The effect of combined chemoradiotherapy versus chemotherapy alone on the survival of ⅣB stage esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the survival benefit of radiotherapy on the basis of systemic treatment for stage ⅣB esophageal squamous cell carcinoma (ESCC).Methods:Based on inclusion and exclusion criteria, we collected the treatment information of 298 patients with newly diagnosed stage ⅣB ESCC admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2016 to February 2021. All patients were divided into two groups based on treatment: early radiotherapy intervention group (CRT group, n=197) and salvage radiotherapy intervention or no intervention group (CT group, n=101). Propensity score matching (PSM) was used to balance baseline characteristics between two groups. Kaplan-Meier method was used to calculate the survival rate and log-rank was used to test the difference. Cox model was used to analyze the multivariate prognosis. Results:In the CRT and CT groups, the objective response rate (ORR) and disease control rate (DCR) were 52.8% vs. 31.5%( P=0.006) and 98.9% vs. 85.4%( P=0.001) respectively, and the 1-, 2- and 3-year survival rates were 74.2% vs. 52.8%、31.5% vs. 10.1% and 15.7% vs. 2.2%, respectively. Median progression-free survival (PFS) was 8.5 months (95% CI: 6.7-10.3 months) vs. 4.4 months (95% CI: 3.5-5.3 months)( P<0.001). Median overall survival (OS) were 17.1 months (95% CI: 14.9-19.3 months) vs. 12.7 months (95% CI: 8.0-17.4 months)( P<0.001). The difference of adverse reactions was mainly in hematology. Conclusions:For newly diagnosed stage ⅣB patients with ESCC, radiotherapy should be combined with systemic therapy as early as possible. It yields longer PFS and OS, and effectively improves dysphagia. Adverse reactions are tolerated. Further validation is recommended in larger prospective studies.

Current status and controversy of adjuvant radiotherapy after radical resection of esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Currently, the value of adjuvant therapy after radical resection of esophageal squamous cell carcinoma remains elusive. Some studies have reported that radiotherapy can improve the locoregional control rate and overall survival of patients. However, the design of radiotherapy target area, intervention time and dose of radiotherapy are controversial. In this article, literature review was conducted and the current status and controversy of adjuvant radiotherapy after radical resection of esophageal squamous cell carcinoma were reviewed.

A case of keratitis-ichthyosis-deafness syndrome complicated by cutaneous squamous cell carcinoma：mutation analysis of the GJB2 gene and literature review / 中华皮肤科杂志

Objective To analyze mutations in the GJB2 gene in a Chinese patient with keratitis-ichthyosis-deafness (KID)syndrome complicated by cutaneous squamous cell carcinoma. Methods Clinical data were collected from a patient with KID syndrome complicated by cutaneous squamous cell carcinoma. Peripheral blood samples were obtained from the patient and her parents, and DNA was extracted from these blood samples. PCR was performed to amplify the exon 2 of the GJB2 gene followed by direct DNA sequencing. Results A mutation (c.148G > A)was identified at position 148 in exon 2 of the GJB2 gene, which caused a codon change from GAC to AAC and resulted in the substitution of aspartate by asparagine at position 50 in the connexin26 (Cx26)protein (p.Asp50Asn). Inaddition,anothermutation(c. 79G > A), which led to the substitution of valine by isoleucine at codon 27 in Cx26 (p.Val27Ile), was found at position 79 in exon 2 of the GJB2 gene. Neither of the two mutations was detected in the patient′s parents. Literature review revealed that 13 cases of KID syndrome complicated by cutaneous squamous cell carcinoma had been reported in abroad, and the mutation c.148G > A was detected in the GJB2 gene in all the 7 cases finally diagnosed by gene sequencing. Conclusion GJB2 gene mutations may be responsible for the clinical phenotype of KID syndrome in this Chinese patient, and the mutation c.148G > A may be related to the development of cutaneous squamous cell carcinoma.

Papillon-Lefèvre syndrome: a case report and mutation analysis of the cathepsin C gene / 中华皮肤科杂志

Objective To analyze mutations in the cathepsin C (CTSC) gene in a patient with Papillon-Lefèvre syndrome (PLS).Methods Clinical data were collected from a patient with PLS.Two milliliters of venous blood samples were obtained from the patient,his parents and 100 unrelated healthy controls separately.DNA was extracted from these blood samples,and PCR was performed to amplify all the 7 exons of the CTSC gene followed by direct DNA sequencing.Results Two heterozygous mutations were observed in the CTSC gene of the patient.One was a novel mutation c.824C ＞ T at position 824 in the exon 6,which resulted in a substitution of ACC (threonine) by ATC (isoleucine) at codon 275 (p.T275I).The other one was the mutation c.1040A ＞ G at position 1040 in the exon 7,causing the substitution of TAT (tyrosine) by TGT (cysteine) at codon 347 (p.Y347C).His father and mother carried the heterozygous mutation c.824C ＞ T and c.1040A ＞ G respectively.Neither of the two mutations was observed in the 100 healthy controls.Conclusions CTSC mutations are responsible for the clinical phenotype of PLS.Identification of the c.824C ＞ T mutation extends the spectrum of mutations in the CTSC gene and provides a basis for genetic diagnosis of PLS.

