OBJECTIVE: To explore the clinical presentation and genetic etiology of a case with Xeroderma pigmentosum in conjunct with basal cell carcinoma and melanoma. METHODS: A male patient with Xeroderma pigmentosum treated at Xinxiang Central Hospital in October 2022 was selected as study subject. Whole exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing of his family members. This study was approved by the Ethics Committee of the hospital (Ethics No.: 2021-167). RESULTS: Magnetic resonance imaging showed that the patient has a solid soft tissue mass in the anterior and lower part of his right eyeball and a small nodule on the left nasal wing. Histopathological biopsy showed that the periocular tumor was basal cell carcinoma in conjunct with malignant melanoma, and the nasal wing tumor was basal cell carcinoma. WES and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XPC gene, namely c.2391delT (p.F797Lfs*11) and IVS1+1G>A, which were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were rated as likely pathogenic (PVS1+PM2_Supporting+PM3) and pathogenic (PVS1+PM2_Supporting+PM3+PP5), respectively. The c.2391delT variant was unreported previously. Bioinformatic analysis suggests that it could significantly affect the tertiary structure of XPC protein. CONCLUSION The c.2391delT(p.F797Lfs*11) and IVS1+1G>A compound heterozygous variants probably underlay the pathogenesis in this patient. The detection of the novel variant has enriched the mutational spectrum of the XPC gene.
Humans ; Male ; Xeroderma Pigmentosum/genetics* ; Basal Cell Carcinoma/genetics* ; DNA-Binding Proteins/genetics* ; Melanoma/genetics* ; Mutation ; Skin Neoplasms/genetics* ; Middle Aged ; Exome Sequencing ; Pedigree

Objective To investigate the predictive value of serum oncogene[proliferation-related gene(C-myc),transformation gene(N-ras),silk/threonine kinase 1(PLK1),fibroblast growth factor 2(FGF2)]protein levels in patients with hepatitis B associated hepatocellular carcinoma(HCC)after hepatic arterial chemoem-bolization(TACE).Methods A total of 127 patients with hepatitis B-associated hepatocellular carcinoma ad-mitted to a hospital from July 2016 to January 2021 were selected and divided into death group and survival group according to the follow-up results.The serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels were determined by double-antibody sandwich enzyme-linked immunosorbent assay.Univariate and multivari-ate Cox analysis were used to analyze the risk factors of serum oncogene C-myc,N-ras,PLK1 and FGF2 pro-tein levels in patients with hepatitis B-associated hepatocellular carcinoma after TACE.The receiver operating characteristic curve was used to evaluate the prognostic value of the serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels,and the patients were divided into high expression group and low expression group ac-cording to the corresponding cutoff value.Kaplan-Meier survival curve was used to evaluate the prognosis of different serum oncogene C-myc,N-ras,PLK1 and FGF2 protein level.Results Multivariate Cox regression a-nalysis indicated that TNM stage Ⅲ to Ⅳ(HR=2.998,95％CI:1.239-7.257),portal vein metastasis(HR=3.737,95％CI:1.941-7.193),abdominal metastasis(HR=3.482,95％CI:1.709-7.097),Child-Pugh grade B(HR=2.587,95％CI:1.045-6.406),high serum oncogene C-myc protein level(HR=1.224,95％CI:1.090-1.374),high serum oncogene N-ras protein level(HR=1.218,95％CI:1.097-1.353),high serum oncogene PLK1 protein level(HR=1.237,95％CI:1.110-1.379)and high serum oncogene FGF2 protein level(HR=1.141,95％CI:1.060-1.228)were independent risk factors for the prognosis of hepatitis B-asso-ciated hepatocellular carcinoma patients after TACE(all P＜0.05).The overall survival rate of low expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level was significantly higher than that of high expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level,the difference was statistically significant(all P＜0.001).Conclusion Serum oncogene C-myc,N-ras,PLK1,FGF2 protein levels have predic-tive value for the prognosis of patients with HBV-related liver cancer after TACE.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Objective To investigate the effect of dexmedetomidine ( Dex) combined with ropivacaine in brachial plexus block ( BPB) on serum basic fibroblast growth factor ( bFGF) levels of upper limb fracture patients in the perioperative period. Methods 80 patients ( ASA gradeⅠ~Ⅱ) scheduled for selective upper extremity surgery were randomly divided into the dexmedetomidine combined with ropiva-caine group ( RD group) and the ropivacaine group ( R group) with 40 patients in each group. BPB was performed at the point of 2 cm below coracoid directed by nerve stimulator. Ropivacaine (200 mg) was diluted into 40 mL in group R and ropivacaine (200 mg) +1 μg/kg dexmedetomidine were diluted into 40 mL in group RD. Drew 5 mL blood at T0~T4 points respectively,and serum bFGF concentration were determined. Results Compared with group R,MAP and HR at T1~T3 points were significantly lower in group RD (P<0. 05). SpO2 in the two groups at each point had no statistical significance (P>0. 05). Compared with T0 points,bFGF concentration were increased in two groups at T1~T4 points (P<0. 05),and it was higher in group RD compared with group R (P<0. 05). Conclusion Dex combined bra-chial plexus block promote the secretion of bFGF more than simple brachial plexus block,which is conducive to fracture healing after opera-tion,but it should be cautious to apply for patients with bradyarrhythmia.

Objective: To develop a scoring system for estimating advanced colorectal neoplasm risk in average-risk population in southern Jiangsu province, and to evaluate its screening efficiency. Methods: An average-risk population of colorectal neoplasm in southern Jiangsu province, who underwent colonoscopy, was included in this study. All participants were asked to complete a questionnaire on demographic characteristics, medical history, smoking, alcohol consumption, dietary intake, and other factors that may be associated with advanced neoplasms. A multivariable logistic regression method was used to identify independent predictors of advanced neoplasms. A scoring system was developed from the logistic regression model by using a regression coefficient-based scoring method, and then was internally validated. The screening efficiency of the scoring system was assessed by its calibration, discrimination, and accuracy. Results: A total of 905 average-risk participants were included in this study. The scoring system comprised 5 variables (age, sex, coronary artery disease, egg intake, and defecation frequency), with scores ranging from 0 to 10. The system had good calibration (P= 0.205) and good discrimination (area under the receiver operating characteristic curve = 0.75, 95% confidence interval: 0.69-0.82). If score 2.5 was used as the screening cut-off value, the sensitivity, specificity, accuracy rate, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were 93.8%, 47.6%, 50.1%, 9.1%, 99.3%, 1.79, and 0.13, respectively. Among the participants with low-risk (0-2) or high-risk (>2) scores, the risks of advanced neoplasms were 0.7% and 9.1% (P<0.001), respectively. If colonoscopy was used only for persons with high risk, 93.8% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 45.4%. Conclusion: The scoring system in this study has satisfactory screening efficiency and can be used for preliminary screening of advanced colorectal neoplasms in average-risk population in southern Jiangsu Province.