Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region / Papillomavirus humano 16 da linhagem D associado a alto risco de câncer de colo do útero em região do nordeste brasileiro

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Comparative Study of Outcome of Treatment of Fracture Shaft of Femur by Open Intramedullary Kuntscher抯 Nail and Closed Intramedullary Interlocking Nail

Fractures of the femoral shaft are one of the most common injuries treated by orthopedic surgeons. These fractures are often associated with polytrauma and can be life-threatening.For physiologically stable individuals, Intramedullary Nailing (IMN) is the most prevalent therapy. Early healing and long-term functional recovery are the goals of fixation. Treatment of modern-day femoral shaft fractures results in excellent outcomes. Aims : To assess the results of intramedullary nailing of femoral shaft fractures by both open and closed methods. Methods : Primary, non-randomized, prospective cohort study, Patients having fracture shaft of femur who was admitted in MGM Medical College & LSK Hospital, Kishanganj was taken for the study, The study period from October 2019 to April 2021. Total 40 cases were enrolled, Open Kuntcher抯 Nail-20 cases & Closed Interlocking Nail-20 cases. Results : Male cases are predominantly high than females among the two groups. Maximum number of fracture (70% in Closed Interlocking Nail group and 80% in Open K-nail group) Radiological union within 15 weeks.Maximum number of the cases found excellent results in both groups. ie, 70% & 65% respectively. In this study, we have not found any poor & fair patients after surgical outcome. Chi-square value 0.1139 & P-value- is 0.735. Conclusion : Except for the period from injury to surgery and operating time, there was no significant difference between the two groups in terms of demographic data, fracture type, and associated co-morbidities and radiological union. When utilised to fix short oblique and transverse fractures near the isthmus of the femur, Kuntscher抯 intramedullary nailing can yield a comparable rate of union to interlocking intramedullary nailing.

Displasia epitelial corneal / Corneal epithelial dysplasia

Las neoplasias intraepiteliales córneo-conjuntival son lesiones premalignas, mal delimitadas, de crecimiento lento y escaso potencial de malignización. Solo el 9 por ciento progresa a carcinoma invasor de células escamosas. Posee varias formas de presentación y tiene múltiples dilataciones vasculares. La displasia epitelial corneal primaria es una forma poco frecuente de neoplasia intraepitelial córnea-epitelial. Se presenta un caso clínico confirmado por estudios anatomopatológicos. En el presente estudio se observó respuesta satisfactoria luego de un mes de tratamiento tópico con 5FU, sin efectos colaterales. El seguimiento durante tres años no ha mostrado signos de recidiva(AU)

Corneal-conjunctival intraepithelial neoplasms are premalignant, poorly demarcated, slow-growing lesions with low malignant potential. Only the 9 percent progresses to invasive squamous cell carcinoma. It appears in several forms and presents multiple vascular dilatations. Primary corneal epithelial dysplasia is a rare form of corneal-epithelial intraepithelial neoplasia. We present a clinical case, confirmed by anatomopathologic studies. In the present study we observed a satisfactory response after one month of topical treatment with 5FU, with no side effects. Follow-up for three years has shown no signs of recurrence(AU)

Study of histopathology reports of loop electrosurgical excision procedure of cervical transformation zone and their correlation with preprocedural cervical biopsy and/or cytology: An audit

Introduction: Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

Cervical Intraepithelial Neoplasia: Analyzing the Disease Present Exclusively in the Endocervical Canal / Neoplasia intraepitelial cervical: Analisando a doença presente exclusivamente no canal endocervical

