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BackgroundMiRNAs play important roles in regulating many fundamental biological processes. Deregulation of miRNAs is involved in the initiation and progression of cancer. MiR-193b is regarded as tumor suppressor in many types of cancers. However, the role of miR-193b in ovarian cancer is poorly understood.Material/MethodsThe expression level of miR-193b in ovarian cancer cell lines and ovarian cancer samples was evaluated using quantitative real-time reverse transcription-PCR (qRT-PCR). The ovarian cancer patients were categorized into a high miR-193b expression group and a low miR-193b expression group according to the median miR-193b expression level. The correlation between tissue miR-193b expression and the patients’ clinicopathological factors, as well as survival, was also analyzed.ResultsThe results showed that the miR-193b expression was significantly down-regulated in ovarian cancer cell lines and tumor tissues compared with normal controls. In addition, tissue miR-193b expression was positively correlated with FIGO stage (P=0.001), histological grade (P=0.032), ascites (P=0.019), lymph node metastasis (P=0.003), and tumor size (P=0.041). Among 116 patients with ovarian cancer examined, the 5-year overall survival (OS) rates were 62.5% and 22.01% in patients with high and low miR-193b expression, respectively (P=0.003). Multivariate analysis showed that tissue miR-193b is an independent prognostic factor in patients with ovarian cancer (HR=4.219; P=0.015).ConclusionsReduction of miR-193b was found in ovarian cancer and its lower expression was associated with poorer prognosis. Tissue miR-193b showed potential as novel biomarker for ovarian cancer.

Supplemental Digital Content is Available in the Text. The prevalence of pain among nursing home residents who are not receiving analgesics or adjuvants suggests a need to improve pain diagnosis and management procedures.

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

Background Gabapentinoids have been prescribed off-label for almost all types of pain. The geographic variation in the use of gabapentinoids as analgesics remains unknown. Objective To describe the geographic variation in gabapentinoids, opioids and concurrent use of both for pain by US state and metropolitan statistical area (MSA). Methods We conducted a cross-sectional study on December 1, 2018, among commercially insured adults aged 18–64 years without epilepsy or opioid use disorders using IBM ® MarketScan ® Research Databases. We described the geographic variation in the analgesic regimens (gabapentinoids, opioids and concurrent use of both) by state and MSA, and assessed factors associated with the geographic variation using multilevel logistic regression. Results We included 9,314,197 beneficiaries; 1.4% had gabapentinoids, 1.5% had opioids and 0.3% had concurrent use of both. The majority of gabapentinoid use lacked an FDA-approved indication. Use of the analgesic regimens varied across states (gabapentinoids (median (interquartile range)): 1.4% (1.2–1.7%); opioids: 1.5% (1.2–1.9%); both: 0.3% (0.2–0.4%)) and MSAs (gabapentinoids: 1.6% (1.3–2.0%); opioids: 1.8% (1.3–2.3%); both: 0.3% (0.2–0.5%)). Demographics explained the largest proportion of the between-state and between-MSA variation. The pattern of the geographic variation in gabapentinoids was similar to that of opioids across states and MSAs. Conclusion Gabapentinoids were as commonly used as opioids for pain in a commercially insured population (mostly off-label). The geographic variation in gabapentinoids was similar to that of opioids, which suggests that gabapentinoids may be widely used as alternatives or adjuvants to opioids across the US.

Background Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC. Methods In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled. Eligible patients received oral apatinib 500 mg on day 1 to 21, plus oral etoposide 50 mg on day 1 to 14 of a 3-week cycle until disease progression or intolerable toxicities. Etoposide was administered up to six cycles. The primary endpoint was progression-free survival (PFS). Results From September 2018 to September 2021, 40 patients with advanced TNBC were enrolled. All patients received previous chemotherapy in the advanced setting, with the median previous lines of 2 (1–5). At the cut-off date on January 10, 2022, the median follow-up was 26.8 (1.6–52.0) months. The median PFS was 6.0 (95% confidence interval [CI]: 3.8–8.2) months, and the median overall survival was 24.5 (95%CI: 10.2–38.8) months. The objective response rate and disease control rate was 10.0% and 62.5%, respectively. The most common adverse events (AEs) were hypertension (65.0%), nausea (47.5%) and vomiting (42.5%). Four patients developed grade 3 AE, including two with hypertension and two with proteinuria. Conclusions Apatinib combined with oral etoposide was feasible in pretreated advanced TNBC, and was easy to administer. Clinical trial registration Chictr.org.cn, (registration number: ChiCTR1800018497, registration date: 20/09/2018)

Ovarian cancer is the eighth most common malignancy among women worldwide. Ovarian cancer exhibits no obvious symptoms in the early stage of tumorigenesis and currently, no effective methods for the early detection and treatment of ovarian cancer have been established. Therefore, the identification of novel targets is critical to the early diagnosis and clinical treatment of ovarian cancer. microRNAs (miRs) are small non-coding RNAs, which serve an important biological role in a number of physiological processes and in oncogenesis. Previous studies have reported that miRNA-193b is dysregulated in a variety of types of human cancer. However, the roles of miRNA-193b in human ovarian cancer has not been determined. The present study investigated the roles of miRNA-193b in human ovarian cancer cells. Reverse transcription-quantitative PCR results indicated that the expression of miRNA-193b in ovarian cancer cells was significantly down-regulated compared with non-malignant cells. Cell counting kit-8 results indicated that the up-regulation of miRNA-193b inhibited ovarian cancer cell proliferation and induced ovarian cancer cell apoptosis. The present study also indicated that stathmin 1 (STMN1) was a direct target of miRNA-193b, and the up-regulation of miRNA-193b significantly decreased the expression of STMN1 in ovarian cancer cells. In conclusion, the results demonstrated that miRNA-193b serves as a tumor suppressor in human ovarian cancer by inhibiting cell proliferation and inducing cell apoptosis. Therefore, the assessment of miRNA-193b may provide insight into a novel diagnostic biomarker and potential therapeutic target for patients with ovarian cancer.

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