Metabolomics and transcriptomics strategies to reveal the mechanism of diversity of maize kernel color and quality.

BACKGROUND: Maize has many kernel colors, from white to dark black. However, research on the color and nutritional quality of the different varieties is limited. The color of the maize grain is an important characteristic. Colored maize is rich in nutrients, which have received attention for their role in diet-related chronic diseases and have different degrees of anti-stress protection for animal and human health. METHODS: A comprehensive metabolome (LC-MS/MS) and transcriptome analysis was performed in this study to compare different colored maize varieties from the perspective of multiple recombination in order to study the nutritional value of maize with different colors and the molecular mechanism of color formation. RESULTS: Maize kernels with diverse colors contain different types of health-promoting compounds, highlighting that different maize varieties can be used as functional foods according to human needs. Among them, red-purple and purple-black maize contain more flavonoids than white and yellow kernels. Purple-black kernels have a high content of amino acids and nucleotides, while red-purple kernels significantly accumulate sugar alcohols and lipids. CONCLUSION: Our study can provide insights for improving people's diets and provide a theoretical basis for the study of food structure for chronic diseases.

The Urodynamics and Survival Outcomes of Different Methods of Dissecting the Inferior Hypogastric Plexus in Laparoscopic Nerve-Sparing Radical Hysterectomy of Type C: A Randomized Controlled Study.

BACKGROUND: Little data exist about the impact of dissection methods on bladder function during nerve-sparing radical hysterectomy (NSRH). This randomized controlled trial compared the urodynamic and survival outcomes of different methods dissecting the inferior hypogastric plexus (IHP) during laparoscopic NSRH. METHODS: Eligible patients presenting with stage IB cervical cancer from 9 May 2013 to 27 October 2015 were randomized at a ratio of 1:1 and subjected to waterjet (study group) or traditional blunt (control group) dissection of the IHP for laparoscopic type C radical hysterectomy. Participants were subjected to urodynamic evaluations before and after NSRH. The primary measurement was the proportion of patients with residual urine (RU) ≤ 100 ml, while secondary measurements included urodynamic parameters, disease-free survival (DFS), and overall survival (OS). RESULTS: In total, 191 women met the inclusion criteria, and 160 patients were included in the final analysis, with 80 randomized to each group. At 14 days after NSRH, the study group had more patients with RU ≤ 100 ml than the control group (82.5% vs. 62.5%, p = 0.005). The study group had similar urodynamic outcomes of preoperative and postoperative tests. Comparison with the study group and preoperative tests revealed the control group had significant bladder function impairment at 4 months after NSRH. After a median follow-up of 33 months, the dissection methods had no significant impact on DFS or OS. CONCLUSIONS: Waterjet dissection of the IHP in laparoscopic NSRH resulted in a more rapid return of normal urodynamics without compromising survival outcome. ClinicalTrials.gov Identifiers NCT03015376 (PUMCH-OBGYN-2013), NCT03291236 (SOCM-1).

Neoadjuvant chemotherapy followed by radical hysterectomy for stage IB2-to-IIB cervical cancer: a retrospective cohort study.

INTRODUCTION: This study was to evaluate the surgical and survival effects of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) for cervical cancer with stages IB2 to IIB of FIGO 2009 staging. METHODS: From February 2, 2001 to November 11, 2015, 428 patients received NAC followed by RH in a tertiary hospital, in which all the major procedures were performed by one surgeon. Surgical and survival outcomes were evaluated between the NAC and primary RH groups. RESULTS: A total of 279 (65.2%) patients received NAC, and the overall clinical and complete pathological response rates were 65.9% and 10.8%, respectively. Compared with primary RH patients, NAC patients had more advanced stages, higher recurrence rate, longer median duration of RH, and more median estimated blood loss. After adjusted with baseline risk factors, no significant differences in progression-free or overall survival were observed between the NAC and primary RH groups. However, the responders to NAC had better survival outcomes. CONCLUSIONS: There were no surgical or survival benefits of NAC for patients with cervical cancer of stages IB2 to IIB except for the responders to NAC.

[Clinical study of 16 cases of villoglandular adenocarcinoma of uterine cervix].