Benign familial chronic pemphigus in a family: a clinical survey and mutation analysis of ATP2C1 gene / 中华皮肤科杂志

Objective To report a Chinese pedigree with benign familial chronic pemphigus (BFCP),and to screen mutations of ATP2C 1 gene in this family.Methods A 39-year-old male patient with BFCP andhis family members underwent a clinical investigation.Blood samples were collected from all the members in this family and from 50 unrelated healthy controls.Genomic DNA was extracted from the blood samples,and PCR was performed to amplify all the 28 exons and flanking sequences of the ATP2C1 gene followed by DNA direct sequencing.The resulted DNA sequences were compared with the reported sequences of APT2C1 gene in Genbank (Number:NM_014382.2 and NC_000003.9).Results There were 24 family members in the four-generation pedigree,with 8 members affected by BFCP.A single-nucleotide substitution,c(1696C→T),in exon 17 of the ATP2C1 gene was identified in all of the members with BFCP,but not in unaffected third-or second-generation members or unrelated healthy controls.This substitution was also found in 1 out of 4 family members of fourth-generation.Conclusions The nonsense mutation c(1696C→T) in the ATP2C1 gene,is likely to be responsible for BFCP in this Chinese four-generation pedigree.The underage family member of fourth-generation who carried the mutation c(1696C→T) but had no clinical symptoms of BFCP,should be closely followed.

Heat shock protein 110 improves the immunological effect of an altered peptide ligand of human papilloma virus type 16 E711-20 peptide / 中华皮肤科杂志

ObjectiveTo investigate the adjuvant effect of heatshock protein 110(HSP110) on the immune responses induced by an altered peptide ligand of human papilloma virus type 16 E711-20 peptide (HPV16E711-20).Methods The complex of HSP110 and an altered peptide ligand of HPV16E711-20 was constructed in vitro.Fifteen 6-week-old C57BL/6 female mice were randonly and equally divided into 3 groups,including complex group,ligand group,and phosphate buffered solution (PBS) group,to receive intraperitoneal immunization with the complex (100 μg),peptide (10 μg),and PBS (100 μl) respectively.Immunization was carried out with an interval of 2 weeks for 2 times.Two weeks after the last immunization,the mice were sacrificed followed by the isolation of splenocytes.MTT assay was performed to evaluate the proliferation activity of splenocytes,intracellular staining for interferon(INF)-γ to detect cytotoxic T lymphocytes (CTLs),standard chromium-51 (51Cr) release assay to estimate the lethal effect of specific CTLs on target cells.Statistical analysis was performed by using t test with SPSS 10.0 software.Differences were considered as statistically significant when the P value was less than 0.05.ResultsA significant increase was observed in the proliferation index ( 1.87 ± 0.122 vs.0.32 ± 0.071,t =4.01,P ＜ 0.01 ) of,and percentage of CD8+IFN-γ+ T lymphocytes(3.9％ vs.0.4％,t =3.88,P ＜ 0.01 ) among splenocytes from the complex group compared with the ligand group.At the effector-to-target ratio of 100 ∶ 1,50 ∶ 1,25∶ 1 and 12.5 ∶ 1,the death rate of target cells was 54.7％,72.2％,61.5％ and 39.8％ respectively after incubation with CTLs from the compleximmunized mice,higher than that from the ligand-immunized mice (35.2％,49.3％,28.1％,17.4％,respectively).ConclusionHSP110 could enhance the immunological effect of the altered peptide ligand of HPV16E711-20,and can serve as an immunological adjuvant.

Determination of human papillomavirus types in giant condyloma acuminatum / 中华皮肤科杂志

ObjectiveTo determine the genotypes of human papillomavirus(HPV) in patients with giant condyloma acuminatum.MethodsSixty-seven outpatients with giant condyloma acuminatum collected from January 2007 to January 2010 were included in this study.Lesional specimens were obtained from these patients.The genotypes of HPV were determined by flow-through hybridization and gene chip assay.ResultsOf the 67 cases of giant condyloma acuminatum,63 (94.02％) were positive for HPV DNA.Among the HPV DNA-positive specimens,84 (60.87％) harbored low risk types of HPV,54 (39.13％) high risk types of HPV.Type 6 and 11were the predominant low risk HPV types,while type 16 and 18 were the major high risk HPV types.