Abstract Objective To evaluate the role of cervical cytology (Pap smear) in the diagnosis of cervical intraepithelial neoplasia 2 or greater (CIN2+), presented exclusively in the endocervical canal, the clinical-epidemiological characteristics of this lesion, the necessary length of canal to be removed to treat, and the rate of invasive lesion hidden in the endocervical canal. Methods Cross-sectional study, by database analysis, of patients with abnormal cytology (high-grade squamous intraepithelial lesion [HSIL]), without visible colposcopy lesion, submitted to loop electrosurgical procedure (LEEP) to evaluate the association of cytology results with the histological product of the conization, to identify the epidemiological characteristics of endocervical lesion and clinical evolution, using a pvalue< 0.05 and 95% CI. Results In 444 cases, the Pap smear sensitivity for CIN2+ diagnosis was 75% (95% CI: 69.8-79.7), specificity was 40% (95% CI: 30.2-49.5), and the prevalence rate of histological lesion was 73% (95% CI: 70.1-78.7). There was a higher prevalence of CIN2+ in women over 42 years old and invasive cancer in those over 56 years old (p<0.001), and it was necessary to remove 2.6 cm in length of the canal to reduce the chance of recurrence (p<0.006). The rate of invasive cancer was 2.7%. Conclusion Cytology was related to a high prevalence to histological lesion (73%) in the diagnosis of CIN2+ in the endocervical disease; older patients presented a higher relationship with histological lesions in the canal disease, and it was necessary to remove an average of 2.6 cm in length of the endocervical canal to avoid the persistence and progression of CIN. The rate of occult neoplasia in the endocervical canal was 2.7%.

Resumo Objetivo Avaliar o papel da citologia oncótica (CO) no diagnóstico da neoplasia intraepitelial cervical 2 ou maior (NIC2+) presente exclusivamente no canal endocervical, as características clínico-epidemiológicas deste tipo de lesão, o comprimento necessário de canal a ser retirado na conização, e a taxa de lesão invasora oculta no canal endocervical. Métodos Estudo transversal, por análise de base de dados, de pacientes comcitologia alterada, sem lesão colposcópica visível, submetidas a conização por cirurgia de alta frequência (CAF), para avaliar a associação dos resultados citológicos com o produto histológico da conização, as características epidemiológicas da lesão endocervical, e evolução clínica, utilizando o valor de p<0.05 e intervalo de confiança (IC) de 95%. Resultados Nos 444 casos analisados, a sensibilidade da CO para o diagnóstico de NIC 2+ foi de 75% (IC 95%: 69.8-79.7), a especificidade foi de 40% (IC 95%: 30.2-49.5), e a taxa de prevalência de lesão histológica foi de 73% (IC 95%: 70.1-78.7). Houve maior prevalência de NIC2+ em pacientes com mais de 42 anos de idade e de neoplasia invasora naquelas commais de 56 anos (p<0.001), e foi necessário a retirada de 2.6 cm de comprimento de canal para diminuir a taxa de recidiva (p<0.006). Foi identificada uma taxa de 2.7% de neoplasia invasora. Conclusão A citologia esteve relacionada a uma alta prevalência de lesão (73%) no diagnóstico das NIC2+ na doença endocervical; quanto maior a idade, maior foi a relação da histologia com a citologia de canal, e se fez necessário retirar uma média de 2.6 cmde comprimento de canal para evitar a persistência e a progressão da NIC. A taxa de neoplasia oculta no canal endocervical foi 2.7%.

Progression of cervical intraepithelial neoplasia grade 2 lesions among Japanese women harboring different genotype categories of high-risk human papillomaviruses / Journal of Rural Medicine

