Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Establishment and validation of a prediction model for gestational diabetes.

AIM: To develop a visual prediction model for gestational diabetes (GD) in pregnant women and to establish an effective and practical tool for clinical application. METHODS: To establish a prediction model, the modelling set included 1756 women enrolled in the Zunyi birth cohort, the internal validation set included 1234 enrolled women, and pregnant women in the Wuhan cohort were included in the external validation set. We established a demographic-lifestyle factor model (DLFM) and a demographic-lifestyle-environmental pollution factor model (DLEFM) based on whether the women were exposed to environmental pollutants. The least absolute shrinkage and selection lasso-logistic regression analyses were used to identify the independent predictors of GD and construct a nomogram for predicting its occurrence. RESULTS: The DLEFM regression analysis showed that a family history of diabetes (odd ratio [OR] 2.28; 95% confidence interval [CI] 1.05-4.71), a history of GD in pregnant women (OR 4.22; 95% CI 1.89-9.41), being overweight or obese before pregnancy (OR 1.71; 95% CI 1.27-2.29), a history of hypertension (OR 2.61; 95% CI 1.41-4.72), sedentary time (h/day) (OR 1.16; 95% CI 1.08-1.24), monobenzyl phthalate (OR 1.95; 95% CI 1.45-2.67) and Q4 mono-ethyl phthalate concentration (OR 1.85; 95% CI 1.26-2.73) were independent predictors. The area under the receiver operating curves for the internal validation of the DLEFM and the DLFM constructed using these seven factors was 0.827 and 0.783, respectively. The calibration curve of the DLEFM was close to the diagonal line. The DLEFM was thus the more optimal model, and the one which we chose. CONCLUSIONS: A nomogram based on preconception factors was constructed to predict the occurrence of GD in the second and third trimesters. It provided an effective tool for the early prediction and timely management of GD.

Characteristics of exposure to 10 polycyclic aromatic hydrocarbon metabolites among pregnant women: cohort of pregnant women in Zunyi, southwest China.

OBJECTIVE: Our aim was to elucidate the polycyclic aromatic hydrocarbon (PAH) metabolites exposure levels of pregnant women in the underdeveloped region of Zunyi, southwest China. METHODS: Sociodemographic information was collected via questionnaires, and urine samples were collected at the same time. A total of 3047 pregnant women participated in the study. Gas chromatography/mass spectrometry was used to detect the urine concentrations of 10 PAH metabolites. A generalised linear model (GLM) was used to identify predictive factors of PAH metabolites. RESULTS: All PAH metabolites had a detection rate greater than 60% (67.21%-90.57%) except for 4-OH-PHE at 55.54%. The median concentrations were 0.02-0.11 µg/g Cre except for 1-OH-NAP, 2-OH-NAP, 2-OH-FLU and 9-OH-FLU (0.36-0.50 µg/g Cre). The cluster analysis identified the phenanthrene and fluorene metabolite clusters (containing no other metabolites), while naphthalene metabolites (1-OH-NAP, 2-OH-NAP) could not be clustered without other metabolites. GLM analysis identified that pregnant women with the following characteristics have high urinary concentration of PAH metabolites: overweight, in the last trimester of pregnancy, distance between their house and main traffic lines as <5 m, use fuel for cooking, passive smoking, renovated their residence for less than 3 years, middle family income and office workers. CONCLUSION: The results clarified pregnant women from the economically underdeveloped area could be the victims of PAHs. In addition, PAHs present a demographic and seasonal differential distribution, which will aid in the development of targeted interventions and reduce exposure to PAHs during pregnancy.

Adjuvant radiotherapy in central hepatocellular carcinoma after narrow-margin hepatectomy: A 10-year real-world evidence.

