In recent years， significant progress has been made in the standardized diagnosis and treatment of pancreatic cancer in China. From the lack of treatment options and poor drug efficacy at the beginning to the current comprehensive treatment modality integrating surgery， chemotherapy， radiotherapy， immunotherapy， and targeted therapy under multidisciplinary decision-making， the diagnosis and treatment of pancreatic cancer has gradually achieved higher levels of individualization， refinement， and precision. With reference to the latest evidence-based medical data， this article discusses the hot topics in the diagnosis and treatment of pancreatic cancer and explores the future development directions of this field.

The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.

Lipid metabolism,as the basis of life maintenance,is a prerequisite for cell survival,and lipid homeostasis can rapidly respond to metabolic changes in a coordinated manner.In cancers,there is an increase in lipid metabolism in cancer cells to meet the requirements for plasma membrane synthesis and energy production.Abnormal lipid metabolism plays an important role in the progression of primary liver cancer.This article reviews the association between abnormal lipid metabolism and primary liver cancer,in order to find targets for the prevention and treatment of primary liver cancer.

Objective:To discuss the effect of azathioprine(AZA)on ferroptosis in spermatocytes of the mice induced by reduced glutathione(GSH)peroxidase 4 inhibitor RSL3,and to clarify the potential mechanism.Methods:The spermatogonia GC-2 cells of the mice were randomly divided into control group(no treatment),RSL3 group(treated with 10 nmol·L-1 RSL3 for 24 h),RSL3+ferroptosis inhibitor(Ferrostatin-1,Fer-1)group(treated with 10 nmol·L-1 RSL3 for 24 h+2 μmol·L-1 Fer-1 for 12 h),RSL3+low dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+5 μmol·L-1 AZA for 12 h),RSL3+medium dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+10 μmol·L-1 AZA for 12 h),and RSL3+high dose of AZA group(treated with 10 nmol L-1 RSL3 for 24 h+20 μmol·L-1 AZA for 12 h).The MTT method was used to detect the activities of the GC-2 cells in various groups after treated with different concentrations of AZA and RSL3;the GSH and GSSG levels in the GC-2 cells were detected by GSH and oxidized glutathione(GSSG)detection kits;the malondialdehyde(MDA)levels in the GC-2 cells in various groups were detected by MDA detection kit;Western blotting method was used to detect the expression levels of long-chain acyl-CoA synthetase 4(ACSL4),heme oxygenase-1(HO-1),and glutathione peroxidase 4(GPX4)proteins in the cells in various groups;immunofluorescence staining was used to detect the expressions of ACSL4 protein in the cells in various groups.Results:Compared with control group,the differences in activities of the GC-2 cells in 5,10,and 20 μmol·L-1 AZA groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 30 and 40 μmol·L-1 AZA groups were significantly decreased(P＜0.01);therefore,the AZA concentration was selected to be within 20 μmol·L-1.Compared with control group,the differences of the activities of the GC-2 cells in 1,5,and 10 nmol·L-1 RSL3 groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 50,100,500,and 1 000 nmol·L-1 RSL3 groups were significantly decreased(P＜0.05 or P＜0.01);therefore,the RSL3 concentration was set to be within 10 nmol·L-1.The GSH and MDA detection kits results showed that compared with control group,the levels of GSSG and MDA in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the GSH levels were significantly decreased(P＜0.05);compared with RSL3 group,the levels of GSSG and MDA in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased(P＜0.01),while the GSH levels were significantly increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of ACSL4 and HO-1 proteins in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the expression level of GPX4 protein was significantly decreased(P＜0.01);compared with RSL3 group,the expression levels of GPX4 protein in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly increased(P＜0.05),while the expression levels of ACSL4 and HO-1 proteins were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the expression amount of ACSL4 protein in the GC-2 cells in RSL3 group was significantly increased,and compared with RSL3 group,the expression amounts of ACSL4 protein in the cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased.Conclusion:AZA can alleviate the ferroptosis-induced by RSL3 in spermatocytes of the mice.

Objective:To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.Methods:A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.Results:The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion:Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

ObjectiveTo review the ancient and modern literature of Huanglian Ejiaotang and learn about the historical evolution and clinical application， thereby providing a theoretical basis for the modern application of the classical prescription. MethodLiterature in the Chinese Medical Classics Database was retrieved with "Huanglian Ejiaotang" as the keyword. In China National Knowledge Infrastructure （CNKI） and PubMed， "Huanglian Ejiaotang" in Chinese and English was used as the keyword to retrieve literature. The items and modern clinical application studies related to the prescription， medicine， dosage， syndrome， and treatment of Huanglian Ejiaotang were selected and recorded. The inclusion and exclusion criteria were used to screen out literature. The information about the dynasty， book title， function， and indication was integrated to understand the history， evolution， and clinical application of Huanglian Ejiaotang. ResultFinally， 89 ancient books were included with 111 items. Huanglian Ejiaotang was initially recorded in ZHANG Zhongjing's Treatise on Cold Damage and Miscellaneous Diseases in the Han dynasty. It was composed of five herbs， namely Coptidis Rhizoma， Scutellariae Radix， Paeoniae Radix Alba， Asini Corii Colla， and egg yolk. With the change of historical dynasties， the composition， origin basis， dosage， and preparation method of Huanglian Ejiaotang all changed， but the changes in the processing were not obvious， which was basically consistent with Treatise on Cold Damage and Miscellaneous Diseases. In addition， 48 studies were included to analyze the clinical application of Huanglian Ejiaotang， which was mainly used for insomnia， anxiety， depression， diabetes， and so on. ConclusionAccording to the ancient and modern literature， the origin basis， dosage， processing， decoction， administration， and other content of Huanglian Ejiaotang are consistent with Treatise on Cold Damage and Miscellaneous Diseases. The present clinical application has expanded the usage scale of the ancient record， which promotes the innovation and development of the classic prescription and provides references for later research， development， and accurate application.