OBJECTIVE: To explore the clinicopathologic features, managements and outcomes of villoglandular adenocarcinoma (VA) of uterine cervix. METHODS: From June 2009 to January 2014, a total of 16 cases of VA were reviewed retrospectively. RESULTS: Their mean age was 41.4 (30-56) years. The major symptoms were post-coital hemorrhage or abnormal vaginal hemorrhage (10/16). And the International Federation of Gynecology and Obstetrics (FIGO) stages were Ia1 (n = 1),Ib1 (n = 12),Ib2 (n = 2) and IIa1 (n = 1).One patient of Ia1 stage underwent laparoscopic total hysterectomy and bilateral salpingo-oophorectomy (BSO) after conization; one patient of Ib1 stage total abdominal hysterectomy and BSO after radiotherapy and concurrent chemotherapy while another one of Ib1 stage radical vaginal trachelectomy; one pregnancy-associated patient of Ib1 stage was diagnosed at 12 weeks' gestation and underwent cesarean radical hysterectomy plus pelvic lymphadenectomy after four courses of chemotherapy. Aand the remainder underwent radical hysterectomy plus pelvic lymphadenectomy.None of 14 cases with a known status of lymph node status had positive nodes. And 1/13 cases undergoing ovariectomy had pathologically confirmed cervical cancer metastasis of ovarian surface and the remainder and another patient of ovarian biopsy had negative results for lymph nodes. The median follow-up period was 23.3 (5-60) months. All patients survived and there was one recurrent case of vaginal stump mass at 8 months after initial surgery. The overall and disease-free 5-year survival was 100% and 94% (15/16) respectively. CONCLUSION: VA mainly affects younger women and prognosis is generally fair with a lower rate of ovarian metastasis compared to common forms of cervical cancer. Due to a limited sample size and clinical data are studied retrospectively, multi-center prospective studies are warranted for a better understand of this disease.

Ovarian preservation in young patients with stage I cervical adenocarcinoma: a surveillance, epidemiology, and end results study.

OBJECTIVES: Although a large part of patients with cervical adenocarcinoma are young, oophorectomy is commonly performed in those who receive hysterectomy for fear of ovarian metastasis. The purpose of this study was to examine the safety of ovarian preservation in young women with cervical adenocarcinoma. METHODS: Patients 45 years or younger with stage I cervical adenocarcinoma and adenosquamous carcinoma were identified in the Surveillance, Epidemiology, and End Results program (1988-2007). The characteristics of the patients with ovarian preservation were compared with those of the women with oophorectomy. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to explore the effects of ovarian preservation on survival. RESULTS: The study sample consisted of 1639 women, including 1062 women (64.8%) who underwent oophorectomy and 577 women (35.2%) who had ovarian preservation at the time of hysterectomy. Younger age (P < 0.001), recent diagnosis (P < 0.001), low-grade (P < 0.001) and smaller tumor (P < 0.001), white population (P = 0.015), as well as less chance to undergo lymphadenectomy (P < 0.001) and adjuvant radiotherapy (P = 0.041) were associated with ovarian preservation. Ovarian preservation had no effect on either cancer-specific (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.50-1.61) or overall (HR, 0.81; 95% CI, 0.49-1.33) survival in the Cox proportional hazards model. When the patients without radiotherapy were separately analyzed, the effect on either cancer-specific (HR, 1.24; 95% CI, 0.44-3.54) or overall (HR, 0.77; 95% CI, 0.35-1.73) survival were not statistically significant. CONCLUSIONS: Ovarian preservation may have oncological safety for young women with stage I cervical adenocarcinoma.

[Research advance in antitumor activities of artemisinin and its derivatives].

Artemisinin and its derivatives are highly effective in fighting against malaria. Notably, these drugs have shown potent anti-timor activities by arresting cellular growth, enhancing apoptosis, inhibiting angiogenesis, and regulating the expression of tumor-associated genes, although the underlying mechanisms remain unclear.

Research of the Potential Vaginal Microbiome Biomarkers for High-Grade Squamous Intraepithelial Lesion.

Vaginal microbiome may have a role in HPV infection and cervical neoplasm. To explore potential vaginal microbiome biomarkers for high-grade squamous intraepithelial lesion (HSIL), and to find the best scheme to facilitate the current cervical cancer screening strategy. This study enrolled 272 women, including 83 confirmed with HSIL, 86 with HPV infection but without cervical neoplasm, and 103 without HPV infection as controls. Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. The relative increasing abundance of Stenotrophomonas, Streptococcus, and Pseudomonas, and a concomitant paucity of Dialister, unidentified Prevotellaceae, Faecalibacterium, Bifidobacterium, and Bacteroides, were related with HSIL, which can be used to predict the development of HISL in high-risk HPV infected patients. The relative abundance of Stenotrophomonas being over 0.0090387%, or Faecalibacterium being under 0.01420015%, or Bifidobacterium being under 0.0116183% maybe a good predictor for HSIL for those infected with HPV 16 and/or 18. The relative abundance of Stenotrophomonas being over 0.01549105%, or Streptococcus being over 0.48409585%, or Bacteroides being under 0.0296912% maybe a good predictor for HSIL for those infected with the 12 other high-risk types of HPV with concurrent abnormal TCT results. This study revealed that potential vaginal microbiome biomarkers may relate to HSIL, and can facilitate the cervical cancer screening.

Efficacy of different surgical approaches on survival outcomes in patients with early-stage cervical cancer: protocol for a multicentre longitudinal study in China.

INTRODUCTION: Recent studies have revealed that the oncological survival outcomes of minimally invasive radical hysterectomy (MIRH) are inferior to those of abdominal radical hysterectomy (ARH) in early-stage cervical cancer, but the potential reasons are unclear. METHODS AND ANALYSIS: Each expert from 28 study centres participating in a previously reported randomised controlled trial (NCT03739944) will provide successive eligible records of at least 100 patients who accepted radical hysterectomy for early-stage cervical cancer between 1 January 2009 and 31 December 2015. Inclusion criteria consist of a definite pathological evaluation of stages IA1 (with positive lymphovascular space invasion), IA2 and IB1 according to the International Federation of Gynecology and Obstetrics 2009 staging system and a histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. The primary endpoint is 5-year disease-free survival between the MIRH and ARH groups. The secondary endpoints include the MIRH learning curves of participating surgeons, 5-year overall survival between the MIRH and ARH groups, survival outcomes according to surgical chronology, surgical outcomes and sites of recurrence and potential risk factors that affect survival outcomes. A subgroup analysis in patients with tumour diameter less than 2 cm will follow the similar flow diagram. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Peking Union Medical College Hospital (registration no. JS-1711), and is also filed on record by all other 27 centres. The results will be disseminated through community events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03738969.

Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China.

BACKGROUND: There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China. METHODS: This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up. DISCUSSION: The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility. TRIAL REGISTRATION: ClinicalTrials.gov NCT03739944 . Registered on November 14, 2018.

Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection.

BACKGROUND: Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. METHODS: A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. RESULTS: In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. CONCLUSIONS: A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study.

Little is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

[Complications of hysterectomy: analysis of 162 cases].

OBJECTIVE: To evaluate the complications of different approaches of hysterectomy based on analyzing the records of patients with long post-operative hospitalization. METHODS: The records of 3722 patients undergoing hysterectomy due to benign gynecologic disorders were retrieved. A total of 162 patients with ultra-long post-operative hospitalization (> 9 days defined as delayed discharge) were analyzed to evaluate the complications of hysterectomy. RESULTS: (1) Of 162 patients classified into delayed discharge group, 114 (30.6 per thousand)had post-operative fever in which 82 cases (71.9%) could be explained with complications. (2) The most common procedure-related complications included pelvic hematoma/vaginal stump bleeding (n = 46, 12.4 per thousand), wound dehiscence/infection (n = 24, 6.4 per thousand), organ injury (n = 20, 5.4 per thousand), postoperative urinary retention (n = 20, 5.4 per thousand), postoperative infection(n = 20, 5.4 per thousand)and lower extremity deep venous thrombosis (n = 10, 2.7 per thousand). (3) Organ injury appeared to be relatively more common in abdominal hysterectomy than in laparoscopic and vaginal hysterectomy (7.6 per thousand, 2.1 per thousand and 0 respectively) while pelvic hematoma/vaginal stump bleeding more common in laparoscopic and vaginal hysterectomy than in abdominal hysterectomy (16.5 per thousand, 30.8 per thousand and 7.6 per thousand respectively). (4) Wound dehiscence/infection only occurred in abdominal approach and it was closely related with some concurrent disorders. CONCLUSION: Complications of hysterectomy are related to the approach of surgery, disease characteristics and surgeon experiences. A more accurate evaluation of complications might be performed on the basis of the data of patients with delayed discharge.

[Predictors of residual lesion in cervix after conization in patients with cervical intraepithelial neoplasia and microinvasive cervical cancer].

OBJECTIVE: To determine the clinicopathological factors predicting residual lesions after conization in patients with cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma of cervix (MIC). METHODS: The clinical data of 77 patients with CIN3, 20 patients with stage Ia1 cervical cancer, and 8 patients with stage 1a2 cervical cancer, totally 105 patients, aged (43 + 6), who received further surgery within 3 months after conization, 95 receiving hysterectomy, 2 receiving repeated conization, and 8 receiving radical hysterectomy and pelvic lymph node dissection, were evaluated. The demographic features, clinical and pathological parameters, and the correlation thereof with the post-conization residual lesions were analyzed retrospectively. RESULTS: Residual lesions were found in the specimens obtained from hysterectomy or repeated conization of 53 of the 105 patients (50.5%), among which 38 were CIN2 or less severe lesions. Univariate analysis showed that menopausal status, procreation status, cervical cytology, method of conization, and range of resection were not correlated with the presence of post-conization residual lesion, while age < or = 45 (P < 0.05, odd ratio [OR] = 4.68) and positive resection margin (P < 0.05, OR = 5.40) were risk factors of residual lesion. There were no differences in the proportion of post-conization residual lesion among the patients with MIC, CIN 3, CIN2 or less severe lesions. Multivariate logistic analysis showed that only the positive resection margin was an independent risk factor of residual lesion after conization (P < 0.05, OR = 4.20). CONCLUSIONS: Although severity of the cervical disease is the most important factor in determining post-conization treatment, it is not a predicting factor for post-conization residual lesion. Only the positive resection margin was an independent risk factor of residual lesion after conization.

Surgical, Urinary, and Survival Outcomes of Nerve-sparing Versus Traditional Radical Hysterectomy: A Retrospective Cohort Study in China.

PURPOSE: The purpose of this retrospective study was to compare the surgical, urinary, and survival outcomes between nerve-sparing radical hysterectomy (NSRH) and traditional radical hysterectomy (TRH) for stage IB cervical cancer, in which all the primary procedures were performed by a single physician. METHODS: Patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO) stage IB were included if they received radical hysterectomy of class III or type C in 1 center between February 2001 and November 2015. The epidemiological, clinicopathologic, surgical, and urinary data were collected and compared between the NSRH and TRH groups. The follow-up period ended in December 2016. RESULTS: A total of 406 patients were identified, including 111 (27.3%) in the TRH group and 295 (72.7%) in the NSRH group. Most epidemiological and clinicopathologic characteristics were balanced between the 2 groups. The NSRH and TRH groups had similar mean operating times and comparable short-term postoperative complications, but NSRH had less mean estimated blood loss and a shorter mean postoperative stay (all P <0.001). Within 12 months from surgeries, patients in the NSRH group had less residual urine and fewer urinary dysfunctions. For the 371 patients with definite survival outcomes, in the multivariate analysis, both overall survival (hazard ratio=1.79, 95% confidence interval: 0.64-5.02) and disease-free survival (hazard ratio=1.50, 95% confidence interval: 0.72-3.11, P=0.280) of the NSRH group were similar to those of the TRH group. CONCLUSION: NSRH for stage IB cervical cancer patients had better urinary outcomes than TRH without sacrificing the safety and survival benefits.

The impact of the surgical routes and learning curve of radical hysterectomy on the survival outcomes in stage IB cervical cancer: A retrospective cohort study.

OBJECTIVE: Little is known about the definite reasons of the disadvantage of minimally invasive surgery in the treatment of early stage cervical cancer. This study is to compare survival outcomes of patients with stage IB cervical cancer who received radical hysterectomy (RH) by one surgeon in different periods. METHODS: A retrospective analysis was performed on stage IB cervical cancer patients who received RH from February 2001 to November 2015 at a tertiary hospital. All the major procedures were performed by one surgeon. The clinicopathological characteristics and survival outcomes were compared with laparoscopic RH (LRH) and abdominal RH (ARH) groups in the periods of 2001-2005, 2006-2010, and 2011-2015. RESULTS: Totally 406 patients were included in the study, 135 (33.3%) and 271 (66.7%) in ARH and LRH groups respectively. The 5-year disease-free survival (DFS) of all patients increased from 2001 to 2005 to 2006-2010 but decreased in 2011-2015. No significant differences exist in the 5-year DFS and overall survival (OS) rates in the first 50 patients of LRH and ARH groups. The subgroup analysis in stage IB1 patients (68.2% of all participants) reached the same conclusions. CONCLUSION: For RH patients, in which all major procedures were performed by one surgeon, the DFS did not exhibit substantial improvement in the period of 2001-2015 since the extensive adoption of LRH. The learning curve probably explains the disadvantage of LRH.

