Significance of lysophosphatidic acid receptor 6 in the large-cell transformation of mycosis fungoides and its effect on the proliferation and apoptosis of cutaneous T-cell lymphoma cells / 中华皮肤科杂志

Objective:To determine lysophosphatidic acid receptor 6 (LPAR6) expression in patients with mycosis fungoides (MF) , a variant of cutaneous T-cell lymphoma (CTCL) , and to investigate its role and mechanism of action in the development and prognosis of CTCL.Methods:A total of 110 patients with confirmed MF were collected from Department of Dermatology, Peking University First Hospital from 2011 to 2020, including 24 with large-cell transformation (LCT) and 25 with non-large cell transformation (NLCT) in the discovery cohort, and 24 with LCT and 37 with NLCT in the validation cohort. RNA sequencing and RT-PCR were conducted to determine the LPAR6 expression in patients in the discovery cohort and validation cohort respectively. LPAR6 expression was compared between patients with LCT and those with NLCT, and its effect on the prognosis of patients was evaluated. Two LPAR6-overexpressing CTCL cell lines MyLa and Sz4 were constructed to evaluate the effect of LPAR6 overexpression on proliferative activity of MyLa and Sz4 cells, with the cells normally expressing LPAR6 as the control group; after the treatment with LPAR6-related ligand lysophosphatidic acid (LPA) , 2S-OMPT, adenosine triphosphate (ATP) or adenosine (ADO) , the effects of LPAR6 activation on the proliferative activity and apoptosis of LPAR6-overexpressing MyLa and Sz4 cells were evaluated by the MTS method and flow cytometry respectively. Log-rank test was used for prognostic analysis, and t test or Mann-Whitney U test was used for comparisons between two groups. Results:As RNA sequencing showed, LPAR6 was one of the significantly underexpressed genes in the LCT group in the discovery cohort; in the validation cohort, LPAR6 expression (median[ Q1, Q3]) was significantly lower in the LCT group (204.90[81.90, 512.70]) than in the NLCT group (809.40[417.50, 1 829.20], U= 242.00, P= 0.002) ; in the two cohorts, the underexpression of LPAR6 was significantly associated with increased risk of poor prognosis (both P < 0.01) . Cell proliferation assay showed no significant difference in the proliferative activity of MyLa or Sz4 cells between the LPAR6 overexpression group and control group at 0, 24, 48 and 72 hours during the experiment (all P > 0.05) ; 48 hours after activation of LPAR6 by LPA, 2S-OMPT, ATP and ADO in MyLa cells, the LPAR6 overexpression group showed significantly decreased cellular proliferative activity (1.38 ± 0.01, 1.04 ± 0.01, 1.09 ± 0.03, 1.23 ± 0.01, respectively) compared the control group (1.73 ± 0.04, 1.23 ± 0.01, 1.24 ± 0.01, 1.42 ± 0.03, t= 30.33, 18.38, 4.78, 5.75, respectively, all P < 0.05) , but significantly increased cell apoptosis rate (17.93% ± 0.88%, 17.75% ± 0.35%, 23.97% ± 0.57%, 31.44% ± 0.34%, respectively) compared the control group (3.98% ± 0.03%, 7.81% ± 0.59%, 11.95% ± 0.85%, 12.02% ± 0.48%, t= 15.93, 14.49, 11.74, 33.01, respectively, all P < 0.05) ; 48 hours after activation of LPAR6 by 2S-OMPT and ADO in Sz4 cells, compared with the control group, the LPAR6 overexpression group also showed significantly decreased cellular proliferative activity (2S-OMPT: 1.29 ± 0.04 vs. 1.48 ± 0.01; ADO: 1.27 ± 0.01 vs. 1.51 ± 0.02; both P < 0.05) , but significantly increased cell apoptosis rate (2S-OMPT: 41.70% ± 0.70% vs. 29.35% ± 0.55%; ADO: 37.05% ± 0.15% vs. 24.60% ± 1.00%; both P < 0.05) . Conclusions:LPAR6 was underexpressed in the patients with LCT, and its underexpression was significantly associated with increased risk of poor prognosis. In vitro activation of LPAR6 could inhibit the proliferation of CTCL cells and promote their apoptosis, suggesting that the decrease of LPAR6 expression may be one of the important mechanisms underlying disease progression in patients with LCT.