Pancreatic cystic neoplasm (PCN) is characterized by cystic degeneration with a low incidence. With the development of imaging technology and the popularization of screening, the detection rate of this disease has been increasing in recent years, especially in the elderly population. Due to the multiple subtypes of PCN, difficult differential diagnosis, and the potential risk of malig-nant transformation, the formulation of reasonable diagnosis and treatment strategy is the key to treat PCN. Although many clinical guidelines have been released, the diagnosis and treatment strategies of PCN are still controversial. Elderly patients are generally weak, some with serious comorbidities, and have poor tolerance to surgery. In the process of diagnosis and treatment, clinicians need to pay special attention, carefully evaluate and weigh the advantages and disadvantages, so as to make the best plan for treatment. Based on the current guidelines and clinical experience, the authors summarize the diagnosis, surgical indications, and the whole-course management strategies of elderly patients with PCN, in order to provide suggestions for the diagnosis and treatment of this disease.

Objective:To investigate the risk factors for hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection.Methods:Patients with chronic HCV infection who were treated in Tianjin Second People′s Hospital from January 2012 to April 2019 were enrolled and the incidence of new HCC was retrospectively analyzed. Cox proportional hazards model was used to analyze the risk factors for HCC.Results:Among the 644 patients with chronic HCV infection, 421 cases (65.4%) had chronic hepatitis C(CHC), 223 cases (34.6%) had hepatitis C cirrhosis, and 34 cases had new HCC. No patient without cirrhosis developed HCC. Cox proportional hazards multivariate analysis showed that Child-Pugh grade B or above (hazard ratio ( HR)=6.050, 95% confidence interval ( CI) 2.658 to 13.771, P<0.001), drinking history ( HR=3.077, 95% CI 1.428 to 6.634, P=0.004), family history of cancer ( HR=2.376, 95% CI 1.155 to 4.888, P=0.019), age≥60 years old ( HR=3.301, 95% CI 1.563 to 6.974, P=0.002), controlled attenuation parameter>292 dB/m ( HR=3.842, 95% CI 1.543 to 9.565, P=0.004) were risk factors for HCC. Conclusions:Patients with CHC, especially cirrhosis, are still at risk of HCC post-SVR. HCC monitoring should be strengthened for individuals over 60 years of age, Child-Pugh grade B or above, with severe fatty liver disease, drinking history or family history of malignancy.

OBJECTIVE To investigate the risk factors for tigecycline -induced hypofibrinogenaemia by systematic review . METHODS The literature about risk factors for tigecycline -induced hypofibrinogenaemia were retrieved from English databases （PubMed，Cochrane Library ，Embase，Web of Science ）and Chinese databases （CNKI，Wanfang Database ，VIP，CBM）during the inception to Feb . 5th，2022. At the same time ，the unpublished clinical trial data were additionally searched . After the quality evaluation of the included literature was carried out by adopting the Castle -Ottawa Scale （NOS），data were extracted from the literature that met the inclusion criteria ，and Meta -analysis was conducted by using RevMan 5.3 software. RESULTS Finally，8 literature were selected ，with a total of 1 374 cases，including 706 cases in the trial group and 668 cases in the control group . There were 4 Chinese and 4 English literature ，all of which were case control studies published between 2017-2021. Meta-analysis showed that the risk factors for tigecycline -induced hypofibrinogenaemia were age [OR＝1.04，95%CI（1.02，1.06），P＝0.000 5]，baseline fibrinogen level [OR＝0.54，95%CI（0.42，0.69），P＜0.000 01]，abdominal infection （sensitivity analysis ）[OR＝9.43，95%CI（4.24， 20.95），P＜0.000 01]，dose each time [OR＝2.87，95%CI（2.04，4.02），P＜0.000 01]，medication time [OR＝1.10，95%CI（1.00， 1.22），P＝0.04]. CONCLUSIONS Advanced age ，low baseline fibrinogen levels ，abdominal cavity infection ，relative high dose each time and slightly long medication time are potential risk factors for tigecycline -induced hypofibrinogenaemia . If the above risk factors exist ，it is suggested to pay close attention to the occurrence of hypofibrinogenaemia in the course of tigecycline administration.