Objective:To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma.Methods:Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed.Results:There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level.Conclusions:CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Objective To investigate the expression of cysteine rich protein 2 binding protein(CSRP2BP)mRNA and estrogen related receptors β(ESRRB)mRNA and protein in cervical cancer tissues and their correlation with epithelial mesenchymal transition(EMT)and clinical prognosis.Methods A total of 106 cervical cancer patients admitted to Yan'an Traditional Chinese Medicine Hospital from March 2018 to March 2020 were selected.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect CSRP2BP mRNA,ESRRB mRNA and EMT related indicators[E-cadherin(E-cad),N-cadherin(N-cad),snail family transcriptional repressor 1(Snail)].Immunohistochemistry was used to detect the CSRP2BP protein and ESRRB protein expression in tissues.Pearson correlation analysis was used to analyze the correlation between CSRP2BP mRNA,ESRRB mRNA and EMT related indicators.Kaplan-Meier curve and COX regression were used to analyze the effect of CSRP2BP mRNA and ESRRB mRNA expression on the prognosis of cervical cancer patients.Results CSRP2BP mRNA(3.14±0.52 vs 1.22±0.21)expression and protein positive rate(86.79%vs 9.43%),ESRRB mRNA expression(2.86±0.31 vs 1.06±0.20)and protein positive rate(92.45%vs 8.49%),N-cad mRNA(3.22±0.43 vs 1.05±0.26)and Snail mRNA(2.67±0.36 vs 0.69±0.17)expression in cancer tissues were higher than those in adjacent tissues,while E-cad mRNA(0.84±0.17 vs 2.15±0.24)expression was lower than that in adjacent tissues,and the differences were statistically significant(t/x2=34.249,127.049;50.234,149.466;44.461,51.204,45.858,all P<0.001).The expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer was positively correlated with N-cad mRNA and Snail mRNA(r=0.663,0.731;0.726,0.715,all P<0.001),and was negatively correlated with E-cad mRNA(r=-0.594,-0.669,all P<0.001).The expression of CSRP2BP mRNA(4.48±0.36,4.21±0.37,4.69±0.33)and ESRRB mRNA(4.48±0.36,4.21±0.37,4.69±0.33)in cervical cancer tissues of patients with FIGO stage Ⅰ B2～Ⅱ A,poor differentiation and lymph node metastasis was higher than that of patients with FIGO stage ⅠA～ⅠB1(2.60±0.44,2.06±0.24),medium and high differentiation(2.43±0.44,2.01±0.25)and no lymph node metastasis(2.53±0.58,2.07±0.26),and the differences were statistically significant(t=16.327,41.135;18.507,36.545;14.501,43.806,all P<0.001).The 3-year overall survival rate of patients with high expression of CSRP2BP mRNA was 66.00%(33/50),which was lower than 89.29%(50/56)in the low expression group,while the 3-year overall survival rate of the high expression group of ESRRB mRNA was 65.38%(34/52),which was lower than 90.74%(49/54)of the low expression group,and the differences were statistically significant(Log rank x2=5.401,11.400,P=0.020,0.001).Multivariate Cox regression analysis showed that,CSRP2BP mRNA high expression(HR=1.327,95%CI:1.097～1.605),ESRRB mRNA high expression(HR=1.322,95%CI:1.108～1.577),FIGO stage Ⅰ B2～Ⅱ A(HR=1.423,95%CI:1.154～1.755),lymph node metastasis(HR=1.363,95%CI:1.095～1.698)and poor differentiation(HR=1.297,95%CI:1.064～1.581)were risk factors affecting the prognosis of cervical cancer patients(all P<0.001).Conclusion The increased expression of CSRP2BP mRNA and ESRRB mRNA in cervical cancer are related to EMT related indicators and adverse clinical and pathological features,and are new tumor markers for prognostic evaluation.

