Objective To investigate the efficacy of bevacizumab combined with paclitaxel and platinum-based chemotherapy in advanced metastatic cervical cancer and its effect on T lymphocyte subsets and tumor markers. Methods Sixty patients with advanced metastatic cervical cancer (treated in our hospital) were randomly divided into control (30 cases) and treatment (30 cases) groups. All patients were given radiotherapy; the control group received paclitaxel and platinum-based chemotherapy, whereas the treatment group received the same with added bevacizumab. The pain conditions (visual analog score (VAS)) and quality of life (Karl Fischer quality of life (KPS)), clinical efficacy, T lymphocyte subset levels (CD3+, CD4+, and CD8+), tumor markers (carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), and squamous epithelial carcinoma-associated antigen (SCCA)) and adverse reactions were compared between the two groups. Results The VAS score, serum CA125, CEA, SCCA, and CD8+ level were significantly reduced in both groups after treatment (P < 0.05), and it significantly decreased in the treatment group compared with the control group (P < 0.05). KPS score, CD3+, and CD4+ levels significantly increased after treatment in the two groups (P < 0.05), and compared with the control group, the treatment group significantly increased (P < 0.05). Moreover, the total effective rate (66.67%) was significantly higher than that in the control group (40.00%) (P < 0.05), and no significant difference existed in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Bevacizumab combined with paclitaxel and platinum-based chemotherapy can effectively reduce the pain and improve the immune function and quality of life of patients with advanced metastatic cervical cancer. This chemotherapy is also safe and effective.

Objective:To analyze the risk factors of postoperative bleeding after CT-guided percutaneous fly biopsy, and to construct a nomogram model for predicting postoperative bleeding.Methods:A total of 328 patients with CT-guided percutaneous fly biopsy who were admitted to the Affiliated Hospital of Ningbo University School of Medicine from June 2019 to March 2021 were selected, and the general clinical data of the patients were retrospectively analyzed. The patients were divided into observation group and control group according to postoperative bleeding. Statistical analysis was performed on clinical data of patients with statistical significance, receiver operating characteristic (ROC) curve analysis on continuous variables with statistical significance, and Logistic multiple regression analysis on all variables with statistical significance. The risk factors of bleeding complications in CT-guided percutaneous lung biopsy were obtained, and a Nomogram model for predicting bleeding after percutaneous lung biopsy was constructed using the R language software 4.0 "rms" package.Results:The results of the study showed that the size of the mass , the depth of the mass, the number of punctures, the number of cases with inflammation around the lesion , and the number of cases with chronic lung lesions in the observation group were greater than those in the control group: (5.20 ± 1.20) cm vs. (4.30 ± 0.90) cm, (4.30 ± 0.60) cm vs. (2.90 ± 0.30) cm, (2.70 ± 0.60) times vs. (2.30 ± 0.50) times, 38(14, 70) cases vs. 17(24, 60) cases, 102(39, 40) cases vs. 41(59, 40) cases; while the number of normal preoperative prothrombin time (PT) in the observation group was less than that in the control group: 4(5, 80) cases vs. 151(58, 30) cases ( P<0.05). ROC curve analysis was performed on the continuous variables with statistical significance in the control table of patients′general clinical data. The results showed that the area under the curve for swelling size, swelling depth, number of punctures, and number of tissue blocks cut were 0.563, 0.714, 0.680, and 0.559, respectively; the optimal cut-off values were 53.00 cm, 5.56 cm, 2.00 times, and 1.00 blocks ( P<0.05). The univariate indicators were included in the Logistic multiple regression model, and the results showed that tumor depth, puncture times, inflammation around the lesion, and abnormal preoperative PT were the risk factors for complications of percutaneous lung biopsy under CT ( P<0.05). The internal validation results showed that the Nomogram model predicted the risk of bleeding complicated by percutaneous lung biopsy under CT, with a C index of 0.687 (95% CI 0.241 - 1.988). The calibration curve showed good agreement between the observed and predicted values. The Nomogram model predicted percutaneous lung biopsy under CT with a bleeding risk threshold of >0.16, and the Nomogram model provided a clinical net benefit; in addition, the Nomogram model had a higher clinical net benefit than independent indicators. Conclusions:In conclusion, patients with poor coagulation function, inflammation around tumor lesions, deeper lesions, and more puncture times are more prone to bleeding. The Nomogram model constructed in this study has a high clinical application value for predicting the bleeding complications of CT-guided percutaneous lung biopsy.