Correlations between pruritus and CC chemokine ligand 17 in patients with mycosis fungoides / 中华皮肤科杂志

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

Correlation between the expression of androgen receptor mRNA and the long-term tumor-specific and recurrence-free survival rate in patients with T1 bladder cancer / 国际外科学杂志

Objective To investigate the predictive value of androge receptors in stage pT1 non-muscle-invasive bladder cancer.Methods A total of 196 patients with stage pT1 non-muscle-invasive bladder cancer who underwent a transurethral resection of the bladder in Baoji People's Hospital from February 2003 to June 2012 were recruited to carry a retrospective analysis.The mRNA expression of the androge receptors transcript variants 1 (AR1) and 2 (AR2) was measured by quantitative real-time PCR.Spearman's correlation coefficient was used to analysis the correlation of androge receptors mRNA level to KRT5 and KRT20 mRNA.Results Kaplan-Meier analysis indicated that the recurrence-free survival,progression-free survival and cancer specific survival of patients with high AR1 mRNA expression (≥35.47) were significant better than patients with low AR1 mRNA expression (P ＜0.05).Multivariate COX regression analysis revealed that high AR1 mRNA expression was an independent prognostic marker for recurrence-free survival and cancer specific survival (P ＜ 0.05).Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (rs =0.3171,P ＜ 0.001) as well as a negative association with multifocal tumors (rs =0.1478,P ＜ 0.05).Conclusion Androge receptors mRNA expression can predict recurrence-free survival and cancer specific survival in patients with stage T1 nonmuscle-invasive bladder cancer.Further studies on the levels of androge receptors mRNA tend to be particularly important.

Analysis on the Infection of HIV/Syphilis among MSM in Zhuhai / 国际检验医学杂志

Objective To learn the awareness rate of HIV/Syphilis knowledge,condom usage,group behaviors and the infections among men who have sex with men (MSM)in Zhuhai and provide scientific foundation for preparing control measures.Methods The internet community was used for calling MSM to join the research.A MSM survey questionnaire was used to collect messages in the place of HIV Voluntary Counseling & Testing(VCT).The blood samples were collected to proceed biological detection.Re-sults Total 247 MSMs were tested,positive rates of HIV,TP specific antibody and non-specific antibody were 8.10% (20/247), 13.36%(33/247)and 10.72% (24/247).The separation between cognition and behavior was common existed in such population. HIV/syphilis infection rates were significant different between MSMs who had multiple sexual partners and those who did not. Conclusion Because the high risk behaviors are commonly existed among MSM in Zhuhai,the prevalence rates of HIV/Syphilis in them are high.It is necessary promote the screening of HIV/Syphilis,enhance the health education of disease control and block the transmission to develop a safe awareness and behaviors in MSM.

Down regulation of miR-33a is involved in gemcitabine chemoresistance in human pancreatic cancer / 中国癌症杂志

Background and purpose:Pancreatic cancer is one of the most deadly human malignant neoplasms. Resistance to chemotherapeutic drugs is a major reason responsible for poor prognosis in the treatment of pancreatic cancer patients. MicroRNA (miRNA, miR) is a family of small non-coding RNA molecules, dysregulated miRNA is associated with various tumor biological function. miR-33a has been widely reported as a metabolism-related miRNA, while its relationship with drug resistance has little understand. This study was focused on the effect of miR-33a on gemcitabine chemoresistance in pancreatic cancer to bring the novel theoretical basis to chemotherapy for pancreatic cancer.Methods:In situ hybridization and Real-time PCR were used to analyze the miR-33a expressions in pancreatic cancer tissue sample and cell lines, respectively. Cell counting kit 8 (CCK-8) assay was used to calculate the IC50 value of different pancreatic cancer cells.Results:miR-33a was down-regulated in pancreatic cancer tissue and cell lines compared with para-cancerous tissues and normal HEK293T cells. Moreover, miR-33a over expression not only could enhance the chemosensitivity to gemcitabine in pancreatic cancer cells, but also rescue the gemcitabine resistance in pancreatic cancer cells.Conclusion:Down regulation of miR-33a in pancreatic cancer decreases the chemosensitivity to gemcitabine, resulting in development of acquired gemcitabine chemoresistance. It provides the theoretical basis to develop a new molecular targeted drug to combine with chemotherapy for pancreatic cancer.