The prophylactic effects of long-acting granulocyte colony-stimulating factor for febrile neutropenia in newly diagnosed patients with epithelial ovarian cancer: a randomised controlled study.

OBJECTIVE: This study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC). METHODS: Patients were randomised into a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF for first cycle and treatment per physician discretion for subsequent cycles) at a ratio of 1:2. The incidences of FN and myelosuppression and the number of clinical visits, medication doses, complete blood count (CBC) tests and adverse events were compared between the two groups. A regression model was used to determine the risk factors for FN. RESULTS: From 30 November 2018 to 1 April 2019, 84 cases were included in the final analysis; there were 24 (28.6%) and 60 (71.4%) patients in the study and control groups, respectively, and 605 chemotherapy cycles. The study group or chemotherapy cycles utilising long-acting G-CSF had significantly fewer utilisations and doses of short-acting G-CSF; clinical visits; CBC tests; and incidences of FN and myelosuppression; and less G-CSF-associated pain. The utilisation of G-CSF was the only independent factor for FN in a binary regression model. CONCLUSION: Long-acting G-CSF could effectively reduce the incidences of FN and myelosuppression and had mild adverse effects in newly diagnosed patients with EOC receiving chemotherapy. TRIAL REGISTRATION NUMBER: NCT03740464.

Laparoscopic vs. Abdominal Radical Hysterectomy for Locally Advanced Cervical Cancer.

This study is to compare the survival outcomes of laparoscopic radical hysterectomy (LRH) to those of abdominal radical hysterectomy (ARH) for patients with locally advanced cervical cancer (LACC). Patients with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IIB LACC who underwent radical hysterectomy between 2001 and 2015 were identified. The disease-free survival (DFS) and overall survival (OS) were compared according to the surgical approach and were adjusted based on clinicopathologic characteristics. A total of 396 patients were included in the study, with 179 (45.2%) and 217 (54.8%) patients in the ARH and LRH groups, respectively. The LRH group showed a significantly lower amount of estimated blood loss, lower blood transfusion rate and shorter length of hospital stay. Overall, there were no significant differences in the 5-year DFS and 5-year OS between the LRH and ARH groups with the Kaplan-Meier method. However, multivariate analyses identified LRH as an independent prognostic factor for a poor DFS (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 0.19 to 0.87; p = 0.02). The analysis of stage IB2 disease and the squamous subtype (61.9% and 87.9% of all participants, respectively) reached the same conclusion. When stratifying by FIGO stage, the patients with IB2 (n = 348) in the ARH group had a significantly better DFS (HR 0.14, 95% CI 0.05-0.42, p < 0.01) and OS (HR 0.17, 95% CI 0.04-0.67, p = 0.11) than those in the LRH group in the Cox regression model. However, no differences were found in patient with stage IIA1, IIA2, or IIB in Cox regression model. When stratifying by histological types, for the patients with squamous carcinomas (n = 375), in Cox model, ARH had a significantly superior DFS compared with those who underwent LRH (HR 0.45, 95% CI 0.25-0.82, p = 0.01), but the OS was not statistically significant (HR 0.57, 95% CI 0.27-1.20, p = 0.14). However, no differences were found in patient with adenocarcinoma and adenosquamous carcinomas in the Cox model. Therefore, ARH was associated with a higher DFS than LRH in patients with LACC, especially in patients with stage IB2 disease or the squamous subtype.

Hollow mesoporous ruthenium nanoparticles conjugated bispecific antibody for targeted anti-colorectal cancer response of combination therapy.