OBJECTIVE: A prospective randomized control study investigated the feasibility and efficacy of adjuvant radiotherapy on patients with central hepatocellular carcinoma (HCC) after narrow-margin hepatectomy (<1 cm). This study presents an updated 10-year real-world evidence to further characterize the role of adjuvant radiotherapy. METHODS: Patients with central HCC after narrow-margin hepatectomy (<1 cm) were prospectively assigned to adjuvant radiotherapy group and control group. Patients' outcome, adverse events, long-term recurrence and survival rates were investigated. RESULTS: The 1-, 5-, and 10-year recurrence-free survival (RFS) rates were 81.0%, 43.9%, and 38.7%, respectively in adjuvant radiotherapy group and 71.7%, 35.8%, and 24.2%, respectively in control group (log-rank test, P=0.09). The 1-, 5-, and 10-year overall survival (OS) rates were 96.6%, 54.7%, and 42.8%, respectively in adjuvant radiotherapy group and 90.2%, 55.1%, and 30.0%, respectively in control group (log-rank test, P=0.20). The 1-, 5-, and 10-year RFS rates for patients with small HCC (≤5 cm) were 91.1%, 51.6%, and 48.4%, respectively in adjuvant radiotherapy group and 80.0%, 36.6%, and 26.6%, respectively in control group (log-rank test, P=0.03). Landmark analysis demonstrated that patients with small HCC in adjuvant radiotherapy group had a significantly improved OS in second five years after treatment in comparison to patients in control group (log-rank test, P=0.05). CONCLUSIONS: Our updated results showed a sustained clinical benefit on reducing recurrence, improving long-term survival for small central HCC by adjuvant radiotherapy after narrow-margin hepatectomy. Long-term survival data also indicated that hepatectomy is an optimal treatment for selected patients with central HCC.

[Analysis of prognostic factors in patients with hepatocellular carcinoma (≤5 cm) underwent hepatectomy].

OBJECTIVE: To explore the clinical and pathological factors influencing the prognosis of patients with hepatocellular carcinoma (HCC)(≤5 cm) after hepatectomy. METHODS: Two hundreds and nineteen cases with HCC(≤5 cm) undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 and July 2013 were collected. The alpha fetoprotein (AFP) level, tumor number, tumor size (diameter), liver cirrhosis, vascular invasion, capsular invasion, differentiation, surgical methods, resection margin, the way of treatments, the situation of recurrence and time to recurrence were analyzed. Log-rank test and the stepwise Cox proportional-hazards models were used to compare the prognosis, respectively. RESULTS: The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3% respectively in all patients.Single factor analysis indicated that vascular invasion, capsular invasion, tumor size, hepatic vascular occult, liver cirrhosis, tumor differentiation, AFP, the way of treatments, the situation of recurrence and time to recurrence can affect the prognosis significantly (all P<0.05). The multifactor analysis showed that AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence were independent prognostic factors (all P<0.05). CONCLUSION: The prognosis of patients with HCC(≤5 cm) underwent hepatectomy are affected by multi-factors, such as AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence.

[Effect of resection margin and tumor number on survival of patients with small liver cancer].

OBJECTIVE: To explore the significance of resection margin and tumor number on survival of patients with small liver cancer after hepatectomy. METHODS: We collected 219 cases with small liver cancer undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 to July 2013. The survival rates were compared by log-rank test between two resection margin groups (≥ 1 cm vs. <1 cm), different tumor number groups (single tumor vs. multiple tumors). We also performed a multifactor analysis by Cox model. RESULTS: The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3%, respectively, in all patients. The median survival time was 28 months in the group of <1 cm resection margin and 36 months in the group of ≥ 1 cm resection margin (P=0.249). The median survival time was 36 months in the group of single tumor and 26 months in the group of multiple tumors (P=0.448). The multifactor analysis also did not show significant effect of resection margin and tumor number on the patients' survival. CONCLUSIONS: For small liver cancer, the resection margin of 1 cm might be advised. Increasing resection margin in further could probably not improve therapeutic effect. Standardized operation and combined treatment will decrease the negative influence of multiple tumors on overall survival.

[Effect of preoperative transcatheter arterial chemoembolization on the perioperative outcome of patients with hepatocellular carcinoma].