Background: This study aimed to examine whether genotype categories of high-risk human papillomaviruses (HR-HPVs), when divided into HPV16/18, HPV 31/33/45/52/58, and HPV35/39/51/56/59/68, had an effect on the time required for and the proportion of cases that progressed to cervical intraepithelial neoplasia (CIN) grade 3 among women with CIN2.Patients: A total of 160 women aged 20–49 years and having CIN2 were recruited between January 2008 and June 2018. The time required for progression to CIN3 was determined by Kaplan-Meier time-to-event analysis. HPV genotypes were determined using the Linear Array HPV genotyping test.Results: During an average follow-up time of 22 months, 62 (39%) women with CIN2 progressed to CIN3, whereas 34 (21%) eliminated HR-HPVs and became cytologically normal. The majority (63%) of the women harboring HPV16/18 progressed to CIN3 with a 50% progression time of 11 months, whereas 26% of those harboring HPV31/33/45/52/58 progressed to CIN3 with a 50% progression time of 70 months.Conclusion: For every patient diagnosed with CIN2, genotyping to distinguish HPV16/18 from other HR-HPVs should be performed. Therefore, electing a surgical treatment, such as conization, should be considered as the primary option for women who are positive for HPV16/18, particularly when they are likely to be lost for follow-up or are 40 years old or older. In contrast, follow-up cytology should be repeated every 12 months for women harboring non-16/18 HR-HPVs. Those who tested negative for HR-HPV may be followed at the maximum interval of 24 months.

Overexpression of LncRNA SLC25A25-AS1 Inhibits Proliferation‚ Migration‚ and Invasion of HeLa Cells / 中国生物化学与分子生物学报

Long non-coding RNA SLC25A25-AS1 has a tumor inhibition effect in the development of colorectal cancer. However‚ the mechanism of SLC25A25-AS1 in cervical cancer needs further study. We studied the abnormal expression of SLC25A25-AS1 in the serum of the patients with cervical cancer and the patients with cervical intraepithelial neoplasia (CIN) and explored the mechanism of SLC25A25-AS1 in the development of cervical cancer. The expression levels of SLC25A25-AS1 in the serum of normal controls‚ patients with cervical cancer‚ and patients with CIN were detected by RT-qPCR. The important role of SLC25A25-AS1 in HeLa cells was analyzed in vitro and in vivo experiments. Compared with the normal group‚ the expression level of serum SLC25A25-AS1 was decreased in patients with cervical cancer. In vitro‚ overexpression of SLC25A25-AS1 inhibited cell proliferation‚ migration‚ and invasion of HeLa cells. Tumor formation in nude mice assay showed that the subcutaneous tumor weight and volume of nude mice injected with SLC25A25-AS1-overexpressed HeLa cells were significantly smaller than that of nude mice injected with control cells (P<0. 05). SLC25A25-AS1 may play an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Prospective comparative study between colposcopy and histopathology for diagnosis of CIN and carcinoma cervix

Background: Cervical cancer develops from precursor lesions and detection of these lesions is of utmost importance. The detection of precancerous lesions is made with help of screening tests most important include PAP smear and colposcopy. So we conducted this study to understand the role of colposcopy in down staging of Carcinoma cervix.Methods: We performed a prospective study between Jan 2018 to Dec 2018 on 180 subjects chosen from patients who sought consultation for various gynaecological complaints between age group of 18-60 years. A Pap smear followed by a colposcopy was performed and colposcopic directed biopsies were taken and subjected to histolopathological examination.Results: Colposcopy had a sensitivity of 83.3%, specificity of 78.5%, PPV of 68.9% for CIN 1. It had a sensitivity of 90.9%, specificity of 95.2%, PPV of 83.33% for CIN 2 and 3 when co related with gold standard histopathology which is much higher as compared to Pap smear.Conclusions: Colposcopy is an effective tool in down staging of Carcinoma cervix.

Comparative study of causative organism in erosive cervicitis, cervical intra epithelial neoplasia and carcinoma cervix using Pap smear

