Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus. It leads to distressing and expensive clinical sequelae such as foot ulceration, leg amputation, and neuropathic pain (painful-DPN). Unfortunately, DPN is often diagnosed late when irreversible nerve injury has occurred and its first presentation may be with a diabetic foot ulcer. Several novel diagnostic techniques are available which may supplement clinical assessment and aid the early detection of DPN. Moreover, treatments for DPN and painful-DPN are limited. Only tight glucose control in type 1 diabetes has robust evidence in reducing the risk of developing DPN. However, neither glucose control nor pathogenetic treatments are effective in painful-DPN and symptomatic treatments are often inadequate. It has recently been hypothesized that using various patient characteristics it may be possible to stratify individuals and assign them targeted therapies to produce better pain relief. We review the diagnostic techniques which may aid the early detection of DPN in the clinical and research environment, and recent advances in precision medicine techniques for the treatment of painful-DPN.

Peroral endoscopic myotomy (POEM) has been widely applied to the treatment of achalasia. The aim of this study is to retrospectively investigate the long-term outcome of POEM in patients with achalasia. Patients undergoing POEM at our center with a minimum follow-up of 3 years were enrolled in this study. Relief of patients' symptom was defined as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, symptoms relapse, and clinical reflux adverse events. The Chi-square test was performed to determine the potential predictors of surgical failure. Sixty-seven patients (aged 40.7 ± 15.3 years) were recruited in the study, with a mean follow-up period of 40.1 ± 2.8 months. At the final follow-up, the median Eckardt score reduced from 7.6 ± 2.3 preoperatively to 1.9 ± 1.7 (P < 0.001), the lower esophageal sphincter pressure was reduced from 35.4 ± 13.7 mmHg preoperatively to 8.9 ± 4.1 mmHg (P < 0.001), and the height of the barium column at 5 min after barium swallowed was reduced from 9.7 ± 1.6 cm preoperatively to 2.9 ± 2.1 cm (P < 0.001). Eight patients had symptoms relapse and nine patients developed reflux esophagitis. Type III achalasia was found to be indicative of surgical failure. POEM was a promising treatment for patients with achalasia, which can yield a long-term relief of the symptom and a low rate of clinical reflux adverse events.

Introduction: Metastasis and drug resistance contribute substantially to the poor prognosis of colorectal cancer (CRC) patients. However, the epigenetic regulatory mechanisms by which CRC develops metastatic and drug-resistant characteristics remain unclear. This study aimed to investigate the role of miR-302a in the metastasis and molecular-targeted drug resistance of CRC and elucidate the underlying molecular mechanisms.Methods: miR-302a expression in CRC cell lines and patient tissue microarrays was analyzed by qPCR and fluorescence in situ hybridization. The roles of miR-302a in metastasis and cetuximab (CTX) resistance were evaluated both in vitro and in vivo. Bioinformatic prediction algorithms and luciferase reporter assays were performed to identify the miR-302a binding regions in the NFIB and CD44 3'-UTRs. A chromatin immunoprecipitation assay was performed to examine NFIB occupancy in the ITGA6 promoter region. Immunoblotting was performed to identify the EGFR-mediated pathways altered by miR-302a.Results: miR-302a expression was frequently reduced in CRC cells and tissues, especially in CTX-resistant cells and patient-derived xenografts. The decreased miR-302a levels correlated with poor overall CRC patient survival. miR-302a overexpression inhibited metastasis and restored CTX responsiveness in CRC cells, whereas miR-302a silencing exerted the opposite effects. NFIB and CD44 were identified as novel targets of miR-302a. miR-302a inhibited the metastasis-promoting effect of NFIB that physiologically activates ITGA6 transcription. miR-302a restored CTX responsiveness by suppressing CD44-induced cancer stem cell-like properties and EGFR-mediated MAPK and AKT signaling. These results are consistent with clinical observations indicating that miR-302a expression is inversely correlated with the expression of its targets in CRC specimens.Conclusions: Our findings show that miR-302a acts as a multifaceted regulator of CRC metastasis and CTX resistance by targeting NFIB and CD44, respectively. Our study implicates miR-302a as a candidate prognostic predictor and a therapeutic agent in CRC.

Background Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH. Results Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO. Conclusion Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels.

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BackgroundThis study assessed the health related quality of life of family caregivers (FCs) of leukemia patients by using the health utility scores derived from the EuroQol five-dimensional (EQ-5D) questionnaire.MethodsA cross-sectional survey was undertaken on 306 family caregivers of leukemia patients to assess their health utility using the EQ-5D-3L. Participants were recruited from three hospitals in China’s Heilongjiang province. The health utility scores of the participants were estimated based on the Chinese EQ-5D-3L value set and compared with those of the local general population. Factors predicting the health utility scores were identified through the Kruskal-Wallis analysis of variance and median regression analyses.ResultsFCs had lower health utility scores than the general population (p < 0.001). The participants with a lower socioeconomic status had lower utility scores and reported more problems than those with a higher socio-economic status. Better family function and higher social support were associated with higher health utility scores. The type of leukemia, household income, and social support are significant predictors of health utility scores of the FCs. Chronic lymphocytic leukemia, low socio-economic status, and low social support are associated with lower health utility scores of the FCs.ConclusionsFCs for leukemia patients have lower health utility scores than the local general population, as measured by the EQ-5D-3L. There is an immediate need to address the health concerns of FCs, who play an important role in the Chinese health care system.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4855-y) contains supplementary material, which is available to authorized users.

Objective: Hypertension is one of the most common public health issues worldwide. However, few existing studies examining health-related quality of life (HRQoL) were conducted on elderly patients with hypertension in China. Hence, this study aimed to assess the HRQoL of elderly patients with hypertension and its influencing factors using EuroQol five-dimensional-three-level (EQ-5D-3L) in China.Methods: Data were obtained from the 6th National Health Service Survey in Heilongjiang province from June to July 2018, with a stratified multistage random cluster sampling method. All eligible participants were interviewed using a standardized questionnaire, which included the EQ-5D-3L, socio-demographics characteristics, clinical and lifestyle characteristics. The mean EQ-5D index scores for the different subgroups were evaluated using ANOVA. A Tobit regression model was also employed to analyze the potential factors influencing HRQoL.Results: A total of 705 elderly patients with hypertension were included in this study. The mean EQ-5D utility score was 0.79 [standard deviation (SD) = 0.23]. The proportion of participants reporting pain/discomfort problems was the highest (57.0%), while problems in self-care was the lowest (17.2%). Influencing factors of HRQoL for elderly patients with hypertension included gender, age, income, education level, physical activity, health examination and coexisting diseases. Specifically, the female gender, being above 80 years old, having a lower education and/or higher income, and the presence of coexisting diseases were associated with lower utility index. In contrast, regular physical activity and medical examination had a positive impact on the HRQoL of elderly hypertension patients.Conclusion: Overall, elderly patients with hypertension in China have a lower HRQoL than the general population. To improve the HRQoL of elderly patients with hypertension, it is imperative that better public health education is provided to enhance the knowledge of hypertension, encourage the adoption of healthy habits such as regular physical activity and medical examination, and improve the management of coexisting diseases. More care should also be directed to males with hypertension who are above 80 years old.

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