OBJECTIVE: To explore the surgical risk, perioperative outcome and the response of patients with hepatocellular carcinoma (HCC) after preoperative transcatheter arterial chemoembolization (TACE). METHODS: A retrospective case-matched study was conducted to compare the characteristics and corresponding measures of patients in the preoperative TACE group and the control group without TACE. A total of 105 patients (82 patients with selective and dynamic region-specific vascular occlusion to perform hepatectomy for patients with complex hepatocellular carcinoma) was included in this study, in which 35 patients underwent TACE therapy, and a 1:2 matched control group of 70 subjects. RESULTS: The patients of preoperative TACE therapy group had a higher level of γ-glutamyl transpeptidase before operation (119.52±98.83) U/L vs. (67.39±61.25) U/L (P=0.040). The operation time was longer in the TACE group than that in the control group but with a non-significant difference (232.60±95.43) min vs. (218.70±75.13) min (P=0.052). The postoperative recovery of liver function and severe complications in the preoperative TACE group were similar to that in the control group (P>0.05). There were no massive hemorrhage, biliary fistula and 30-d death neither in the treatment group and matched control group. CONCLUSIONS: Preoperative TACE therapy has certain negative effect on liver function. It is preferable to use selective and dynamic region-specific vascular occlusion technique during hepatectomy and combine with reasonable perioperative treatment for this group of patients, that can ensure safety of patients and promote their rapid recovery.

[Initial comparison of regional ischemic preconditioning and hemi-hepatic vascular inflow occlusion in resection of hepatocellular carcinoma].

OBJECTIVE: To evaluate preliminarily the clinical efficacy of two types of hepatic inflow occlusion in hepatectomy for hepatocellular carcinoma (HCC). METHODS: A total of 54 patients with HCC who underwent hepatectomy were divided into two groups: RIP group (regional ischemic preconditioning with continuous clamping, n=15) and HHV group (hemi-hepatic vascular inflow occlusion, n=39). HHV was performed by placing a clamp on the right hepatic artery and right portal vein, and was maintained until the liver resection was completed. In the RIP group, HHV was preceded by a 5-min period of ischemia followed by 5 min of reperfusion. The clinical indicators of the two groups were compared. RESULTS: The volume of intraoperative blood loss had significant difference between the two groups (P=0.039). One case (6.7%) in the RIP group and 17 cases (43.6%) in the HHV group received postoperative blood transfusion, showing a significant difference (P=0.010). No postoperative 30-day mortality happened in all patients. No significant differences were found between the two groups in hospital stay or postoperative morbidity, including hepatic insufficiency, infection, ascites, pleural effusion, cardiopulmonary complications and intestinal ventilation time (P>0.05 for all).The RIP group had a significantly higher PTA level at postoperative days 3 and 5 (P<0.001). Although no significant differences were found between the two groups regarding total bilirubin, albumin, prealbumin and aminotransferase (P>0.05) during any postoperative stage, the ALT recovered to normal level in 5 patients (33.3%) of the RIP group and only in one case (2.7%) of the HHV group, with a significant difference between the two groups (P=0.006). CONCLUSION: The results of this study indicate that regional ischemic preconditioning may have better hemostatic effect on hepatectomy, can reduce postoperative blood transfusion and promote early recovery of liver function than hemi-hepatic vascular inflow occlusion.

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers.

INTRODUCTION: Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients. METHODS: All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed. RESULTS: HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months. CONCLUSION: Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.

[Analysis of risk factors of recurrence of hepatocellular carcinoma after control of surgical-risk-factors].

OBJECTIVE: R0 resection, Pringle maneuver, intraoperative massive blood loss and perioperative blood transfusion have been definitely recognized to be surgery-related risk factors of recurrence of hepatocellular carcinoma (HCC) in recent years. The aim of this study was to investigate the post-operative risk factors of recurrence of HCC after control of the above mentioned risk factors. METHODS: 288 consecutive HCC patients underwent hepatectomy with selective regional vascular occlusion by the same surgical team. All patients had R0 resection, less than 800 ml blood loss and had no perioperative blood transfusion. The clinical and pathological factors were retrospectively analyzed. RESULTS: The total 1-year, 3-year and 5-year disease-free survival rate (DFS) was 74.9%, 49.3% and 34.3%, respectively. Univariate analysis showed that serum gamma-glutamyl-transferase rise >55 U/L, AFP > 400 ng/ml, tumor diameter >5 cm, multi-focal lesions, satellite nodules, poor differentiation, microvascular invasion, envelope invasion, postoperative liver insufficiency, preoperative TACE and postoperative TACE were significantly associated with poor DFS. Multivariate Cox analyses revealed that tumor size, satellite nodules, poor differentiation, microvascular invasion and postoperative liver insufficiency were independent prognostic predictors associated with shorter DFS. According to the results of multivariate Cox analysis of 158 cases with at least one risk factor selected from the whole group, further analysis demonstrated that perioperative TACE was not significantly associated with the median DFS (P > 0.05 for all). CONCLUSIONS: Selective regional vascular occlusion may effectively control the surgiury-related risk factors of recurrence of HCC. Tumor features are the main affecting factors of DFS. Preoperative or postoperative TACE do not benefit patients who received curative resection.

