Background and Purpose: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP.Experimental Approach: A streptozotocin‐induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate astrocyte activity. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety‐like behaviours were detected using open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA.Key Results: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and pain‐related negative emotions in DNP rats. In contrast, temporary activation of BLA astrocytes induced allodynia without anxious behaviours in naive rats. In addition, koumine (KM) alleviated mechanical allodynia and anxiety‐like behaviours in DNP rats, inhibited the activation of BLA astrocytes and suppressed the inflammatory response. Furthermore, persistent activation of BLA astrocytes through chemogenetics mimicked chronic pain, and KM alleviated the pain hypersensitivity and anxiety‐like behaviours.Conclusion and Implications: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocyte activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. KM ameliorates DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.

Objective: This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. Methods: A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. Results: Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I–IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I–IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I–IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I–IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). Conclusion: Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs.

Gene polymorphisms had been found to be associated with increased risk of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to assess the association between rs2896019 and rs3810622 in PNPLA3 with the susceptibility to NAFLD in Han Chinese population. A total of 384 NAFLD patients and 384 controls were enrolled in the study. Blood samples collected from each subject were used for biochemical index analysis and DNA extraction. Genotyping analyses of PNPLA3 rs2896019 and rs3810622 were performed by real-time PCR methods. Results showed that patients with genotype GG of rs2896019 had a higher incidence of NAFLD than patients with genotypes GT and TT (62.4% vs 52.0% and 43.3%, respectively, P = 0.002), and a higher risk of moderate to severe NAFLD than patients with genotypes GT and TT (60.3% vs 46.2% and 40.2%, respectively, P = 0.03). Furthermore, patients with genotype GG of rs2896019 had higher levels of low-density lipoprotein (LDL, P < 0.001), ALT (P = 0.003), and AST (P = 0.002). Patients with genotype TT of rs3810622 had a higher incidence of NAFLD than patients with genotypes CT and CC (56.7% vs 48.4% and 41.5%, respectively, P = 0.013). Likewise, patients with genotype TT of rs3810622 had higher levels of ALT (P = 0.021) and blood glucose (GLU) (P = 0.034). Haplotype association analysis showed that GT haplotype conferred a statistically significant increased risk for NAFLD (OR = 1.49; 95% CI = 1.20–1.84, P < 0.01). These results suggest that PNPLA3 rs2896019 and rs3810622 polymorphisms significantly contribute to increased NAFLD risk in Han Chinese population.

Purpose: To present a nomogram to predict overall survival in patients with FIGO-2018 II to III squamous cell cervical carcinoma undergoing radical radiotherapy. Patients and Methods: Patients diagnosed with FIGO-2018 II to III squamous cell cervical cancer between December 2013 and December 2014 were analyzed retrospectively. The optimal cutoff point for tumor length and width were determined by R package. We identified prognostic factors by univariate and multivariate Cox proportional-hazard regression, then built a nomogram to visualize the prediction model. Our model was compared to the 2018 FIGO staging prediction model. Harrell’s concordance index, receiver operating characteristic curve, calibration plot were used to evaluate the discriminability and accuracy of the predictive models, and decision curve analysis (DCA) was used to show the net benefits. Results: Data from 469 patients were included in the final analyses. The cutoff values of tumor length and width were 5.10 cm and 4.13 cm, respectively. Four independent prognostic variables—tumor length, tumor width, lower one-third vaginal involvement, and lymph node metastases—were used to establish the nomogram. The C-index of the nomogram was 0.71 (95%, CI = 0.66– 0.77), which was better than that of the 2018 FIGO stage prediction model (C-index: 0.62, 95% CI = 0.58– 0.66, p = 0.009). The calibration plot of the nomogram was a good fit for both 3-year and 5-year overall survival predictions. And DCA curves showed that net benefits for our model were higher than FIGO-2018 staging system. Conclusion: A clinically useful nomogram for calculating overall survival probability in FIGO-2018 II to III squamous cell cervical cancer patients who had received radical radiotherapy was developed. Tumor length, tumor width, lower one-third vaginal involvement, and lymph node metastases were found to be independent prognostic factors. Our model performed better than the 2018 FIGO staging model. The findings could help clinicians in China to predict the survival of these patients in clinical care and research.

Purpose. This study aimed to assess the cost-effectiveness of neoadjuvant therapy in combination with surgery and adjuvant therapy compared with either surgery alone or surgery plus adjuvant therapy for the treatment of neuroendocrine cervical tumors (NETs). Materials and methods. A single-institution retrospective analysis of 107 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. We divided the patients who underwent radical surgery into two groups: neoadjuvant therapy (NACT) and non-neoadjuvant therapy (non-NACT) groups. We performed subgroup analysis of overall survival and cost-effectiveness by dividing the patients with stage I-IV disease into four subgroups. An assessment was constructed to reflect the costs and effectiveness of the treatment from the perspectives of both clinical practice and health economics.Results. The NACT group had -0.45 life-years (LYs) at an incremental cost of $15197.58, compared with the non-NACT group, which means that it is not cost-effective. However, subgroup analysis of patients with stage II disease showed that the NACT group had significantly better overall survival time than the non-NACT group (median overall survival had not been reached versus 29.23 months, p＜0.001). The NACT group had an incremental cost-effectiveness ratio (ICER) of $5921.43/LY compared with the non-NACT group for stage II disease. Probabilistic sensitivity analyses showed that when the willingness-to-pay (WTP) threshold reached $31118.29/LY, which is nearly three times China's per capita GDP 2020, the probability of NACT being cost-effective was 97% versus non-NACT group in the treatment of stage II neuroendocrine tumors of the uterine cervix. Conclusion. NACT is not a cost-effective treatment strategy compared with non-NACT in the treatment of NETs, but may be a cost-effective treatment option for stage II NETs.

Objectives: To develop and externally validate MRI-based radiomics and clinicoradiomics models for predicting pathological lymph node metastasis (LNM) in neuroendocrine carcinoma of the cervix (NECC). Methods: This retrospective two-center study included 133 patients who underwent pretreatment pelvic MRI and pathological nodal assessment: 93 for development and 40 for external validation. Intratumoral and peritumoral features were extracted from T2-weighted, diffusion-weighted, and contrast-enhanced T1-weighted images. Stratified nested fivefold cross-validation evaluated the complete revised selection process. Locked models were assessed for discrimination, calibration, and exploratory net benefit, with conventional MRI nodal assessment as a comparator. Results: Pathological LNM was present in 54/133 patients (40.6%). The selected radiomics-only k-nearest neighbors (KNN) model had an external AUC of 0.783 (95% CI, 0.630 to 0.935), accuracy of 0.800, sensitivity of 0.813, and specificity of 0.792. The complete selection procedure yielded an out-of-fold AUC of 0.731. External AUCs were 0.727 for the clinical/MRI model and 0.767 for the clinicoradiomics model; neither fusion model differed significantly from the clinical/MRI comparator. Conventional MRI sensitivity was 0.563, with no significant paired difference from the selected model (p = 0.125). External calibration was imperfect (Brier score, 0.186; slope, 0.672). Conclusions: MRI radiomics showed moderate external discrimination of pathological LNM in NECC. Adding clinical variables did not demonstrate further benefit. Multicenter validation, recalibration, and clinical-impact assessment are needed before clinical application.