Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.

BACKGROUND: To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). METHODS: Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. RESULTS: We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). CONCLUSION: R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Impact of different postoperative adjuvant therapies on the survival of early-stage cervical cancer patients with one intermediate-risk factor: A multicenter study of 14 years.

OBJECTIVE: To compare survival outcomes of different postoperative adjuvant therapies (PATs) for early-stage cervical cancer (ECC) patients with one intermediate-risk pathological factor (IPF). METHODS: A total of 2889 patients with stage IA1 to IIA2 cervical cancer were included in this study. Three PAT groups were identified, namely a no adjuvant therapy (NAT) group (n = 773), an adjuvant radiotherapy/chemoradiotherapy (ART) group (n = 1648) and an adjuvant chemotherapy (ACT) group (n = 468). Kaplan-Meier analysis and COX regression analysis were used to compare the overall survival (OS) and disease-free survival (DFS) among the three groups, before and after propensity score matching (PSM). RESULTS: The recurrence and mortality rate rates in the NAT, ART and ACT groups were 9.2%, 8.6%, and 7.9%, respectively (p = 0.737). Kaplan-Meier analysis demonstrated no significant differences in the NAT, ART, and ACT groups in 5-year OS rates (92.8% vs. 93.6% vs. 94.7%, p = 0.594) and DFS rates (88.7% vs. 89.6% vs. 90.5%, p = 0.772). Post-hoc tests yielded similar results, with no differences in 5-year OS and DFS (NAT vs. ART, before and after matching, p > 0.05); (NAT vs. ACT, before and after matching, p > 0.05); and (ACT vs. ART, before and after matching, p > 0.05). CONCLUSION: Postoperative adjuvant radiotherapy, chemoradiotherapy, and chemotherapy are not associated with survival outcomes of ECC patients with one IPF. Considering the side effects and impact on patients' quality of life, the PATs should be carefully considered.

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent manner.

Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down-regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet ß-cell function. Importantly, FGF21 knockout exacerbated palmitate-induced islet ß-cell failure and suppression of glucose-stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced ß-cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3-kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21-induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21-induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling-dependent insulin expression and secretion.

CXCL16 deficiency attenuates diabetic nephropathy through decreasing oxidative stress and inflammation.

Soluble C-X-C chemokine ligand 16 (CXCL16) is related to the inflammatory response in liver injury and involved in the pathogenesis of renal dysfunction in diabetes patients. However, the exact role of elevated CXCL16 in diabetic nephropathy (DN) remains unclear. In this study, we investigated the role of CXCL16 in streptozcin (STZ)-induced diabetic nephropathy (DN) in mice. The results showed that fasting blood glucose (FBG) and 24 h urinary protein, triglyceride, and cholesterol levels increased in diabetic mice, and these changes were partially ameliorated in CXCL16 KO mice. Meanwhile, the results also showed that ROS generation was suppressed and the expression levels of inflammatory factors and infiltration factors were inhibited both in vivo and in vitro using DN models. In addition, the total AKT protein and p-AKT levels were decreased in CXCL16-depleted HK-2 cells that were treated with LPS. These findings suggest that the CXCL16 gene product promotes inflammatory factors and cell infiltration factors, and inhibits the expression of antioxidant factors to accelerate the development of DN, and CXCL16 deficiency attenuates DN may be involved in the AKT signaling pathway.

Hepatic CXCL16 is increased in gallstone accompanied with liver injury.

BACKGROUND AND AIMS: This study aimed to investigate the relationship between circulating soluble C-X-C chemokine ligand 16 (CXCL16) levels and clinical characteristics of gallstone. METHODS: 93 subjects including 53 subjects with gallstone, 25 subjects with nonalcoholic fatty liver disease (NAFLD), and 40 control subjects were recruited. All gallstone subjects underwent ultrasounds to confirm the gallstone patients. Serum CXCL16 levels and other clinical and biochemical parameters in all subjects were obtained based on standard clinical examination methods. Liver tissues from patients with gallstone undergoing cholecystotomy and healthy subjects were also used to determine the hepatic CXCL16 profiles by IHC staining and real-time quantitative PCR. RESULTS: Serum CXCL16 levels were significantly increased in patients with gallstone and NAFLD as compared to healthy controls (P < 0·001). Hepatic CXCL16 mRNA and protein levels were also significantly increased in gallstone patients following with elevation of hepatic triglycerides and free fatty acid concentration, as compared to those in healthy subjects (P < 0·001). Otherwise, serum CXCL16 levels positively correlated with nonalcoholic fatty liver disease (NAFLD), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT) and direct bilirubin (P < 0·05), but negatively with total protein and albumin after adjustment with age and gender. Multiple stepwise regression analyses indicated that CXCL16 was independently associated with AST, NAFLD and albumin (P < 0·05, respectively). CONCLUSIONS: Serum CXCL16 levels are significantly increased in patients with gallstone, and are independently associated with liver injury in Chinese population, suggesting that CXCL16 may be a biomarker of liver injury in subjects with gallstone or NAFLD.

