (16 of 23, 69.6% versus 5 of 16, 31.3%) with statistical significance (p = 0.017).In the cases with positive caspase 3 and negative p21(WAF1), the AI was found slightly higher, but with no statistical significance, than that with expres-sion of p21(WAF1) and caspase 3 (7.21 vs 6.98 , p>0.05).CONCLUSION:Loss of caspase 3 expression may contribute to HCC carcinogenesis, although the expression of caspase 3 does not correlate well with cell apoptosis in HCC.p21(WAF1) may be merely one of the inhibitors which can reduce caspase 3 mediated cell apoptosis in HCCs.

AIM:To investigate the clinical features of FADD and TRADD expressions in primary hepatocellular carcinoma (HCC) and to determine their relationship with hepatic apoptosis.METHODS:FADD and TRADD expressions were detected by immunohis-tochemistry and hepatic apoptosis were determined by in situ end-labeling (ISEL).RESULTS:Ten (25.6%) cases of HCC were detected to express FADD protein. The positive rate in HCC is lower than that in non-cancerous adjacent liver tissues (62.5%) (P < 0.05). In those of grade I-II, 8(38.1%) cases were FADD positive, while only 2/18 (11.1%) cases of grade III-had detectable FADD protein (P < 0.05). No relationship was found between FADD expression and other clinical features, such as gender, age, tumor size, different-tiation or metastasis. ISEL positive cells can be seen in all cases of HCC. The hepatic apoptosis was associated with FADD expression as more apoptotic cells were detected in those cases which had moderately to strongly positive FADD, as compared with negative or weak positive FADD cases (P < 0.05). No relationship was found between FADD expression and hepatic apoptosis in non cancerous adjacent liver tissues. Fifteen of 39 (38.5%) cases of HCC were found positive for TRADD prote-in, and similar positive rate (37.5%) in non-cancerous adjacent liver tissues (P > 0.05). The expression of TRADD is correlated with HCC differentiation, as only 22.2% of moderately to highly differentiated HCC showed positive TRADD protein, while as high as 52.4% of poorly differentiated HCC had TRADD (P < 0.05). No relationship was found between TRADD expression and gender, age, tumor size or grade or metastasis, although 42.9% of HCC of grade I/II showed positive TRADD which was slightly higher than that of grade III/IV (33.3%,P>0.05). Hepatic apoptosis was not related to TRADD expression in HCC or non-cancerous adjacent liver tissues.CONCLUSION:Loss of FADD expression plays an important role in HCC carcinogenesis, and expression of TRADD also contributes to HCC development. The cell apoptosis in HCC is associated with FADD expression. However, the expression of TRADD does not correlate well with hepatic apoptosis in HCC.

Aim: To study the short and long-term effect of interferon therapy for chronic hepatitis C., Methods: Sixty-eight patients with chronic hepatitis C were treated with interferon (3 × 10(6) IU, im/2 d, for a course of three months) with 1 to 5 courses of treatment and followed for 1.5 to 3 years after the therapy., Results: According to antiviral effect of interferon, 76.5% (52/68) of the cases had a complete response by the end of the first therapy course, while 20.6% (14/68) and 2.9% (2/68) had a partial response or non-response. Over a half of the patients with a complete response (27/52, 51.9%) relapsed within 6 to 10 mo after the first course. Of the original cohort, nineteen patients received two courses of therapy, while one patient received three and another three received five courses of therapy. The follow-up for these patients was between 1.5 to 3 years, at which time 29 (42.7%) of the patients sustained a complete response, with four of them having HCV RNA positive serum, while the others had either a partial (37/68, 2.9%) or non-response., Conclusion: Interferon therapy had a high short-term complete response but a low long-term complete response in the treatment of chronic hepatitis C.