[Comparison of the prognosis between male and female patients with hepatocellular carcinoma after hepatectomy].

OBJECTIVE: Hepatocellular carcinoma (HCC) is sexually dimorphic, with a significantly higher incidence in male. But it is not clear whether the women have a better prognosis than the men. The present study aimed to compare the short and long-term outcomes, postoperative recurrence and survival in female and male patients with HCC after hepatectomy. METHODS: Clinicopathological data of retrospective analysis was performed on 40 female and matched 40 male HCC patients treated by hepatectomy in Cancer Hospital of Chinese Academy of Medical Sciences between May 2006 and May 2012 were retrospectively reviewed in this study. Patients were paired in terms of age, chronic hepatitis, Child-Pugh class, tumor size, histological differentiation, presence of satellite nodules and resection margin. RESULTS: Hepatectomy was successfully performed in all 80 cases. There was no significant difference in intraoperative variables and postoperative outcomes between the female and male groups except the level of total bilirubin. The 1-, 3- and 5-year recurrence-free survival rates were 76.7%, 47.4% and 29.7% in the female group and 63.8%, 30.0% and 25.0% in the male group (P = 0.12). Corresponding overall survival rates were 92.2%, 81.5% and 55.4% in the female group and 97.4%, 55.2% and 39.0% in the male group (P = 0.04). CONCLUSION: Certain gender differences might exist in HCC patients after hepatecomy, favoring females in the overall survival and the tolerance for liver injury.

Association of urinary polycyclic aromatic hydrocarbon metabolites with gestational diabetes mellitus and gestational hypertension among pregnant women in Southwest China: A cross-sectional study.

The association of polycyclic aromatic hydrocarbons (PAHs) with gestational diabetes mellitus (GDM) and gestational hypertension during pregnancy has not yet been established. To investigate the association between PAH exposure and GDM and gestational hypertension, we conducted a cross-sectional study of 4206 pregnant women from the Zunyi birth cohort in southwestern China. Gas chromatography/mass spectrometry was used to detect the urinary levels of 10 monohydroxylated PAHs (OH-PAHs). GDM and gestational hypertension were diagnosed and the relevant information was documented by specialist obstetricians and gynecologists. Logistic regression and restricted cubic spline regression were employed to investigate their single and nonlinear associations. Stratified analyses of pregnancy and body mass index data were conducted to determine their moderating effects on the abovementioned associations. Compared with the first quartile of urinary ∑OH-PAHs, the third or fourth quartile in all study participants was associated with an increased risk of GDM (quartile 3: odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.03-1.77) and gestational hypertension (quartile 3: OR = 1.88, 95% CI: 1.26-2.81; quartile 4: OR = 1.58, 95% CI: 1.04-2.39), respectively. Nonlinear associations of 1-OH-PYR with GDM (cutoff level: 0.02 µg/g creatinine [Cr]) and 1-OH-PHE with gestational hypertension (cutoff level: 0.06 µg/g Cr) were also observed. In pregnant women with overweight or obesity, 1-OH-PHE and 3-OH-PHE were more strongly associated with gestational hypertension. Our results indicate that exposure to PAH during pregnancy may significantly increase the maternal risks of GDM and gestational hypertension; however, this finding still needs to be confirmed through larger-scale prospective studies and biological evidence.

DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation.

The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.

[Comparative study of three types of anatomical vascular occlusion method in hepatectomy for liver neoplasms].