Combined treatment based on tumor-targeted nanoparticles has become one of the most promising anticancer strategies. Moreover, bispecific antibodies have been designed as linkers to promote the interaction between natural killer (NK) cells and tumor cells, while triggering NK cell-mediated target cell lysis. Here, we adopted a novel design that uses PEGylated hollow mesoporous ruthenium nanoparticles as a carrier to load the fluorescent anti-tumor complex ([Ru(bpy)2(tip)]2+, RBT) and a conjugate with bispecific antibodies (SS-Fc). By accurately targeting carcinoembryonic antigen overexpressed in colorectal cancer cells, HMRu@RBT-SS-Fc significantly improved selective penetration in vitro. The functionalized nanocomplex effectively engaged NK cells and possessed excellent near infrared-sensitive cytotoxicity. Systematic in vivo studies clearly demonstrated the high tumor targeting and anticancer activity in heterotopic colorectal tumor model via combined photothermal and immune therapy. This nanosystem establishes a new platform for future image-guided drug delivery and highly efficient cancer therapy.

Efficacy of different surgical approaches in the clinical and survival outcomes of patients with early-stage cervical cancer: protocol of a phase III multicentre randomised controlled trial in China.

INTRODUCTION: In the last three decades, minimally invasive surgery (MIS) for radical hysterectomy (RH) has become a popular treatment option for early-stage cervical cancer. However, a recently published randomised controlled trial (LACC trial) and an epidemiological study in the USA revealed strong evidence against the survival advantage of MIS for RH. However, the influencing factors of research centres and the learning curves of surgeons in these studies lacked sufficient evaluation. The efficacy of different surgical approaches for early-stage cervical cancer in the clinical and survival outcomes remains to be validated. METHODS AND ANALYSIS: Patients diagnosed with FIGO (2009) stage IA1 (with lymphovascular space invasion), IA2 or IB1 cervical cancer with histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma will be recruited in this multicentre randomised controlled study. Patients will be randomly assigned to undergo MIS (robot-assisted or laparoscopic RH) or abdominal RH. Within 2 years, 1448 patients in 28 centres in China will be recruited to meet the criteria of a non-inferiority threshold of HR of 1.6 with bilateral nominal α <0.05 and power of 0.8. All surgeries will be performed by the indicated experienced surgeons. At least 100 RH cases in the individual past one decade of practice will be analysed as proof of learning curves. The primary objective of this study is 5-year disease-free survival. The secondary objectives include the overall survival rate, progression-free survival rate, disease-free survival rate, cost-effectiveness and quality of life. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Peking Union Medical College Hospital and is filed on record by all other centres. Written informed consent will be obtained from all eligible participants before enrolment. The results will be disseminated through community events, academic conferences, student theses and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03739944.

Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study.

BACKGROUND: Multiple targeted gene sequencing is seldom performed in both germline and somatic testing for ovarian cancer. This study is to evaluate the specific genetic alterations, including both somatic and germline mutations, in Chinese patients with epithelial ovarian cancer (EOC) in a prospective cohort study. MATERIALS AND METHODS: Mutations in a customed 21-gene panel that included BRCA1, BRCA2, and 19 other tumor suppressor genes related to homologous recombination (HR) deficiency or non-HR deficiency were detected by targeted exon capture and next-generation sequencing (NGS) technology across all coding exons and exon-intron (±20 base pairs) boundaries. Patients were enrolled consecutively and unselectively without age or family history consideration. Sixty-two unselected patients with epithelial ovarian cancer were enrolled in our study to be tested for paired somatic and germline mutations. All patients were tested using a 21-gene panel that included BRCA1, BRCA2, CHEK2, PALB2, BRIP1, TP53, PTEN, STK11, CDH1, ATM, BARD1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, RAD50, and RAD51C. RESULTS: Mutation analysis revealed that 77.4% (48/62) of patients carried one or more of 64 identified genetic alterations, including 19 germline and 45 somatic deleterious mutations. Twelve individuals shared both germline and somatic mutations. BRCA mutants existed in 17 of 62 (27.4%) patients. Of the 64 mutations detected, 46 (74.2%) were in 7 other HR or non-HR genes, including TP53, PTEN, ATM, CHEK2, PALB2, RAD51C, and STK11. In somatic mutation analysis, TP53 showed frequent pathogenic or likely pathogenic mutations in 56.5% (35/62) of enrolled cases, among which six cases harbored a loss of heterozygosity. CONCLUSIONS: This is the first report of multi-gene panel testing for germline and somatic mutations among Chinese EOC patients, which revealed a broader deleterious variants than only BRCA testing. REGISTRATION: Registration No. NCT03015376, clinicaltrials.gov , registered on January 10, 2017.