Objective:To explore potential role and mechanism of N6-methyladenine(m6A)RNA methylation regulators in prognosis and tumor immune microenvironment of cervical cancer.Methods:Clinical and survival data as well as RNA sequencing data were acquired from TCGA and GEO database.Expressions and correlation among m6A RNA methylation regulators were analyzed by bioinformatics analysis and tissue validation experiments.LASSO Cox regression analysis was used to generate a prognostic risk sig-nature based on m6A regulators.Two m6A-modification patterns were identified based on m6A regulators and their abundance of im-mune cell inflitration were analyzed by ssGSEA.Results:Compared with normal tissues,RBM15,IGF2BP2,IGF2BP3,FMR1,YTHDF1,METTL3 and YTHDF2 expressions were significantly up-regulated in cervical cancer tissues,while ZC3H13,METTL4,YTHDC1,FTO and ALKBH3 expressions were significantly down-regulated.Five m6A regulators HNRNPC,LRPPRC,METTL3,ELAVL1 and FMR1 were selected to establish prognostic risk signature,whose expressions in cervical cancer were verified by HPA database and qRT-PCR with good predictive value,and could be used as independent poor prognostic factor(AUC=0.734).Based on expressions of 25 m6A regulators,two m6A modification patterns m6Acluster A and m6Acluster B were determined.There were differ-ences between two groups in biological functions,signal pathways and immune cells infiltration levels in tumor microenvironment.Conclusion:m6A RNA methylation regulators are closely related to prognosis and immune infiltration of cervical cancer,which provides guidance for immunotherapy strategy.

OBJECTIVE: To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. METHODS: Whole exome sequencing was carried out for the proband from the pedigree. Suspected FH gene variants were validated by Sanger sequencing. Clinical manifestation and histopathological examination were used to analyze the pedigree comprehensively. RESULTS: The pedigree met the clinical diagnostic criteria for HLRCC syndrome. The whole exome sequencing showed that the FH gene of the proband had a heterozygous missense variant of c.1490T>C (p.F497S), which was consistent with the Sanger sequencing. The mother, daughter and son of the proband all had the heterozygous missense variant of c.1490T>C (p.F497S). According to the American Society of Medical Genetics and Genomics Classification Standards and Guidelines for Genetic Variations, c.1490T>C (p.F497S) (PM2+PP1-M+PP3+PP4) was a possible pathogenic variant. Based on our literature search, this variant was a new variant that had not been reported. CONCLUSION The FH gene missense variant of c.1490T>C (p.F497S) may be the cause of the HLRCC syndrome pedigree, which provides a basis for the genetic diagnosis and genetic counseling of the HLRCC syndrome.
Carcinoma, Renal Cell/genetics* ; Humans ; Kidney Neoplasms/genetics* ; Leiomyomatosis/pathology* ; Mutation ; Neoplastic Syndromes, Hereditary ; Pedigree ; Phenotype ; Skin Neoplasms ; Uterine Neoplasms

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Objective To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient′s stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results (1) The total number of hospitalized patients with stageⅠa2 toⅡa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01). The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557), respectively; χ2=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stageⅠ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions The trend in proportion among hospitalized patients for stageⅠa2 toⅡa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion>1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ²=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Objective To investigate the safety and clinical effect of laparoscopic radical parametrectomy in the treatment of unexpected cervical cancer . Methods A retrospective analysis was made on clinical characteristics of 15 patients who were diagnosed as unexpected cervical cancer from January 2008 to December 2014.The age of the patients was between 29 and 67 years old, with an average of 43.9 years old.The indications for hysterectomy were cervical intraepithelial neoplasia (CIN) grade 2-3 in 7 cases, uterine myoma in 3 cases, dysfunctional uterine bleeding in 2 cases, uterine prolapse in 2 cases and adenomyosis in 1 case. Pathological results after the hysterectomy included 13 cases of cervical squamous carcinoma and 2 cases of adenocarcinoma .The lesions were all confined to the cervix , with 4 cases of stage ⅠA2 disease and 11 cases of stage ⅠB1 .The lymph-vascular space invasion was found in 4 cases.The operation interval between the two operations was 3-7 d (mean, 4.6 d).They were all given laparoscopic radical parametrectomy . Results The operation time was 212-285 min (mean, 249.6 min), and the blood loss was 250-500 ml ( mean, 376 ml) .Postoperative pathological findings showed no residual disease .Only one patient had left pelvic lymph node mestastasis .Two patients had intraoperative complications , including 1 bladder injury and 1 ureteral injury .There were 3 cases of postoperative complications , including 2 cases of uroschesis and 1 case of lymphocyst .The follow-up time was 6-84 months ( median, 48 months).No recurrence was seen.The 1-, 3-, 5-year survival rates were 100%, 93.3%, 86.7%, respectively. Conclusions Laparoscopic radical parametrectomy in the treatment of unexpected cervical cancer is difficult to perform and has more complications . This surgical method is applicable to those who refused postoperation radiotherapy or required retaining ovarian function .

Objective To investigate the effect of phosphoinositide-3-kinase inhibitor LY294002 on the differentiation of human embryonic stem cells (HESC) into more mature insulin-producing cells. Methods HESCs were induced to differentiate into insulin-producing cells through five stages. Nicotinamide and B27 (group B27), nicotinamide and LY294002 (group LY) were used to induce the nesting positive cells into mature insulin-producing cells. The morphological change of each stage was observed under microscope , and expressions of insulin, c-peptide, somatostatin and glucagon were identified by immunofluorescence staining. Results After 14 days in stage 5 , there was no significant difference in rate of insulin positive cells between group LY and group B27 (P﹥0.05), but rates of somatostatin and glucagon positive cells in group LY were lower than those in group B27(P﹤0.05). Furthermore, the co-stained rate of somatostatin and insulin in group LY was also lower than that in group B27 (P﹤0.05). Conclusion HESCs can be induced to differentiate into more mature insulin-producing cells by phosphoinositide-3-kinase inhibitor LY294002 in serum-free culture medium.

Objective To discuss the feasibility and the effects of percutaneous vertebroplasty (PVP) in the treatment of the osteoporotic compression fracture in theupper and middle thoracic vertebrae.Methods The study included 101 patients.55 cases were treated with PVP (observation group) and 46 cases were treated with conservative treatment (control group).The clinical efficacy of those two different treatment methods was evaluated by the changes of VAS score,ODI score,vertebral height and Cobb angle before versus after treatment.Results VAS and ODI scores at 48 hours and 6 weeks after treatment was significantly lower in observation group than in the control group (all P＜0.05).Although there was no significant difference in VAS and ODI scores between the two groups after 6 months of treatment (both P＞0.05),the anterior and middle vertebral height was decreased and Cobb angle of spine was increased in control group as compared with observation group (both P＜ 0.05).Conclusions PVP is an effective and safe method in the treatment of osteoporotic vertebral compression fractures in upper and middle thoracic vertebrae.The short-and long-term evaluation indexes are better in PVP than in conservative treatment.But the surgery should be proceeded under highly clear perspective equipment by the surgeons with highly level professional technology.Because the surgery is highly risky,surgery should be proceeded with cautions.