OBJECTIVE: To assess the clinical efficacies of three types of anatomical hepatic inflow occlusion method in hepatectomy for liver neoplasms. METHODS: A non-randomized concurrent controlled trial was performed from January 2011 to October 2012, a total of 180 consecutive patients with liver neoplasms underwent hepatectomy similarly. They were divided into 3 groups according to the hepatic inflow occlusion methods during resection: HHV group (hemi-hepatic vascular inflow occlusion, n = 60), MPV group (main portal vein inflow occlusion, n = 60) and HPP group (hemi-portal vein preserved inflow occlusion, n = 60). The primary endpoints were intraoperative blood loss and transfusion requirement while the secondary outcomes were assessed with operating duration, postoperative morbidity, hospital stay, gastrointestinal function and postoperative liver injury. RESULTS: No significant differences existed among three groups in demographic and tumor characteristics and operation-related background (P > 0.05). No mortality happened in 30 days postoperatively in all patients. Intraoperative volume of blood loss had no significant differences among three groups (P = 0.272). Among the patients requiring transfusion, HPP group had the least transfusion requirement (HHV group: (5.00 ± 1.51) U, MPV group:(3.50 ± 1.41) U, HPP group: (2.50 ± 0.93) U, P = 0.004). MPV group showed a significant shorter operating duration (HHV group: (227 ± 59) min, MPV group:(198 ± 56) min, HPP group:(221 ± 79) min, P = 0.042). No significant differences were found among three groups in hospital stay (P = 0.673) or postoperative morbidity (P = 0.735), including hepatic insufficiency, infection and ascites. HHV group showed an earlier recovery of gastrointestinal function (HHV group: (60 ± 12) h, MPV group:(69 ± 9) h, HPP group:(64 ± 8) h, P = 0.000).MPV group had a significantly lower level of aminotransferase at Day 1 and 3 postoperation (d1 ALT: HHV group: (403 ± 271) U/L, MPV group:(304 ± 211) U/L, HPP group: (448 ± 396) U/L, P = 0.033; d1 AST: HHV group: (394 ± 271) U/L, MPV group:(278 ± 189) U/L, HPP group: (432 ± 405) U/L, P = 0.017; d3 ALT: HHV group: (309 ± 193) U/L, MPV group:(232 ± 161) U/L, HPP group:(325 ± 277) U/L, P = 0.048; d3 AST: HHV group:(136 ± 105) U/L, MPV group:(91 ± 73) U/L, HPP group:(120 ± 87) U/L, P = 0.024).But no significant differences were found among three groups regarding total bilirubin, albumin, prealbumin and prothrombin time activity (P < 0.05) during any postoperative stage. CONCLUSION: All three types of anatomical vascular occlusion method are both safe and efficacious in hepatectomy. But no single method has absolute advantage over the other two. HPP method has the best hemostatic effect, MPV offers better postoperative liver function and HHV promotes early recovery of gastrointestinal function.

Comprehensive Analysis of Epigenetic Associated Genes with Differential Gene Expression and Prognosis in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is the most common malignancy of the human digestive system and represents the second leading cause of cancer-related deaths. As early GC is generally mild or asymptomatic and advanced GC is commonly diagnosed, early detection has a significant impact on clinical outcomes. This study aimed to identify epigenetic factors (EFs) as potential GC biomarkers. METHODS: We identified 3572 differential expressed genes (DEGs) from 436 GC tissues and 41 non-tumor adjacent samples through The Cancer Genome Atlas (TCGA) datasets. Among them, a total of 57 overlapped genes were identified as differentially expressed EFs (DE-EFs), including 25 up-regulated DE-EFs and 32 down-regulated DE-EFs. RESULTS: Then, Gene Ontology (GO) enrichment analysis revealed that the DE-EFs were mainly associated with histone modification, chromatin remodeling, histone binding, modificationdependent protein binding, etc. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results suggested that RNA degradation, thermogenesis, shigellosis, insulin resistance, AMPK, and FoxO signaling pathways play roles in the progression of GC. Subsequently, Cox regression and Kaplan-Meier analysis showed that higher expression levels of the three hub EFs, including BRCC3, USP12, and WAC, were associated with better patients' OS. We also found that GC patients in the TCGA dataset with the earlier stage of TNM stage, invasion, depth of tumor, lymph node metastasis, distant metastasis, and younger age had significantly better GC patients' OS. DISCUSSION: Furthermore, as the pathway enrichment analysis showed that BRCC3 participated in NOD-like receptors (NLRs)-mediated signaling and the homologous recombination (HR) pathways, strong and statistically significant positive relationships were found between BRCC3 with genes in NLRs signaling and HR pathways, including BRCA1, BRCA2, Rad51, BRE, TOPBP1, HSP90AA1, CASP1, NEK7, and SUGT1, respectively. CONCLUSION: We found three hub EFs, namely BRCC3, USP12, and WAC, which were downregulated in GC tissues compared to normal tissues, associated with the overall survival of GC patients and could be used as potential biomarkers to predict prognosis in GC patients. The regulation of hub genes in GC may promote the exploration of the epigenetic mechanisms associated with tumorigenesis and provide potential targets for GC diagnosis and treatment.

