Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

The statistical data on Traditional Chinese Medicine (TCM) has not been fully exploited,resulting in the gap between the storage and usage of the TCM statistical data resources. The study on the retrospective collection, arrangement and application of Traditional Chinese Medicine Statistical Data aims to enhance the usage of TCM statistical data, basing on the collection and arrangement of the authoritative TCM statistical data, common analysis of the TCM statistical data from the founding of the People Republic of China.A pilot TCM Statistics Information Database and a TCM Health Statistics Data Query System have been established with the computer database technology, the object-oriented programming tool (C#) and the Internet Browser-based presentation programming tool (ASP. Net), providing the initial functions of the data retrieval and the graphical presentation of the search results on TCM statistics data. This paper explores "statistical data-oriented with attributes description" as the idea to establish the statistical database of complex statistical data, with the solution of the data problems such as numerous of data, diverse of data units, lack of regularity and hard to be classified. The study realizes the building of TCM Statistics Information Database and the retrieval finction of TCM statistical data, which lays a foundation on the building of Traditional Chinese Medicine Industry Statistics Database and the information services of TCM statistics data in the future.

Basing on the introductions to the three levels about the health statistics,including the concept of staffstics,the overview of the health statistics development and the current status of the Health Statistics on Traditional Chinese Medicine,we discuss the significance of Health Statistics on Traditional Chinese Medicine and analysis its existing problems,possible reasons and solutions.

On May 12,2008,a disastrous earthquake scaled 8.0 Richter hit Wenchuan,Sichuan province in China.Treating the acute kidney injury caused by crush syndrome in survivals of the earthquake has been a big challenge to the nephrologists.In this paper,we shared our experiences on the multi-disciplinary collaboration in management of acute kidney injury caused by crush syndrome.In addition to surgical therapy for crush injury and compartment syndrome and the renal replacement therapy for acute renal injury and its related complications,the early multi-disciplinary collaboration including rehabilitation,mental health care,infection control and ICU also contributed greatly to the successful treatment of the victims of the earthquake.