CXCL16 deficiency attenuates acetaminophen-induced hepatotoxicity through decreasing hepatic oxidative stress and inflammation in mice.

Chemokine C-X-C ligand 16 (CXCL16), a single-pass Type I membrane protein belonging to the CXC chemokine family, is related to the inflammatory response in liver injury. In present study, we investigated the pathophysiological role of CXCL16, a unique membrane-bound chemokine, in acetaminophen (APAP)-induced hepatotoxicity in mice. Mice were injected with APAP, and blood and tissue samples were harvested at different time points. The serum high-mobility group box 1 and CXCL16 levels were quantified by sandwich immunoassays. The liver tissue sections were stained with hematoxylin-eosin or with dihydroethidium staining. The expressions of CXCL16 and other cytokines were examined by real-time polymerase chain reaction. Ly6-B, p-jun N-terminal kinase (p-JNK), and JNK expressions were measured by western blot analysis. Intracellular glutathione, reactive oxygen species, and malondialdehyde levels were also measured. APAP overdose increased hepatic CXCL16 mRNA and serum CXCL16 protein levels. CXCL16-deficient mice exhibited significantly less liver injury and hepatic necrosis, as well as a lower mortality than wild-type (WT) mice in response to APAP-overdose treatment. APAP elevated the production of oxidative stress and decreased mitochondrial respiratory chain activation in WT mice, which was strongly reversed in CXCL16-knockout mice. In addition, CXCL16 deficiency inhibited the neutrophil infiltration and the production of proinflammatory cytokines triggered by APAP-overdose treatment. Our study revealed that CXCL16 is a critical regulator of liver immune response to APAP-induced hepatotoxicity, thus providing a potential strategy for the treatment of drug-induced acute liver failure by targeting CXCL16.

Genetic diversity analysis and core germplasm bank construction in cold resistant germplasm of rubber trees (Hevea brasiliensis).

The rubber tree, Hevea brasiliensis (Willd. ex Adr. de Juss.) Muell. Arg., is the sole plant worldwide utilized for the commercial production of natural rubber. Following years of breeding, there exists a wide array of germplasm differentiation in rubber trees. The exploration of diversity and population structure within rubber tree germplasm resources, alongside the establishment of core germplasm resources, is instrumental in elucidating the genetic background and facilitating the effective utilization and management of these resources. By employing SNP molecular marker technology, 195 rubber tree resources were amplified, their genetic diversity analyzed, and a fingerprint map was subsequently constructed. Through this process, the cold-resistant core germplasm of rubber trees was identified. The results revealed that the PIC, He, and pi values ranged from 0.0905 to 0.3750, 0.095 to 0.5000, and 0.0953 to 0.5013, respectively. Both group structure analysis and cluster analysis delineated the accessions into two groups, signifying a simple group structure. A core germplasm bank was established with a sampling ratio of 10%, comprising 21 accessions divided into two populations. Population G1 consists of 20 accessions, while population G2 comprises 1 accession. The research findings have led to the creation of a molecular database that is anticipated to contribute to the management and subsequent breeding applications of rubber tree accessions.

Initial treatment for FIGO 2018 stage IIIC cervical cancer based on histological type: A 14-year multicenter study.

BACKGROUND: To compare the oncological outcomes of radical chemotherapy (R-CT), abdominal radical hysterectomy (ARH), and neoadjuvant chemotherapy and radical surgery (NACT) for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer, according to histological types: squamous cell carcinoma (SCC) and adenocarcinoma (AC)/adenosquamous cell carcinoma (ASC). METHODS: A comparison of 5-year overall survival (OS) and disease-free survival (DFS) was performed for the SCC and AC/ASC subgroups for the three initial treatments, assessed using Kaplan-Meier and Cox proportional hazards regression analysis and validated using propensity score matching (PSM). RESULTS: The study included 4086 patients: R-CT, n = 1913; ARH, n = 1529; and NACT, n = 644. AC/ASC had a lower survival rate (63.7%) than SCC (73.6%) and a higher recurrence and mortality rate (36.3% and 26.4%, respectively). The 5-year OS and DFS rates were different in the SCC group for R-CT, ARH, and NACT (OS: 69.8% vs. 80.8% vs. 73.0%, p < 0.001; DFS: 66.7% vs. 70.7% vs. 56.4%, p < 0.001), also in the AC/ASC group (OS: 46.1% vs. 70.6% vs. 55.6%, p < 0.001; DFS: 42.7% vs. 64.6% vs. 40.8%, p < 0.001). As for initial treatment, survival outcomes were worse for AC/ASC treated with R-CT and ARH than for SCC (both p < 0.05), with no group differences between the two treated with NACT. CONCLUSION: Initial treatment influences oncological prognosis for patients with FIGO 2018 stage IIIC cervical cancer. ARH is an alternative treatment for stage IIIC cervical SCC and AC/ASC, and NACT needs to be chosen with caution, moreover, R-CT for AC/ASC requires careful selection.

Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet.

Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin.