The inhibition of YTHDF3/m6A/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.

The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.

Clinical application of a fixed reference line in the ultrasound quantitative diagnosis of female pelvic organ prolapse.

OBJECTIVE: This study explored using an improved ultrasound (US) for quantitative evaluation of the degree of pelvic organ prolapse(POP). DESIGN: A transluminal probe was used to standardize ultrasound imaging of pelvic floor organ displacements. A US reference line was fixed between the lower edge of the pubic symphysis and the central axis of the pubic symphysis at a 30°counterclockwise angle. METHOD: Points Aa, Ba, C and Bp on pelvic organ prolapse quantification (POP-Q) were then compared with the points on pelvic floor ultrasound (PFUS). RESULTS: One hundred thirteen patients were included in the analysis of the standard US plane. Correlations were good in the anterior and middle compartments (PBN:Aa, ICC = 0.922; PBB:Ba, ICC = 0.923; and PC:C, ICC = 0.925), and Bland-Altman statistical maps corresponding to the average difference around the 30°horizontal line were close to 0. Correlations were poor in the posterior compartment (PRA:Bp, ICC = 0.444). However, eight (7.1%) cases of intestinal hernia and 21 (18.6%) cases of rectocele were diagnosed. CONCLUSIONS: Introital PFUS using an intracavitary probe, which is gently placed at the introitus of the urethra and the vagina, may be accurately used to evaluate organ displacement. The application of a 30°horizontal line may improve the repeatability of the US diagnosis of POP.

NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer.

Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by the groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 antibodies. N4-acetylcytidine (ac4C) modification, catalyzed by NAT10, is an important posttranscriptional modification of mRNA in cancers. However, its impact on immunological dysregulation and the tumor immunotherapy response in CCa remains enigmatic. Here, a significant increase in NAT10 expression in CCa tissues is initially observed that is clinically associated with poor prognosis. Subsequently, it is found that HOXC8 activated NAT10 by binding to its promoter, thereby stimulating ac4C modification of FOXP1 mRNA and enhancing its translation efficiency, eventually leading to induction of GLUT4 and KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted in increased glycolysis and a continuous increase in lactic acid secretion by CCa cells. The lactic acid-enriched tumor microenvironment (TME) further contributed to amplifying the immunosuppressive properties of tumor-infiltrating regulatory T cells (Tregs). Impressively, NAT10 knockdown enhanced the efficacy of PD-L1 blockade-mediated tumor regression in vivo. Taken together, the findings revealed the oncogenic role of NAT10 in initiating crosstalk between cancer cell glycolysis and immunosuppression, which can be a target for synergistic PD-1/PD-L1 blockade immunotherapy in CCa.

The oncological and obstetric results of radical trachelectomy as a fertility-sparing therapy in early-stage cervical cancer patients.

PURPOSE: This study explored the oncological and obstetric results of radical trachelectomy (RT) in early-stage cervical cancer patients. METHODS: A retrospective analysis was conducted the oncological and obstetric results of 23 patients with early cervical cancer (stages IA2-IB3; International Federation of Gynecology and Obstetrics, 2018) who underwent RT in The Maternal and Child Health Care Hospital of Guiyang, China, from October 2004 to September 2018. RESULTS: 23 patients had cervical tumors of the squamous cell carcinoma histological type. All 23 patients retained reproductive function. The mean follow-up time was 112.87 ± 55.75 (36-199) months. The median tumor size was 2.00 ± 1.35 cm (imperceptible to the eyes 5.00 cm). No recurrence was observed in any of the patient cases. Among the patients with a tumor size > 4 cm (up to 5 cm), three patients who wished to preserve fertility accepted RT following neoadjuvant chemotherapy The pregnancy outcomes were as follows: 8 cases (47.06%) out of 17 cases who attempting pregnancy conceived 12 times.First-trimester abortion and the voluntary abandonment of pregnancy occurred in 4 cases (33.33%), respectively, one patient performed deliberate termination at 24 weeks of gestation. Second-trimester abortion occurred in three cases (25.0%) for chorioamnionitis. Premature delivery at 32 weeks occurred in one case (8.33%). CONCLUSION: Radical trachelectomy is a safe and effective treatment for women with early-stage cervical cancer preserving fertility biology. Patients with a cervical tumor sized > 4 cm can be pregnant after neoadjuvant chemotherapy and RT. Accordingly, this treatment is worthy of further exploration.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study.