Screening of Pim kinase inhibitors by the establishment of high-throughput ELISA system / 中国癌症杂志

10.3969/j.issn.1007-3969.2013.04.004

Aberrant expression of TCTP protein inhibits cell apoptosis by up-regulating Bcl-xL in human & nbsp;pancreatic cancer / 中国癌症杂志

10.3969/j.issn.1007-3969.2013.05.001

Clinical significance of transcranial Doppler and end-tidal carbon dioxide partial pressure on cerebrovascular reserve capacity in cerebral vessels stenosis patients / 中国医师进修杂志

Objective To study the clinical significance of cerebrovascular reserve (CVR) capacity in cerebral vessels stenosis (CVS) patients with transcranial Doppler (TCD) and end-tidal carbon dioxide partial pressure (PETCO2).Methods Fifty-two CVS patients were divided into two groups:one blood vessel stenosis group (22 cases) and multi blood vessels stenosis group (30 cases).Forty-five normal persons were selected as control group.All the groups were routinely examined with TCD and PETCO2.Hypercapnia was induced by inhaling the carbon dioxide who breathed himself,and hypocapnia was induced by voluntary hyperventilation to investigate the CVR capacity.Results (1)The vasodilator reserve of affected side of one blood vessel stenosis group [(3.16 ± 2.73)％/mm Hg,1 mm Hg =0.133 kPa],the heavier side of multi blood vessels stenosis group [(2.41 ± 1.25)％/mm Hg],and control group [(3.75 ± 1.77)％/mm Hg] had significant difference (F =3.866,P ＜ 0.05).The vasodilator reserve of heavier side of multi blood vessels stenosis group was significantly lower than that of control group (t =-2.657,P ＜ 0.05).The overall reserve of affected side of one blood vessel stenosis group [(3.13 ± 1.38)％/mm Hg],the heavier side of multi blood vessels stenosis group [(2.01 ± 1.89)％/mm Hg],and control group [(3.51 ±0.92)％/mm Hg] had significant difference (F =5.905,P ＜ 0.05).The overall reserve of heavier side of multi blood vesse stenosis group was significantly lower than that of control group and affected side of one blood vessels stenosis group (t =-3.468,2.582,P ＜ 0.05).(2) There was no significant difference among the 3 groups in PETCO2 when eupnea,hypocapnia and hypercapnia.(3) The extent of vascular disease correlated negatively with the vasodilator reserve and overall reserve (r =-0.433 and-0.475,P＜0.05).Conclusions TCD and PETCO2 are simple,economic and effective methods for assessing CVR capacity.The CVR capacity is reduced in patients with cerebral vessels changes.

Synthesis of substrate for angiotensin-converting enzyme and its value in diagnosis of lung cancer / 上海交通大学学报（医学版）

Objective To establish the synthetic method of the substrate for angiotensin-converting enzyme(ACE),and investigate the assay method of sernm ACE. Methods The substrate was prepared by the use of N-hydroxysuccinimide ester in peptide synthesis,and serum ACE was determined by spectrophotometric assay using suhstrate. Results The substrate of furanacryloyl-phenylalanyl-glycyl-glycine with purity of 99.5% was obtained.The K_m value for the substrate was 0.25 mmol/L,the normal reference interval for serum ACE activity was 46.7 U/L to 113.3 U/L,and the within-run and between-run coefficient of variation(CVs)ranged from 3.9 to 4.9%.The serum ACE activity in patients with squamous carcinoma and adenocarcinoma of lung were significantly decreased(P<0.05),while that in patients with lung small cell carcinoma was not significantly decreased(P>0.05). Conclusion The synthesized substrate could be reliably used as a marker for diagnosis of different lung cancers in clinics.

Measurement of the Chinese Humerus / 西安交通大学学报(医学版)

The authors have measured the humerus in 200 pair (115 males and 85females) of the Chinese adults. The results indicate that fhe differencebetween the male and the female humeruses is significant. The maximumlength averages 31. 01 ? 0. 01cm in male and 29. 29 ? 0. 15cm in female. Theaverage length is 30. 50 ? 0. 09cm in male and 28.75 ? 0.14cm in female.The difference in the diameters of the average length of the upper. middle and lower extremities of both sexes is significant. The averagevalue of Shaft index is 77. 23 ? 0. 44 in male and 76. 62 ? 0. 51 in female. Theaverage value of the caliber index is 20. 37 ? 0. 10 in male and 19. 68 ? 0. 12in female. The average value of the head index is 93. 21 ? 0. 18 in male and93. 55 ? 0. 37 in female. The results of the measurement have been comparedwith data published both home and abroad.