Introduction Despite advances in drug research and development, our knowledge of the underlying molecular mechanisms of many diseases remains inadequate. This have led to limited effective medicines for several diseases. To address these challenges, efficient strategies, novel technologies, and policies are urgently needed. The main obstacles in drug discovery and development are the mounting cost, risk, and time frame needed to develop new medicines. Fair pricing and accessibility is another unmet global challenge.Areas covered Here, the authors cover the pace, risks, cost, and challenges facing drug development processes. Additionally, they introduce disease-associated data which demand global attention and propose solutions to overcome these challenges.Expert opinion The massive challenges encountered during drug development urgently call for a serious global rethinking of the way this process is done. A partial solution might be if many consortiums of multi-nations, academic institutions, clinicians, pharma companies, and funding agencies gather at different fronts to crowdsource resources, share knowledge and risks. Such an ecosystem can rapidly generate first-in-class molecules that are safe, effective, and affordable. We think that this article represents a wake-up call for the scientific community to immediately reassess the current drug discovery and development procedures. To evaluate the effect of multimodal exercises integrated with cognitive-behavioural therapy on disability, pain, and quality of life in patients suffering from failed back surgery syndrome (FBSS), and to appraise its extent in the long term. By means of a parallel-group superiority-controlled trial, 150 outpatients were randomly assigned to a 10-week individual-based multimodal programme of task-oriented exercises integrated with cognitive-behavioural therapy (experimental group, 75 patients) or individual-based general physiotherapy (control group, 75 patients). Before treatment, 10 weeks later (post-treatment), and 12 months after the end of treatment, the Oswestry Disability Index (primary outcome), the Tampa Scale for Kinesiophobia, the Pain Catastrophising Scale, a pain intensity numerical rating scale and the Short-Form Health Survey were evaluated. Linear mixed model analysis for repeated measures was carried out for each outcome measure. Significant group (  < 0.001), time (  < 0.001), .Psychologists should explain how to modify useless beliefs and support adequate behaviours, in order to produce constructive attitudes towards perceived disability.Introduction Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular calcium (Ca2+) release channels located on the endoplasmic/sarcoplasmic reticulum. The availability of the structure of the ligand-binding domain of IP3Rs has enabled the design of compatible ligands, but the limiting step remains their actual effectiveness in a biological context.Areas covered This article summarizes the compelling literature on both agonists and antagonists targeting IP3Rs, emphasizing their strengths and limitations. The main challenges toward the discovery and development of IP3 receptor modulators are also described.Expert opinion Despite significant progress in recent years, the pharmacology of IP3R still has major drawbacks, especially concerning the availability of specific antag onists. Moreover, drugs specifically targeting the three different subtypes of IP3R are especially needed.Background To investigate how EHD2 influences the development of colon cancer.Methods Immunohistochemistry of 90 colon cancer tissue specimens were determined the expression of EHD2. The lentivirus-EHD2-transfected colon cancer cells were conducted to evaluate the biological behaviors.Results EHD2 was closely associated with clinic pathological parameters (p  less then  0.001). EHD2 upregulation was relative with a longer overall survival. The results of the univariate and multivariate analyses indicated that EHD2 could be an independent prognosis marker. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest.Conclusions EHD2 might represent a therapeutic target of colon cancer.IMPACT STATEMENTWhat is already known on this subject? Membrane trafficking is crucial for cell proliferation, differentiation and apoptosis, especially tumorigenesis and development. anti-HER2 antibody inhibitor EHD2 proteins play an important role in the regulation of membrane trafficking in endocytosis. EHD2 has been suggested to participate in the occurrence of some malignancies.What are the new findings? EHD2 could be an independent prognosis marker in colon cancer. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest in vitro. EHD2 overexpression markedly increased the expression of EMT marker E-cadherin in colon cancer.How might it impact on clinical practice in the foreseeable future? EHD2 overexpression may inhibit tumorigenesis in colon cancer through the modulation of E-cadherin, the critical marker of EMT which is closely related to invasion and distant metastasis of tumor cells. To evaluate conservative treatment of giant lumbar disc herniation in patients with extreme pain and to assess temporal changes in pain levels and radiological findings with short-term follow-up. A total of 15 patients with severe pain (as measured by visual analog scale [VAS]) due to giant lumbar disc herniation and without neurological deficits were included. All patients received conservative treatment and were followed weekly for pain and medication assessment. MRI was performed at baseline, second month and fourth month to calculate disc herniation volume. The changes in disc herniation and pain were evaluated. There was no relationship between pain and the regression of disc herniation in these five females and ten males with a mean age of 41.4years. MRI results showed an average of 20.3% and 20.4% regression of disc herniation from baseline to second month, and second month to fourth month, respectively. Whereas, pain levels had reduced from an average of 90.8-13.53 by the second month, and to 3.