Different courses of topical tacrolimus 0.1％ ointment for facial corticosteroid-dependent dermatitis: a clinical observation / 中华皮肤科杂志

Objective To evaluate the clinical efficacy and safety of different courses of topical tacrolimus 0.1％ ointment in facial corticosteroid-dependent dermatitis and to observe the rebound in patients after treatment with these regimens.Methods A total of 104 patients with facial corticosteroid-dependent dermatitis were randomly divided into 3 groups to be treated with topical tacrolimus 0.1％ ointment twice daily for 4,8 and 16 weeks respectively.The patients were followed up every 2 weeks within the early 4 weeks of treatment and every 4 weeks thereafter.The rebound phenomena was observed in patients on week 4 after the withdrawal of tacrolimus.Results Finally,90 patients completed this trial,including 32 patients in the 4-week group,29 patients in the 8-week group and 29 patients in the 16-week group.No significant differences were observed between the 4-,8- and 16-week groups in the total reponse rate (75.00％,82.76％,86.21％,respectively,x2 =1.35,P ＞ 0.05).The rebound rate in the 16-week group significantly differed from that in the 4- and 8-week group (20.69％ vs.46.88％ and 41.38％,both P＜ 0.05),while no statistical difference was noted between the 4- and 8-week groups.Local burning and itching were reported in 31.73％ of these patients,and all of these irritant reactions occurred within the first week of treatment.Conclusions Topical tacrolimus 0.1％ ointment is safe and effective for the treatment of facial corticosteroid-dependent dermatitis.The total response rate does not increase with the extended treatment course,and 4 weeks of treatment is enough for the marked and stable improvement of facial corticosteroid-dependent dermatitis,but the rebound rate is likely to be reduced by extended treatment course.

Immunogenicity of the immunodominant cytotoxic T lymphocyte epitope E749-57 in HPV16 oncoprotein E7 chaperoned by HSP110 / 中华皮肤科杂志

Objective To investigate the immunogenicity of immunodominant cytotoxic T lymphocyte epitope E749-57 of human papilloma virus (HPV) 16 oncoprotein E7 chaperoned by heat shock protein (HSP)110. Methods Mouse HSP110 gene was cloned into prokaryotic expression vector pQE-80L for the expression of HSP110 protein, which was purified using Ni-NTA column. SDS-PAGE and Western-blot were conducted to confirm the purified mHSP110 protein, which was subsequently incubated with E749-57 peptide under heat shock condition, and high-performance liquid chromatography (HPLC) was used to evaluate the binding efficiency of the recombinant protein and E749-57 peptide. Twenty mice were divided into 4 groups to be immunized with mHSP110 protein, E749-57 peptide, mHSP110-E749-57 complex and phosphate buffered saline (PBS),respectively. Two weeks after the last immunization, spleen cells were collected from the immunized mice and divided into 2 parts: one were stimulated by E749-57 peptide followed by the detection of CD8+ INF-γ+ T cells with flow cytometry; the other one were subjected to MTT analysis for the estimation of cell proliferation. The mHSP110-E749-57 complex was also used to immunize TC-1 tumor bearing mice to observe its anti-tumor effect.Results The full-length 2577 bp-sized mHSP110 gene was amplified from mouse liver cDNA and cloned into pQE-80L vector. Direct sequencing confirmed the correctness of the cloning. SDS-PAGE and Western-blot demonstrated the successful purification of mHSP110. HPLC assay showed that the purified mHSP110 protein could bind with E749-57 to form a relatively stable protein complex. The percentage of IFN-γ+ CD8+ T cells in and proliferation index of spleen cells from the complex-immunized mice were statistically higher than those from the other 3 groups of mice. Moreover, the complex could obviously inhibit the growth of TC-1 tumor in mice. Conclusion The mHSP110-E749-57 complex could enhance the generation of specific cytotoxic T lymphocytes and exert anti-tumor effects in mice.

The Role of CpG Sequences in the Induction of Anti-dsDNA Antibodies / 中华皮肤科杂志

Objective To investigate the effect of CpG sequences on t he induction of anti-dsDNA antibodies and the possible mechanism. Methods Usin g a synthetic oligodeoxynucleotide (CpG-ODN) containing CpG as an adjuvant, nati ve calf thymus DNA (nCTDNA) was used as the mimic self antigen to immunize norma l BALB/c mice. About one week after immunization, anti-dsDNA antibodies were tes ted by ELISA using nCTDNA and native Escherichia coli DNA (nECDNA) as test antig ens. Results The levels of anti-dsDNA antibodies and cytokines including IL-6, IL-12, IFN- but the binding abilities were different significantly. Conclusion The CpG motif can promote the product ion of cross-reactive anti-dsDNA antibodies in normal mice.

The Pathology of Skin Lesions with Different Clinical Manifestations of Plane Warts / 中华皮肤科杂志

Objective To find out the pathologic changes and possible influencing factors in the process of spontaneous regression of plane warts.Methods One hundred and five lesional specimens taken from patients with plane warts were observed microscopically.Results The histologic features indicated slight hyperkeratosis,acanthosis and ballooning degeneration of keratinocytes in stable lesions;a combination of tower-peak shaped hyperkeratosis,cuneate hypergranulosis and ballooning degeneration in progressively increasing lesions;and infiltration of lymphocytes and necrosis of keratinocytes in inflammatory icthing lesions.Conclusions Specific cell-mediated immunity against keratimocytes may be involved in the process of regression of plane warts.There is a positive correlation between the activity of skin lesions and the induction of cellular immunity.