Background: Cervical cancer is the third largest cause of cancer mortality in India after cancers of the mouth and oropharynx, and oesophagus, accounting for nearly 10% of all cancer related deaths in the country.Methods: The present study carried out 300 patients in Gajra Raja Medical College in the Department of Obstetrics and Gynaecology, OPD and indoor admitted patients from July 2016 to December. 2016. The selected patients were examined with care to note any cervical lesion, appearance of cervix, nature of any cervical/ vaginal discharge. Then a cervical scrape was taken with an Ayre’s spatula and slide stained and then examined.Results: The maximum cases of HPV were seen in CIN, LSIL and HSIL. Maximum incidence of all cases was seen in the age group of 30-50 yrs. The women married before 18 years had the highest incidence of CIN and HPV infection. Majority of the cases of cervicitis were co-infected with H-Vaginalis and Trichomonas. Most women opted for a sterilization procedure rather than any other method of contraception. Use of no contraception puts these women at a high risk of acquiring HPV infection from infected partners.Conclusions: Occurrence of HPV infection declines with increasing grades. Most of the patients with HPV infection had presented with non-specific symptoms of discharge P/V or lower abdominal pain.

Prevalence and Management of CIN by Colposcopy among VIA Positive Cases in a Tertiary Level Hospital of Bangladesh

Background: Cervical cancer is the second most commoncancer among women in Bangladesh where CIN is theforerunner. Visual inspection of cervix with acetic acid (VIA) isadopted as national cervical cancer screening programme inBangladesh. All positive VIA cases are evaluated bycolposcopy.Objective: This population-based study was conducted inFaridpur Medical College Hospital for 6 years (2013 - 2018) toevaluate the prevalence of CIN among the VIA positive casesand performance of the clinic for colposcopic management ofCIN.Materials and Methods: A total of 2102 VIA positive caseswere evaluated by colposcopy during the study period.International Federation of Cervical Pathology and Colposcopy(IFCPC) 2011 nomenclature was used for colposcopicdiagnosis. Diagnosed CIN were treated accordingly.Results: During the study period, 548 (26.1%) cases werecolposcopically diagnosed as CIN. Among them, 370 (65.5%)were low grade squamous intraepithelial lesion (CIN-I) and 178(32.5%) were high grade squamous intraepithelial lesion (CINII and III). Colposcopicaly diagnosed 237 (64.1%) of low gradesquamous intraepithelial lesion (LSIL) and 132 (74.2 %) of highgrade squamous intraepithelial lesion (HSIL) casesreceived treatment and histopathological confirmation.Treatment produces were used like thermocoagulation, LoopElectrosurgical Excision Procedure (LEEP), biopsy,hysterectomy and post treatment follow up.Conclusion: From this study, we got information about thedemography and prevalence of CIN among VIA positive casesat the same time management of CIN to prevent invasivecervical cancer. We adopted ‘See and treat’ protocol formanagement, which is well accepted, feasible and useful inBangladesh.

1. The Advance of Utilizing Real World Data Under Pharmaceutical Regulatory Schemes Regarding the Approval Review and Post-marketing Safety Assessment / 薬剤疫学

Pharmaceutical regulatory schemes concerned with real world data have been changing remarkably in terms of both drug development and post-marketing.As for drug development, ICH proposed “GCP Renovation” , which includes modernization of E8 Guideline (General Consideration for Clinical Trials) and subsequent renovation of E6 Guideline (Good Clinical Practice). It covers pragmatic clinical trials, randomized controlled trials using patient registry data, and even observational studies using real world data. In the US, “The 21st Century Cures Act” refers to the proposal concerning speeding up the approval review by making clinical trials more efficient. In fact, there are some cases where real world data was used in the approval review of expanding the application. Also, in Japan, Clinical Innovation Network (CIN) plan was announced, and utilizing the natural history data like patient registry as the control group of clinical trials for the approval review is now under consideration.As regards post-marketing surveillance, “Conditional & Accelerated Approval” (October 20, 2017, Yakuseiyakushinhatsu 1020 No. 1) stated that post-marketing confirmation of validity of efficacy and safety using real world data, such as Medical Information Database Network (MID-NET) project and patients registries in CIN plan, is required to get the early approval. Moreover, “The Ordinance on Good Post-Marketing Practice” (October 26, 2017, MHLW Ordinance No. 116) newly provided “Post-marketing Database Study” , which is conducted by use of medical information database like MID-NET, and utilizing real world data for post-marketing safety monitoring began.

Prevention of contrast-induced nephropathy by Cordyceps among patients undergoing percutaneous coronary procedures using intravenous contrast

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> This study aimed to determine the efficacy and safety of Cordyceps in preventing occurrence of contrast-induced nephropathy (CIN) among patients undergoing CA / PCI using IV contrast compared to standard therapy.</p><p style="text-align: justify;"><strong>METHODS:</strong> We searched Medline, Embase, Cochrane database, and Google Scholars for RCTs involving the use of Cordyceps in contrast-induced nephropathy. We used the search keywords "Cordyceps" and "contrast-induced nephropathy" with the Boolean operator "AND" and filtering search results to include only randomized controlled trials and clinical trials. Three trials were found which satisfied all the inclusion criteria and none of the exclusion criteria.</p><p style="text-align: justify;"><strong>RESULTS:</strong> No patient developed clinical renal failure, adverse reactions, or side effects with the Cordyceps arm. CIN occurred in 26 out of 285 patients. The incidence of CIN was less in the Cordyceps group compared to the standard therapy group (p < 0.05, CI 0.20, 1.00).</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Cordyceps shows a trend towards prevention of CIN and a decrease in biomarkers for acute kidney injury. More studies with larger populations need to be performed to further clarify its preventive effects.</p>

Expressions of HPV16/18 E6 protein and its clinical, predictive value of cervical intraepithelial neoplasia / 上海交通大学学报（医学版）

Objective: To investigate the clinical significance and predictive value of human papillomavirus (HPV) 16/18 E6 protein in the different cervical intraepithelial neoplasia. Methods: The expression of HPV16/18 E6 in 10 normal cervical tissues, 33 cervical intraepithelial neoplasia I (CIN I ), 31 CIN II-III, 30 cervical cancers was detected by immunohistochemistry, explored the expression difference and the relationship with the clinicopathological characteristics of cervical cancer and the prognosis of different CIN. Results: The positive expression rates of HPV16/18 E6 in normal cervical tissues, CIN I, CIN II-III and cervical cancer group were up-regulated (χ2=19.82, P=0.000). HPV16/18 E6 increased positive expression rates in the low grade and the big size tumors of cervical cancer tissues were detected (P=0.033, P=0.011). There were positive correlations between the overexpression and the pathological grade, tumor size, poor prognosis of cervical cancers respectively (r=0.456, P=0.011; r=0.578, P=0.000; r=0.645, P=0.000). The sensitivity, specificity, and diagnostic accuracy rates of HPV16/18 E6 positive expression to the progression of CIN I, CIN II-III and cervical cancer were respectively 100.00%, 62.50%, 43.75%; 96.77%, 91.30%, 92.86%; 96.97%, 83.87%, 66.67%. Conclusion: HPV16/18 E6 overexpression plays an important role in the generation, development and the poor prognosis of cervical cancer. HPV16/18 E6 has a good predictive value for the prognosis and hierarchical management of cervical diseases.

Influence of 131 I therapy on thyroid function and bone metabolism in patients with Graves disease / 中国基层医药

Objective To analyze the influence of 131 I therapy on thyroid function and bone metabolism in patients with Graves 's disease. Methods From February 2014 to January 2017,60 Graves patients in Shaoxing Central Hospital were studied. According to the random number table method,they were divided into observation group and control group,with 30cases in each group. The patients in the control group were treated with methimidazole,and the patients in the observation group were treated with 131 I combined with methimidazole. After treatment for 1 month, the clinical efficacy,three triiodothyronine (FT3 ),free thyroxine (FT4 ),thyroid stimulating hormone (TSH) concen-tration,parathyroid hormone (PTH),procollagen amino terminal propeptide (PINP) and osteocalcin (OCN),1,25 hydroxyvitamin D3(1,25(OH)2D3),bone mineral density (BMD),the incidence of goiter,exophthalmos,incidence of hypothyroidism of the two groups were observed. Results After treatment,the total effective rate of the observation group was 93. 33％ ,which of the control group was 73. 33％ . There was statistically significant difference between the two groups (χ2 = 4. 320,P = 0. 037). Before treatment,the levels of FT3 ,FT4 ,TSH between the two groups had no statisticallysignificant differences (all P > 0. 05). After treatment,the FT3 ,FT4 levels of the observation group were (12. 41 ± 1. 24) pmol/ L,(18. 33 ± 4. 25) pmol/ L,respectively,which were significantly lower than those of the control group[ (15. 98 ± 1. 30)pmol/ L,(22. 75 ± 4. 31)pmol/ L](t = 10. 884,P < 0. 0001;t = 4. 000,P < 0. 000). The concentration of TSH in the observation group was (2. 16 ± 0. 39)mIU/ L,which was significantly higher than that of the control group[(1. 72 ± 0. 34)mIU/ L](t = 4. 658,P < 0. 0001). Before treatment,the PTH,PINP,OCN,1,25 (OH)2D3 and BMD between the two groups had no statistically significant differences (all P > 0. 05). After treat-ment,the PINP and OCN of the observation group were (43. 21 ± 3. 69) μg/ L,(27. 42 ± 6. 48) μg/ Lrespectively, which were significantly lower than those of the control group [(55. 87 ± 3. 71) μg/ L,(31. 84 ± 6. 55) μg/ L] (t =13. 252,P < 0. 0001;t = 2. 628,P = 0. 011). The PTH,1,25 ( OH)2D3 and BMD of the observation group were (55. 87 ± 3. 18)ng/ L,(25. 16 ± 2. 84) nmol/ L,(0. 98 ± 0. 17) g/ cm2 ,respectively,which were significantly higher than those in the control group [(49. 89 ± 3. 21)ng/ L,(23. 2 ± 2. 76)nmol/ L,(0. 85 ± 0. 15)g/ cm2 ] (t = 7. 249, P < 0. 001;t = 2. 697,P = 0. 009;t = 3. 141,P = 0. 003). After treatment,the incidence rate of exophthalmos in the observation group was 6. 67％ ,which in the control group was 30. 00％ ,there was statistically significant difference between the two groups (χ2 = 5. 455,P = 0. 020). The incidence rate of goiter of observation group was 3. 33％ ,which was significantly lower than 23. 33％ of the control group (χ2 = 5. 192,P = 0. 023). The incidence rate of hypothy-roidism of the observation group was 13. 33％ ,which in the control group was 10. 00％ ,the difference between the two groups was not statistically significant (χ2 = 0. 162,P = 0. 688). Conclusion 131 I therapy has good clinical effect on Graves disease. It can effectively improve the thyroid function and bone metabolism and has high safety. It is worthy of widely application and popularizing in clinic.

Expressions of HPV16/18 E6 protein and its clinical, predictive value of cervical intraepithelial neoplasia / 上海交通大学学报（医学版）

Objective·To investigate the clinical significance and predictive value of human papillomavirus (HPV) 16/18 E6 protein in the different cervical intraepithelial neoplasia. Methods·The expression of HPV16/18 E6 in 10 normal cervical tissues, 33 cervical intraepithelial neoplasiaⅠ (CINⅠ ), 31 CINⅡ- Ⅲ, 30 cervical cancers was detected by immunohistochemistry, explored the expression difference and the relationship with the clinicopathological characteristics of cervical cancer and the prognosis of different CIN. Results·The positive expression rates of HPV16/18 E6 in normal cervical tissues, CINⅠ , CINⅡ - Ⅲ and cervical cancer group were up-regulated (χ2=19.82, P=0.000). HPV16/18 E6 increased positive expression rates in the low grade and the big size tumors of cervical cancer tissues were detected (P=0.033, P=0.011). There were positive correlations between the overexpression and the pathological grade, tumor size, poor prognosis of cervical cancers respectively (r=0.456, P=0.011; r=0.578, P=0.000; r=0.645, P=0.000).The sensitivity,specificity,and diagnostic accuracy rates of HPV16/18 E6 positive expression to the progression of CINⅠ,CINⅡ-Ⅲand cervical cancer were respectively 100.00%, 62.50%, 43.75%; 96.77%, 91.30%, 92.86%; 96.97%, 83.87%, 66.67%. Conclusion·HPV16/18 E6 overexpression plays an important role in the generation, development and the poor prognosis of cervical cancer. HPV16/18 E6 has a good predictive value for the prognosis and hierarchical management of cervical diseases.

Analysis of the value of HPV E6/E7 mRNA detection in screening lesions at grade CIN 2 and above / 国际检验医学杂志

Objective To explore the clinical value of HPV E6/E7 mRNA in screening lesions at grade CIN2 and above.Methods A total of 120 cases with CIN and suspected cervical cancer treated in our hospital from January 2014 to September 2016 were selected.According to the results of pathological examination,60 patients with CIN2,CIN3 and invasive cancer were selected as the research group.60 patients with normal CIN1 and CIN1 were selected as control group.The results of TCT,HPV DNA and HPV E6/E7 mRNA were detected and analyzed.Results In 120 patients,the total positive rate of TCT was 55%,the total positive rate of HPV DNA was 87.5%,the total positive rate of HPV E6/E7 mRNA 60.8% HPV E6/E7;control group mRNA positive rate of 78.3% was significantly higher than the positive rate of HPV DNA 36.7%(P<0.05),HPV in the study group were E6/E7 mRNA positive rate of 85.0% was significantly lower than the positive rate of HPV DNA(96.7%);HPV E6/E7 mRNA CIN1,quantitative CIN2,CIN3 and invasive carci-noma were(4 867.31 ± 694.84),(8 943.51 ± 986.23),(28 243.10 ± 10 963.21),(3 610.84 ± 412.64)copies/mL;HPV E6/E7 mRNA quantitative CIN3 values were significantly higher than that of CIN 2,CIN1 and infil-tration of cancer and the control group(P<0.05),E6/E7 mRNA CIN2 quantitative HPV the value of CIN1 was significantly higher than that of control group(P< 0.05).Two methods of detecting HPV DNA and HPV E6/E7 mRNA in the screening of CIN2 and above lesions,the sensitivity of 84.5% DNA 93.8% HPV sensitivity was higher than that of HPV E6/E7 mRNA(P<0.05)HPV E6/E7 21.6%;specificity the speci-ficity of mRNA was 53.6% higher than that of HPV DNA(P<0.05),HPV DNA.HPV ROC curve E6/E7 mRNA were 0.581 and 0.681,the difference was statistically significant(P<0.05).Conclusion The specific-ity and accuracy of HPV,E6/E7 and mRNA in detecting cervical lesions over CIN2 and above are higher than those of HPV and DNA.It is of certain diagnostic value for screening cervical lesions over CIN 2 and above.

Selection of DNA aptamers to cervical intraepithelial neoplasia by SELEX / 生物工程学报

An in vitro synthesized random ssDNA library was subjected to 12 rounds of selection against anti-screening cells and sieving cells by SELEX. Normal and inflammatory cervical exfoliation cells were selected as anti-screening cells, and the cervical exfoliation cells of low-grade squamous intraepithelial lesion (CIN1), high-grade squamous intraepithelial lesion (CIN2, CIN3) and cervical carcinoma were selected as sieving cells during the screening process. Then, the highly specific aptamer CIN-Ap4 was established by the analysis of the specificity, affinity and cell immunofluorescence, which can be used as biomarker for Cervical Intraepithelial Neoplasia. Prime Premier 5.0 was applied to design a random ssDNA library. According to the fixed sequence at both ends of the library, a pair of primers were designed and synthesized. At the same time, the optimal annealing temperature, cycle times and primer concentration ratio of PCR procedure were selected. The results under the optimal condition are shown as follows. In the 50 μL reaction system, the optimum reaction conditions of symmetry PCR are as follows: annealing temperature is 49.5 ℃, number of cycles is 15. The optimal reaction conditions of indirect asymmetric PCR are as follows: the primer concentration ratio is 80:1, and the number of cycles is 35. The experiment proves that the oligonucleotide library is constructed successfully, and the highly specific dsDNA and ssDNA can be obtained under optimal PCR conditions with good repeatability, which establishes the foundation for the further exploration and experimentation.