The association between genital mycoplasma infection and spontaneous abortion: A systematic review and meta-analysis.

Epidemiological findings on the association between genital mycoplasma infection (GMI) and spontaneous abortion are inconsistent. Therefore, this meta-analysis aims to determine whether mycoplasma infection during pregnancy increases the risk of spontaneous abortion. An electronic database search was conducted using China National Knowledge Infrastructure, Elsevier, PubMed, SinoMed, The Cochrane Library, and Wanfang Database from database establishment to October 2021. Sixteen case-controls and 3 prospective cohorts were included. The meta-analysis showed that GMI was positively associated with spontaneous abortion (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.50, 3.67). Of them, case-control studies showed that the GMI proportion in the spontaneous abortion group was higher than that in the normal group (OR 2.13, 95% CI 1.33, 3.43); the cohort study showed that the spontaneous abortion rate in the GMI group was higher than those in non-infected groups (relative risk 5.17, 95% CI 2.07, 12.95; risk difference 0.18, 95% CI 0.09, 0.27). Each outcome indicator was relatively robust in the sensitivity analysis, and no significant publication bias was found in the funnel plots. Our data support that GMI during pregnancy increases the risk of spontaneous abortion. Thus, the monitoring and timely treatment of GMI before pregnancy of GMI are essential to decrease the risk of spontaneous abortion.

Aging-related increases in serum sex hormone-binding globulin levels in men might be related to increased synthesis.

BACKGROUND: Previous studies have indicated that serum sex hormone-binding globulin (SHBG) levels increase with age; however, the causes remain unknown. The present study aimed to clarify whether the increase in SHBG levels is attributable to aging-related increases in SHBG synthesis. METHODS: We examined and evaluated the association of serum SHBG levels with synthesis-related factors in men aged 18-80 years. Additionally, we examined the serum and liver levels of SHBG, hepatic nuclear factor 4α (HNF-4α), and peroxisome proliferator-activated receptor γ (PPAR-γ) in young, middle-aged, and old Sprague-Dawley rats. RESULTS: The study included 209 men in the young group (median age, 33 ± 10 years), 174 men in the middle-aged group (median age, 53 ± 8 years), and 98 men in the elderly group (median age, 71 ± 8 years). Serum SHBG levels increased with age (P < 0.05), whereas HNF-4α and PPAR-γ levels decreased with age (both P < 0.05). Compared with the findings in the young group, the average decline in HNF-4α levels was 2.61 % and 18.46 % in the middle-aged and elderly groups, respectively; the average decreases in PPAR-γ levels in these groups were 12.86 % and 20.76 %, respectively. The results in rats illustrated that liver SHBG and HNF-4α levels increased with age, whereas PPAR-γ and chicken ovalbumin upstream promoter-transcription factor (COUP-TF) levels decreased with age (all P < 0.05). Serum SHBG levels increased in rats with age, whereas HNF-4α and PPAR-γ levels decreased with age (all P < 0.05). CONCLUSIONS: The aging-related increased liver levels of the SHBG synthesis promoter HNF-4α and decreased levels of the SHBG inhibitory factors PPAR-γ and COUP-TF suggest that the aging-related increases in SHBG levels are associated with increased SHBG synthesis.

Determination of Polycyclic Aromatic Hydrocarbons (PAHs) and Phthalates in Human Placenta by Mixed Hexane/Ether Extraction and Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS).

In this study, we evaluated the extraction effect of three different extractants, namely hexane + ether (v/v = 3:1), acetonitrile and ethyl acetate, on polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs) in placenta detected and analysed by triple quadrupole gas chromatography-mass spectrometry (GC-MS/MS). The results showed that n-hexane + ether (v/v = 3:1) had the highest extraction efficiency. Under the optimal conditions, the limits of detection (LOD) for the 10 PAHs were 0.003-0.0167 µg/L with relative standard deviations (RSD) of 1.4-5.48% and detection rates of 68.19-107.05%, and the correlation coefficients were (R2, 0.9982-0.9999). The LODs for the nine PAEs were 0.0015-3.5714 µg/L and the correlation coefficients were (R2, 0.9982-0.9999). The limits of detection (S/N = 3) for the nine PAHs were 0.0015-0.5714 µg/L with relative standard deviations (RSD) of 3.15-8.37%, and the detection rates were 80.45-112.59% with correlations of (R2, 0.9972-0.9998). The method was applied to the analysis of PAHs and phthalates in placenta samples from pregnant women. The method's accuracy and applicability were demonstrated. In comparison with other methods for the detection of PAEs and PAHs, the method proposed in this paper has a wider linear range, lower minimum detection limit and comparable recovery with good correlation. This paper is dedicated to providing another method for improving the performance of extracting solid tissues.

Effects of exposure to phthalate during early pregnancy on gestational diabetes mellitus: a nested case-control study with propensity score matching.

Owing to the complexity of phthalates (PAEs) components and the diversity of their sources, the health hazards of their metabolites to pregnant women remain unclear. This study aimed to explore the relationship between exposure to PAEs during early pregnancy and gestational diabetes mellitus (GDM) in rural pregnant women. We assessed pregnant women with (n = 338) or without (n = 3082) GDM from the ongoing Zunyi Birth Cohort. Participants' urine samples were collected to measure the levels of 10 metabolites of PAEs. GDM was diagnosed using the 75-g oral glucose tolerance test at 24-28 weeks of gestation. We adopted propensity score matching based on GDM-related factors and pregnant women's backgrounds to establish two groups of 338 patients: those with or without GDM. In the cohort, we included 5734 pregnant women; 519 of them developed GDM, yielding a GDM incidence rate of 9.05%. Urinary concentrations of monooctyl phthalate (MOP), mono-benzyl phthalate (MBzP), mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) during early pregnancy were significantly associated with GDM (P < 0.05). Logistic regression models revealed that MEOHP in the urine was positively associated with GDM (odds ratio [OR] = 1.55; 95% confidence interval [CI]: 1.00-2.39). Furthermore, restricted cubic spline models revealed that urine MEOHP concentrations greater than 15.6 µg/L were positively associated with GDM, and approximately 23.5% pregnant women had urine MEOHP concentrations greater than 15.6 µg/L. Thus, approximately 23.5% of pregnant women were at the risk of developing GDM due to MEOHP, which suggested that pregnant women should reduce the use of packaged food and cosmetics to reduce the risk of GDM. However, further molecular biology experiments are required to confirm these findings and to elucidate the underlying mechanisms.

Maternal urine phthalate metabolite exposure and miscarriage risk: a nested case-control study of the Zunyi Birth Cohort.

Phthalates (PAEs) are widespread persistent organic pollutants and endocrine disruptors. However, the associations between PAE exposure and the risk of miscarriage in humans are unclear, and an insufficient number of studies have evaluated the possible threshold or dose-dependent effects of first trimester PAE exposure on miscarriage risk. Our research measured the levels of mono-methyl phthalate (MMP), mono-ethyl phthalate, mono-isobutyl phthalate, MiBP mono-butyl phthalate (MBP), mono-octyl phthalate, mono-benzyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in maternal urine collected in early gestation between 150 pregnancies ending in miscarriage and 150 pregnancies with live birth. We also estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PAE as a continuous variable or quartile. A restrictive cubic splines was used to assess dose-dependent effects after controlling for maternal characteristics (e.g., age, educational level). we identified monotonically increasing dose-dependent effects of MEHHP and MMP on the risk of miscarriage. The largest effect estimates were approximately threefold higher for the highest MBP (OR = 2.57; 95% CI = 1.32-5.01) or MMP quartile (OR = 3.57; 95% CI = 1.82-7.00) and two-fold higher for the highest MEHHP quartile (OR = 2.12; 95% CI = 1.10-4.11). Our research preliminarily obtained possible thresholds of MBP, MEHHP, and MMP which were 18.07, 2.38, and 0.80 µg/g Cr for the risk of miscarriage, respectively. First-trimester exposure to MBP, MEHHP, and MMP exceeding certain thresholds increases the risk of miscarriage.