Objective:To investigate the biological effects of acute high-dose radon exposure on mice.Methods:BALB/c male mice aged 6 to 8 weeks were exposed once in an HD-3 ecological radon chamber with an average radon concentration of 7 × 10 5 Bq/m 3 for 10 h. Mice were weighed, their lung tissues and blood samples were collected at 1, 2 and 3 months after exposure. Control groups were set up at the three time points with four mice in each group. For these mice, the lung tissue pathology was observed using hematoxylin-eosin (HE) staining method, routine blood tests were conducted using a hematology analyzer and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the serum and lung tissues were measured using corresponding assay kits. Results:The HE staining result revealed that compared to the control groups, the experimental groups exhibited thickening of alveolar walls and increased infiltration of granulocyte, whose degrees, however, reduced over time and displayed no significant difference at 3 months after exposure. There was no significant difference in body weight or blood routine between the experimental and control groups. The detection result revealed decreased SOD levels in the lung tissues at 2 months after exposure, which were (11.34 ± 1.03) U/mgprot and (9.75 ± 0.71) U/mgprot, respectively for the control and experimental groups ( t = 2.54, P < 0.05). The MDA levels in lung tissue increased at 1 month after exposure, which were(2.30 ± 0.24) and (2.77 ± 0.29) nmol/mgprot, respectively for the control and experimental groups ( t = 2.49, P < 0.05). At 3 months after exposure, the SOD and MDA levels differed insignificantly between the control and experimental groups ( P > 0.05). Conclusions:After acute high-dose radon exposure, the mice suffered damage to the lung tissue, with changes in their oxidative stress indicators being detected. However, these effects gradually diminished at 3 months after exposure. Additionally, acute high-dose radon exposure did not give rise to significant changes in the body weight or routine blood result of the mice.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A 1c (HbA 1c)≥7.0% was the risk factor of mild-NPDR ( OR=1.872, 95% CI 1.055-3.323) and RDR ( OR=4.821, 95% CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR ( OR=1.933, 95% CI 1.112-3.358) and RDR ( OR=1.505, 95% CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction. METHODS: A patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and the candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 26-year-old male, had manifested atypical mental retardation and ejaculatory dysfunction. WES revealed that he has harbored a heterozygous variant of the ARID1B gene, namely c.5776C>T (p.Arg1926X). Sanger sequencing verified that neither of his parents has carried the same variant. The variant has been recorded in the 1000 Genomes, ExAC, gnomAD and ClinVar databases. A search of the dbSNP database suggested that the variant has a population frequency of 0.000 4%. The variant was predicted as deleterious by online software including Mutation Taster, CADD, and MutPred. Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species. Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was predicted to be pathogenic. CONCLUSION The c.5776C>T (p.Arg1926X) variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient. Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.
Male ; Humans ; Adult ; Intellectual Disability/genetics* ; Transcription Factors/genetics* ; Computational Biology ; Gene Frequency ; Genomics ; DNA-Binding Proteins/genetics*

Objective:To critically evaluate and summarize the methodological quality of systematic reviews(SRs)and present objective and important outcomes on the effectiveness of traditional Chinese medicine(TCM)therapies,including Chinese herbal medicine(CHM),acupuncture,and moxibustion,for diarrhea-predominant irritable bowel syndrome(IBS-D).Methods:We conducted a comprehensive literature search for SRs in 7 databases until April 16,2022.Two reviewers independently extracted data and assessed the methodological quality of the reviews according to the Assessing the Methodological Quality of Systematic Reviews 2(AMSTAR-2),the Risk of Bias in Systematic reviews(ROBIS)tool,and the Preferred Reporting Item for Systematic Review and Meta-analysis(PRISMA)statement.The Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)was used to rate the quality of evidence.Results:IBS-D patients included in 12 reviews were diagnosed in accordance with the Rome criteria,9 reviews focused on CHM,2 articles observed moxibustion and heat-sensitive moxibustion,1 article studied acupuncture and CHM.The outcomes of the SRs were the effectiveness rate,the total effectiveness rate,global symptom improvement,and adverse effects.Based on AMSTAR-2,which measures the quality of methodology,all of the included studies were of low or critically low quality.According to the ROBIS tool,10 SRs(83.33％)had a high risk of bias.With the PRISMA checklist,only 3 SRs reached over 90％compliance.Based on GRADE,most evidence was of low quality,and there was a moderate quality of evidence that the effectiveness rate of modified-Tongxie Yaofang was superior to Western medicine in the treatment of IBS-D.Conclusion:Given the suboptimal reporting and methodological quality of existing SRs,more studies are needed to clarify whether TCM therapies are more effective or safe than pharmacological medicine.Future studies should combine evidence-based medicine with TCM research according to the charac-teristics of TCM.