Progress of prokineticin 2 in cardiovascular diseases / 中国药理学通报

Cardiovascular diseases are characterized by cardiac and vascular dysfunction. Prokineticin 2 ( PK2 ) is a newly found secretory peptide which plays a key role in the physiology homeostasis via prokineticin receptor 1 and 2 ( PKR1 and 2). Furthermore, PK2/PKR1 signaling pathway plays an important role in protecting cardiovascular diseases. Here we discuss the effect of PK2/PKR1 signaling in myocardial infarction, conges-tive heart failure and vascular endothelial dysfunction.

Controversia en el tratamiento de la lesión intraepitelial escamosa de alto grado (NIC II) / Controversy in the treatment of high-grade squamous intraepithelial lesion (CIN II)

Contexto: el cono LLETZ actualmente es el tratamiento de las NIC de alto grado. La resistencia al procedimiento es argumentada por los efectos del sobretratamiento (estenosis e insuficiencia cervical), sobre todo cuando se utilizan métodos ablativos destructivos en lugar de la resección quirúrgica ambulatoria (LLETZ). Objetivo: analizar el diagnóstico y tratamiento del NIC II mediante cono y legrado en pacientes que acuden al servicio de Patología del tracto genital inferior del Hospital Oncológico SOLCA-Quito Ecuador. Sujetos y métodos: en este estudio epidemiológico descriptivo observacional de corte transversal se analizaron expediente clínicos de 820 pacientes con diagnóstico histopatológico por biopsia de NIC II; mujeres entre 17 a 82 años que acudieron al servicio de patología del tracto genital inferior sujetas a control, en estas pacientes se realizó 530 legrados. El estudio fue realizado en el Hospital Oncológico SOLCA de Quito Ecuador, de los años 2004 a 2013. Resultados: la histopatología de los conos libres de neoplasia representa el 98,66% (n=809); existen 11 casos de neoplasias residuales (1,34%). El 53,7% de casos presenta una lesión igual o mayor que en biopsia, lo que justifica el cono. Conclusión: el procedimiento de cono LLETZ tiene gran utilidad diagnóstica, terapéutica y pronóstica en mujeres que presentan NIC II y otras patologías similares. (AU)

Background: the LLETZ cone is currently the treatment of high grade NICs. The resistance to the procedure is argued by the effects of overtreatment (stenosis and cervical insufficiency), especially when destructive ablative methods are used instead of ambulatory surgical resection (LLETZ). Objective: to analyze the diagnosis and treatment of CIN II by means of cone and curettage in patients attending the pathology department of the lower genital tract of the SOLCA-Quito Ecuador Oncology Hospital. Subjects and methods: in this cross-sectional descriptive epidemiological observational study, we analyzed clinical records of 820 patients with histopathological diagnosis by CIN II biopsy; women between 17 and 82 years old who visited the pathology service of the lower genital tract subject to control, in these patients 530 catheters were performed. The study was conducted at the SOLCA Oncology Hospital of Quito, Ecuador, from 2004 to 2013. Results: the histopathology of neoplasm-free cones represents 98.66% (n = 809); there are 11 cases of residual neoplasms (1.34%). 53.7% of cases present a lesion equal to or greater than in biopsy, which justifies the cone.(AU)