PURPOSE: To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. METHOD: We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. RESULTS: In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). CONCLUSION: Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

The Effect of Laparoscopic Radical Hysterectomy Surgical Volume on Oncology Outcomes in Early-Stage Cervical Cancer.

Purpose: To examine the association between surgical volume and surgical and oncological outcomes of women with stage IB1 cervical cancer who underwent laparoscopic radical hysterectomy (LRH). Methods: We retrospectively analyzed the oncological outcomes of 1,137 patients with stage IB1 cervical cancer receiving LRH from 2004 to 2016. The surgical volume for each surgeon was defined as low [fewer than 50 surgeries, n = 392(34.5%)], mid [51-100 surgeries, n = 315(27.7%)], and high [100 surgeries or more, n = 430(37.8%)]. Surgical volume-specific survival was examined with Kaplan-Meier analysis, multivariable analysis, and propensity score matching. Results: The operative times of the high-volume group (227.35 ± 7.796 min) were significantly shorter than that of the low- (272.77 ± 4.887 min, p < 0.001) and mid-volume (255.86 ± 4.981 min, p < 0.001) groups. Blood loss in the high-volume group (169.42 ± 8.714 ml) was significantly less than that in the low-volume group (219.24 ± 11.299 ml, p = 0.003). The 5-year disease-free survival (DFS) and overall survival (OS) in the low-volume, mid-volume, and high-volume groups were similar (DFS: 91.9, 86.7, and 89.2%, p = 0.102; OS: 96.4, 93.5, and 94.2%, p = 0.192). Multivariable analysis revealed surgical volume was not an independent risk factor for OS or DFS. The rate of intraoperative and postoperative complications was similar among the three groups (p = 0.210). Conclusions: Surgical volume of LRH may not be a prognostic factor for patients with stage IB1 cervical cancer. Surgery at high-volume surgeon is associated with decreased operative time and blood loss.

Impact of neoadjuvant chemotherapy on the postoperative pathology of locally advanced cervical squamous cell carcinomas: 1:1 propensity score matching analysis.

OBJECTIVE: To assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma. METHODS: Postoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy. RESULTS: After 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P < 0.001) in the NACT group were significantly lower than those in the URH group, while the positive rates of parametrial invasion, lymph node metastasis, and vaginal margin invasion were not significantly different between the two groups. The rate of positive lymph node metastasis in the chemotherapy-sensitive group was significantly lower than that in the URH group (18.1% vs 26.5%, P = 0.037). CONCLUSION: Among patients with stage IB2 and IIA2 cervical squamous cell carcinomas, NACT can reduce the positive rate of intermediate-risk factors, such as deep cervical stromal invasion and LVSI, but cannot reduce the positive rate of high-risk factors. For patients who are chemotherapy sensitive, NACT can reduce the positive rate of lymph node metastasis.

Risk factors and long-term impact of urologic complications during radical hysterectomy for cervical cancer in China, 2004-2016.

OBJECTIVE: The primary objective was to describe the incidence and risk factors of urologic complications during radical hysterectomy for cervical cancer. The secondary objective was to investigate the impact of urologic complications on long-term survival. METHODS: Patients who underwent radical hysterectomy for cervical cancer from 2004 to 2016 were identified in the MSCCCC (Major Surgical Complications of Cervical Cancer in China) database. Data on demographic characteristics, clinical characteristics, hospital characteristics and urologic complications were collected. Multivariable logistic regression was used to assess the risk factors of urologic complications and Cox proportional hazards models were performed to identify prognostic factors. RESULTS: A total of 21,026 patients undergoing radical hysterectomy for cervical cancer were identified. The incidence of any urologic complications was 1.54%: 83 (0.39%) ureteral injuries, 17 (0.08%) bladder injuries, 1 (0.005%) ureteral injury combined with bladder injury, and 223 (1.05%) genitourinary fistulas. In a multivariable analysis, surgery at a women and children's hospital (OR = 2.26, 95% CI 1.47-3.48), surgery at a facility in a first-tier city (OR = 2.08, 95% CI 1.24-3.48), and laparoscopic surgery (OR = 4.68, 95% CI 3.44-6.36) were associated with a higher risk of urologic complications. Cox proportional hazards models revealed that the occurrence of urologic complications was a significant predictor of 2-year overall survival (OR = 1.78, 95% CI = 1.09-2.92), but was not a predictor of 5-year overall survival (OR = 1.27, 95% CI = 0.83-1.94). CONCLUSION: The incidence of urologic complications during radical hysterectomy is low. The risk of urologic complications may be higher for patients who are treated at a women and children's hospital, are treated in first-tier city hospitals, and receive laparoscopic surgery. Urologic complications have an impact on short-term survival, but not on long-term survival.

Transition of the abnormal Savda syndrome to the hepatic carcinoma shifted unfolded protein response to autophagy was partly reversed by Savda Munziq in a rat model.

OBJECTIVES: In Uighur medicine, abnormal Savda Munziq (AMSq) is an adjuvant therapy for cancer patients with abnormal Savda syndrome (ASS) who exhibit the highest degree of pathogenicity and malignancy. The aim of the study was to understand the role(s) of AMSq in cancer patients with ASS. METHODS: A total of 125 rats were divided into groups: control (NC) (n = 15), ASS (n = 25), ASS with hepatic carcinoma (ASSHC) (n = 25) as well as ASSHC treated with low dose (ASSHC-L, n = 20), medium dose (ASSHC-M, n = 20) and high dose (ASSHC-H, n = 20) AMSq. Changes in the unfolded protein response (UPR) and autophagy were analyzed by RT profiler PCR array kits, which covered 84 UPR and 84 autophagy related genes. Protein expression analyses of LC3B, ATG8, GRP78 and CHOP were carried out using western blotting. RESULTS: CHOP and GRP78 expression was enhanced in ASS and ASSHC compared to NC rats and further increased AMSq dose-dependently, indicating an UPR triggering effect of AMSq. The ratios of ATG8/LCB3II-LCB3I protein were reduced in ASSHC rats, an effect which was partly reversed by AMSq. Compared to NC rats in the ASS group, 24 UPR genes were significantly upregulated and 3 downregulated, whereas only 5 autophagy genes were significantly upregulated and 5 downregulated. Compared to NC rats in the ASSHC group, 15 UPR genes were significantly upregulated and 10 downregulated, whereas 16 autophagy genes were significantly upregulated and 8 downregulated. The RT profiler data indicated a shift from UPR in the ASS to the autophagy response in ASSHC rats. ASMq effects on ASSHC rats comprised significant downregulation of 10 autophagy and 2 UPR genes. CONCLUSION: The transformation into hepatic cancer cells included a shift from endoplasmic reticulum stress-related UPR to autophagy gene activation, an effect which could be partly reversed by ASMq.

Tigecycline-induced coagulopathy: a literature review.

Background Several adverse reactions to tigecycline, which is widely used in patients with severe infections, have been documented. Coagulopathy is a lesser known side effect of tigecycline. Aim of the review We summarize the characteristics, possible mechanisms, and treatment of tigecycline-induced coagulopathy. Method PubMed, Ovid, Embase, ISI Web of Knowledge, CNKI, and Wanfang were searched up to March 5, 2019. All articles concerning coagulopathy induced by tigecycline were included. The article types and languages were not limited. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results Ultimately, 17 articles were targeted, including 13 case reports and 4 retrospective observational studies. Tigecycline-induced coagulopathy usually manifests as the dose-dependent prolongation of prothrombin time and activated partial thromboplastin time and a reduction in the fibrinogen level. Tigecycline and its metabolites may have multiple effects on coagulation, influencing the extrinsic or intrinsic pathway and even the common pathway. There is no specific treatment for tigecycline-induced coagulopathy, but it can be reversed by withdrawing tigecycline. Conclusion Tigecycline acts on the coagulation system in a dose-dependent manner, and the most severe adverse event is bleeding. Overdose and prolonged use should be avoided, suspected coagulopathy must be recognized in time, and tigecycline should be withdrawn to prevent severe adverse events. Also, drug clearance disorders can develop in patients with liver and/or renal dysfunction. For patients with severe hepatic or renal impairment, the maintenance dose should be reduced, and indicators of coagulation function should be closely monitored.

Clinical outcomes after colchicine overdose: A case report.

RATIONALE: Colchicine can inhibit cell division and intracellular transport in affected organs by fixing intracellular tubulin and preventing its polymerization into microtubules. A lethal dose of colchicine is considered to be 0.8 mg/kg. The wide distribution of colchicine through 70% of the body following an overdose makes it difficult to eliminate. PATIENT CONCERNS: A 56-year-old man with a clear history of colchicine overdose was admitted to our hospital nearly 40 hours after taking 12 mg (0.17 mg/kg) of colchicine. He had a history of gout and chronic kidney disease. As the disease progressed, he showed most of the clinical manifestations and pathological features of colchicine overdose. DIAGNOSES AND INTERVENTIONS: Colchicine overdose was clear, with symptoms of multiple organ failure including primary gastrointestinal failure, bone marrow hematopoietic inhibition, rhabdomyolysis, cardiac damage, hepatocyte damage. The patient developed secondary septic shock, renal failure, circulatory failure, and respiratory failure. We performed continuous renal replacement therapy and gastric lavage, and administered norepinephrine, frozen plasma, proton-pump inhibitors, adenosylmethionine, antibiotics, granulocyte colony stimulating factor, and total parenteral nutrition. OUTCOMES: The patient rapidly developed complete hematopoietic function inhibition, gastrointestinal failure, and cardiac damage 32 hours after admission. Sustained severe infection and circulatory instability caused a progressive deterioration of respiratory function. Tracheal intubation was performed but the patient continued to deteriorate, and death occurred approximately 132 hours after admission. LESSONS: Excessive colchicine levels cause continuous organ damage due to extensive tissue distribution, eventually leading to multiple organ failure. Colchicine metabolism is delayed in patients with liver or kidney dysfunction, and even a low dose of colchicine may result in poisoning in these individuals. Early diagnosis and reduction of colchicine levels is critical to improve prognosis, and colchicine poisoning should be considered in patients with poor liver or kidney function even when the ingested dose is low.

Staging early cervical cancer in China: data from a multicenter collaborative.

BACKGROUND: In 2018 the International Federation of Gynecology and Obstetrics (FIGO) revised the staging system of cervical cancer. This study aimed to assess the quality of staging early cervical cancer in China before the revision. METHODS: This multicenter retrospective study included 34 tertiary hospitals in China. Medical records of patients with cervical cancer who underwent primary surgical treatment between January 2010 and December 2015 were reviewed retrospectively. All patients were clinically staged according to the 2009 FIGO staging system. Eligibility criteria included: histopathologically confirmed cervical cancer; 2009 FIGO stage IA-IIA2 based on 2009 FIGO staging system; primary surgical treatment including extrafascial, type II or type III radical hysterectomy; radical trachelectomy; with or without pelvic lymphadenectomy; regardless of surgical route via laparotomy or laparoscopy; and complete clinical and pathological data. Patients who received non-surgical treatment, neoadjuvant treatment, or those with incomplete data were excluded. The accuracy of clinical staging was assessed by comparison between clinical and pathologic stage using the latter as the reference standard. RESULTS: A total of 23 933 cases of cervical cancer were identified and 12 681 fulfilled the inclusion criteria. Of these patients, 69.6% were staged accurately, 9.4% were clinically understaged, and 21.0% were clinically overstaged. The accuracy of stage IA, IB1, IB2, IIA1, and IIA2 was 90.0%, 87.5%, 57.4%, 20.3%, and 25.5%, respectively. The causes of stage inaccuracy were as follows: vaginal involvement (62.3%), maximal tumor diameter (24.6%), extent of cervical stromal invasion (7.1%), parametrial invasion (5.8%), bladder or rectal infiltration (0.1%), and distant metastases (0.1%). CONCLUSION: The accuracy of staging early cervical cancer in China was suboptimal before the revision of the staging system, especially for IIA1 and IIA2. The most common reasons for staging inaccuracy were vaginal involvement and tumor diameter.

Impact of pelvic MRI in routine clinical practice on staging of IB1-IIA2 cervical cancer.

Purpose: To evaluate the impact of pelvic magnetic resonance imaging (MRI) on staging of IB1-IIA2 cervical cancer in routine clinical practice. Patients and Methods: A total of 1,016 patients with IB1-IIA2 cervical cancer who underwent primary surgery and preoperative pelvic MRI between January 2009 and December 2015 were identified in a retrospective multicentre study. Data on clinical stage, MRI reports and surgicopathologic findings were extracted from medical records. The impact of MRI on clinical staging was evaluated by comparison before and after combination of MRI. Using surgicopathologic findings as the reference standard, the impact of pelvic MRI on the accuracy of clinical staging was evaluated. Furthermore, the impact on the accuracy of individual staging parameters such as maximal tumor diameter, vaginal involvement or parametrial infiltration were also evaluated. Results: After combination of pelvic MRI, clinical stage remained unchanged in 59.7%, upstaged in 17.2%, and downstaged in 23.0% of the patients. The overall accuracy of clinical staging increased from 61.0% to 81.4% in our study (P<0.05). As for individual staging parameters, the area under the curve (AUC) for maximal tumor diameter increased from 0.58 to 0.81 (P<0.05). However, the AUC for vaginal involvement decreased from 0.61 to 0.57 (P>0.05). The AUC for parametrial infiltration was also suboptimal (AUC=0.56, P<0.05). Conclusion: In routine clinical practice, MRI could increase the overall accuracy of clinical staging in IB1-IIA2 cervical cancer. For staging parameters, it only significantly increased the accuracy of maximal tumor diameter.

LncRNA MALAT1 promotes proliferation and metastasis of cervical cancer cell via regulating miR-124-3p/IGF2BP1 axis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanism of lncRNA MALAT1 modulating proliferation and metastasis of cervical cancer cells via regulating miR-124-3p/IGF2BP1 axis. Methods: A total of 45 cases of cervical cancer tissues and corresponding paracancerous tissues resected from patients, who were admitted to the Department of Obstetrics and Gynecology of Guiyang Maternal and Child Health Hospital during April 2014 and December 2017, were included in this study; in addition, cervical cancer cell lines SiHa, Caski, HeLa and C33awere also collected for this study. qPCR was applied to detect the expression of MALAT1 in cervical cancer tissues and cell lines. MALAT1-knockdown vectors, miR-124-3p inhibitors and IGF2BP1-overexpression vectors were constructed and used to transfect cervical cancer cells, respectively; the influence of MALAT1 or MALAT1 knockdown on cell proliferation, invasion and epithelial mesenchymal transition (EMT) via miR-124-3p/IGF2BP1 axis were determined by CCK-8 assay, Transwell assay, Wb and immunofluorescence, respectively. The interaction between MALAT1, miR-124-3p, and IGF2BP1 were verified by dual luciferase reporter gene assay. Results: MALAT1 was up-regulated in cervical cancer tissues and cell lines (P<0.05 or P<0.01). Meanwhile, MALAT1 knockdown remarkably inhibited proliferation, invasion and EMT of cervical cancer cells (P<0.05 or P<0.01). Moreover, dual-luciferase reporter gene assay showed that MALAT1 directly interacted with miR-124-3p and down-regulated its expression, while miR-1243p negatively regulated IGF2BP1 expression. Our experiment further validated that MALAT1 knockdown suppressed proliferative, invasion and EMT of cervical cancer cells via inducing the inhibitory effect of miR-124-3p on IGF2BP1 (P<0.05 or P<0.01). Conclusion: MALAT1 promotes the proliferation, invasion and EMT of cervical cancer cells by down-regulating miR-124-3p/IGF2BP1 axis, which provides potential molecular targets for early diagnosis or treatment of cervical cancer.

Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma.

BACKGROUNDS: A large number of studies have reported the relationships between serum lactate dehydrogenase (LDH) and prognosis of osteosarcoma. However, the result is still controversial and no consensus has been reached. Therefore, we performed a meta-analysis to evaluate the prognostic role of serum LDH in osteosarcoma patients. METHODS: We performed the systematic computerized search for eligible articles from PubMed, Embase, and Cochrane databases until December 21, 2017. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) of overall survival (OS) and event-free survival (EFS) were obtained to assess the prognostic value of serum LDH. RESULTS: A total of 18 studies with 2543 osteosarcoma patients were included. Overall, 15 studies assessed the elevated serum LDH level on OS and the pooled HR was 1.87 (95% CI = 1.58-2.20). Meanwhile, the pooled HR to evaluate the relationship between serum LDH and EFS in 9 studies was 1.78 (95% CI = 1.51-2.10). The same results were acquired when these studies were stratified by Enneking stage, geographic region, and sample size. No heterogeneity existed between these subgroups (P > .05). Begg's funnel plot and Egger's test (OS: P = .04; EFS: P = .34) showed that possible publication bias might exist in OS studies. Sensitivity analysis suggested the pooled HR was robust. CONCLUSIONS: This meta-analysis demonstrates that elevated serum LDH level is apparently associated with lower EFS rate and serum LDH could be a prognostic biomarker for osteosarcoma patients.

Forecast of actin-binding proteins as the oncotarget in osteosarcoma - a review of mechanism, diagnosis and therapy.

Osteosarcoma (OS) is the most common bone malignant tumor with a high rate of lung metastasis and principally emerges in children and adolescents. Although neoadjuvant chemotherapy is widely used around the world, a high rate of chemoresistance occurs and frequently generates a poor prognosis. Therefore, finding a new appropriate prognostic marker for OS is a valuable research direction, which will give patients a better chance to receive proper therapy. Actin-binding proteins (ABPs) are a group of proteins that interact with actin cytoskeleton and play a crucial role in the regulation of the cell motility and morphology in eukaryotes. Meanwhile, ABPs also act as a bridge between the cytomembrane and nucleus, which transmit the outside-in and inside-out signals in cytoplasm. Furthermore, ABPs alter the dynamic structure of actin and regulate the invasion and metastasis of cancer. Hence, ABPs have a wide application in predicting the prognosis, and may be new targets, in tumor therapy. This review focuses on a series of ABPs and discusses their modulatory functions. It provides a new insight into the classification of ABPs' functions in the process of invasion and metastasis in OS and illuminates the potential ability in predicting the prognosis of OS patients.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

Reevaluation of the effect of lamivudine therapy preoperative to prevent HBV recurrence after liver transplantation.

BACKGROUND: Hepatitis B virus (HBV) recurrence may result in hepatic insufficiency or dysfunction of liver grafts. This study was to reevaluate the preventive effect of lamivudine therapy pretransplant on HBV recurrence after liver transplantation with combined lamivudine and hepatitis B immunoglobulin (HBIG) as a prophylactic regimen. METHODS: This is a single-center, retrospective study of 122 liver transplant recipients operated on from January 2002 to September 2006 at our hospital. All subjects showed positive hepatitis B surface antigen (HBsAg) and HBV DNA in blood, without HBV mutation in YMDD at the time of liver transplantation. The protocol with combined lamivudine and HBIG for preventing HBV recurrence was used on the day of operation. The initial immunosuppression therapy was identical. After one year follow-up, the recipients were divided into 2 groups: patients without HBV recurrence (group I) and patients with HBV recurrence (group II). Preoperative lamivudine therapy and postoperative mycophenolate mofetil (MMF) and glucocorticoid therapy were analyzed using the Wilcoxon's test and Stepwise logistic regression method. RESULTS: In the HBV recurrence group, the duration of pre-transplant lamivudine administration was significantly longer than that in the without HBV recurrence group (Z=-4.424, P=0.000). The HBV recurrence rate was significantly higher in patients with preoperative lamivudine therapy than in patients without lamivudine therapy (X2=13.11, P=0.000); the risk of HBV recurrence increased by a 10.909-fold in patients with pre-transplant lamivudine therapy compared with that in patients without lamivudine therapy (OR=10.909; 95% CI for OR: 2.86-41.67). Seven (63.6%) of 11 HBV recurrence recipients had YMDD mutants. The duration of MMF or glucocorticoid was not different between the 2 groups (Z(MMF)=-1.453, P(MMF)=0.146; Z(Pre)=-0.795, P(Pre)=0.427). No significant difference was noted in the HBV recurrent rate in patients with MMF duration < or =6 and >6 months (X2=0.185, P=0.667), as it was in patients with prednisone therapy < or =3 and >3 months (X2=0.067, P=0.793). CONCLUSIONS: With the protocol of combined lamivudine and HBIG for preventing HBV recurrence in liver transplantation recipients, liver transplantation candidates with positive HBV DNA should not be subjected to preoperative administration of lamivudine. A high dose of HBIG during the ahepatic period and in the early stage of post-transplantation can fulfill the treatment target as a long-term lamivudine therapy before liver transplantation. Long-term preoperative lamivudine treatment may result in an earlier HBV mutation in YMDD and increase the HBV recurrence rate and risk in the first year after transplantation.

Long-term outcome of combined liver-kidney transplantation: a single-center experience in China.

BACKGROUND/AIMS: To evaluate patient survival with combined liver-kidney transplantation (CLKT) and to identify factors of death in these patients. METHODOLOGY: Among 554 cases of liver transplantations (LTs) performed between January 1999 and October 2006, there were 19 cases (3.43%) of CLKT recipients. To compare the patient survival, 50 matched LT patients out of these patients were analyzed retrospectively. Furthermore, causes of death in CLKT patients were investigated. RESULTS: Within a mean follow-up of 25.2 months (range 1-96 months), 7 CLKT patients had died (mortality: 36.8%). There were 4 (21.1%) that died in hospital within 1 month, and 3 late mortality cases (deceased after hospital discharge). Actuarial survival was 73.7% at 1 year, 59.5% at 3 years, and 59.5% at 5 years. Cumulative patient survival was significantly worse among CLKT patients compared with LT patients. After excluding patients who died during the first month in the 2 groups, cumulative patient survivals were comparable between the 2 groups. The survival rate in CLKT patients was 87.5% at 1 year, 70.7% at 3 years, and 70.7% at 5 years. CONCLUSIONS: CLKT has relatively high hospital mortality as compared to LT. Beyond the hospital discharge, however, the long-term survival does not differ from LT.