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective:To investigate the expression of epigenetic inhibitor polycomb group proteins such as enhancer of zeste homolog 1/2 (EZH1/EZH2), embryonic ectoderm development protein (EED) and suppressor of zeste 12 (SUZ12) in common cutaneous T-cell lymphomas and lymphoproliferative disorders (CTCL/LPD) .Methods:Totally, 93 paraffin-embedded skin samples of CTCL/LPD and 8 of lichen planus were collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College between 2012 and 2019, and subjected to immunohistochemical staining to determine the protein expression of EZH2, EED, SUZ12 and EZH1. Statistical analysis was carried out with SPSS 25.0 software by using chi-square test and Spearman correlation analysis.Results:The 93 cases of CTCL/LPD included 44 cases of mycosis fungoides (MF), 17 natural killer/T cell lymphoma (NK/TCL), 8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL), 8 lymphomatoid papulosis (LyP), 8 hydroa vacciniforme-like lymphoproliferative disorder (HV-like LPD) and 8 cases of subcutaneous panniculitis-like T cell lymphoma (SPTCL). Among the 93 CTCL/LPD cases, 83 (89.2%) were positive for EZH2, 81 (87.1%) for EED, 78 (83.9%) for SUZ12 and 37 (39.8%) for EZH1; among the 8 cases of lichen planus, 1 was positive for EZH2, all were positive for EZH1, and all were negative for EED and SUZ12. The expression of EZH2, EED, SUZ12 and EZH1 in lichen planus samples significantly differed from all the CTCL/LPD samples ( χ2 = 41.75, 39.74, 39.36, 32.83, respectively, all P < 0.001), and from MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL samples separately (α = 0.008 3, all P < 0.001). Meanwhile, the score of EZH2 expression was negatively correlated with that of EZH1 expression in the MF, NK/TCL, PC-ALCL, LyP, HV-like LPD and SPTCL tissues ( rs = -0.60, -0.68, -0.89, -0.74, -0.93, -0.80, respectively, all P < 0.05) . Conclusion:Polycomb group proteins EZH2, EED, SUZ12 and EZH1 are abnormally expressed in CTCL/LPD lesions.

Objective:To investigate the clinical effects of pelvic radiotherapy on improving the patient′s position variability by using stretching exercises before radiotherapy.Methods:The study period was from January 2017 to May 2019. The study subjects were patients with pelvic malignancies who visited Zhejiang Cancer Hospital during this period and needed radiotherapy. A total of 278 patients were divided into study group and control group according to the random number table method, with 139 cases in each group. The study group performed hip joint stretching and rotation exercises before radiotherapy, while the control group had no special intervention. By comparing the changes in the sacral slope angle (SSA) of the patients between the two groups, the position variability during radiotherapy was reflected. The effects of complications, compliance, and degree of benefit were analyzed.Results:The daily compliance of the study group was above 95%. No patients reported adverse events such as dyskinesias and related pain and falls. The SSA change in the study group patients was significantly reduced ( P<0.05). The daily SSA and baseline SCT in the study group were significantly lower ( P<0.05). The average change in the study group was (0.95 ± 0.24)°(0.52°-1.33°), while the average change in the control group was (2.31 ± 1.05)°(1.17°-5.26°),and there was significant difference ( P<0.05). The comparison of the average differences between the treatment days showed that the average change in the study group was (0.96 ± 0.64)°(0.72°-1.28°)and in the control group was (2.09 ± 1.12)°(0.94°-3.28°),and there was significant difference ( P<0.05). Pearson correlation analysis was used to evaluate its correlation to the overall change of each patient. The reliability between the two assessors showed moderately positive correlation ( r=0.52, P=0.18), and there was also a moderately positive correlation in the control group ( r=0.59, P=0.26). The patients in the study group scored (7.12 ± 0.16) scores on the degree of benefit of participating in the study group. Conclusions:The stretching exercise before radiotherapy can effectively reduce the position variability of patients with pelvic radiotherapy, which is beneficial to improve the effect of diagnosis and treatment.