Analysis of Patents Issued in China for Antihyperglycemic Therapies for Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is prevalent, with a dramatic increase in recent years. Moreover, its microvascular and macrovascular complications cause significant societal issues. The demand for new and effective antidiabetic therapies grows with each passing day and motivates organizations and individuals to pay more attention to such products. In this article, we focused on oral antihyperglycemic drugs patented in China and introduced them according to their antihyperglycemic mechanisms. By searching the website of State Intellectual Property Office of the People’s Republic of China (http://www.sipo.gov.cn), 2,500 antihyperglycemic patents for T2DM were identified and analyzed. These consisted of 4 patents for derivatives of herbal extracts (0.2%), 162 patents for herbal extracts (6.5%), 61 compositions for traditional Chinese medicine (TCM) (2.4%), 2,263 patents for synthetic compounds (90.5%), and 10 (0.4%) patents of the combination of synthetic compounds and TCM. As the most common drugs for diabetes mellitus, synthetic compounds can also be classified into several categories according to their working mechanisms, such as insulin secretion promotor agents, insulin sensitizer agents, α-glucosidase inhibitors, and so forth. This article discussed the chemical structure, potential antihyperglycemic mechanism of these antihyperglycemic drugs in patents in China.Expert opinion: Insulin sensitivity and β-cell function could be improved by weight loss to prevent prediabetes into T2DM. However, 40–50% patients with impaired glucose tolerance (IGT) still progress to T2DM, even after successful long-term weight loss.Antihyperglycemic remedies provide a treatment option to improve insulin sensitivity and maintain β-cell function. Combination therapy is the best treatment for diabetes. Combination therapy can reduce the dosage of each single drug option, and avoid the side effects. Drugs with different mechanisms are complementary, and are better adapted to patients with changing conditions. Classical combination therapies include combinations such as sulfonylureas plus biguanides or glucosidase inhibitors, biguanide plus glucosidase inhibitors or insulin sensitizers, insulin treatment plus biguanides or glucosidase inhibitors. The general principle of combination therapy is that two drugs with different mechanisms are selected jointly, and the combination of three types of hypoglycemic drugs is not recommended. After reading a large amount of literature, we have rarely found a case of three oral hypoglycemic agents, which may mean that the combination of three oral hypoglycemic agents is unnecessary and has unpredictable risks. There is no objection to the idea of multi-drug therapy. But multiple drugs can only be used when it shows a significant benefit to the patients. Combined use of multiple antidiabetic drugs poses a risk to patients due to drug interactions and overtreatment

Effects of acupuncture or similar needling therapy on pain, proprioception, balance, and self-reported function in individuals with chronic ankle instability: A systematic review and meta-analysis

Objective: Acupuncture or similar needling therapy has long been used to improve well-being, but its effectiveness in management of chronic ankle instability (CAI) is unclear. To investigate the efficacy of acupuncture or similar needling therapy on pain, proprioception, balance, and self-reported function in individuals with CAI. Methods: Nine databases (PubMed, Embase, Cochrane Library, Web of Science, EBSCO, PEDro, CNKI, WanFang, and CQVIP) were systematically searched from inception to April 2023. This study included randomized controlled trials involving acupuncture or similar needling therapy as an intervention for individuals with CAI. Data were extracted independently by two assessors using a standardized form. Literature quality and risk bias were assessed by using the PEDro scale. Results: Twelve trials (n = 571) were found, of which the final meta-analysis was conducted with eight. Different studies employ varying treatments, including specific needle types, techniques, and therapeutic frameworks. Compared to control without acupuncture or similar needling therapy, acupuncture or similar needling intervention resulted in improved pain (WMD 1.33, 95 % CI 0.14–2.52, I²=90 %, p = 0.03), proprioception (active joint position sense, WMD 1.71, 95 % CI 0.95–2.48, I²=0 %, p < 0.0001), balance (SMD 0.54, 95 % CI 0.03–1.04, I²=46 %, p = 0.04), and self-reported function (Cumberland Ankle Instability Tool (WMD 2.92, 95 % CI 0.94–4.90, I²=78 %, p = 0.004); American Orthopedic Foot and Ankle Society (WMD 9.36, 95 % CI 6.57–12.15, I²=0 %, p < 0.001); Foot and Ankle Ability Measure: activities of daily living (WMD 5.09, 95 % CI 1.74–8.44, I²=0 %, p = 0.003)) for individuals with CAI. Conclusions: The available evidence suggests that acupuncture or similar needling therapy may improve pain, proprioception, balance, and self-reported function in individuals with CAI, but more trials are needed to verify these findings. Furthermore, various needles and techniques using in different studies have resulted in methodologic limitations that should be addressed in the future

Synthesis and Comparative Biological Properties of Ag-PEG Nanoparticles with Tunable Morphologies from Janus to Multi-Core Shell Structure

Silver nanoparticles synthesized with polymers as coating agents is an effective method to overcome their poor stability and aggregation in solution. Silver-polyethylene glycol (Ag-PEG) nanoparticles were synthesized with the thiol-functionalized polyethylene glycol (SH-PEA) as the coating, reducing and stabilizing agent. The UV irradiation time, polymer and silver nitrate concentration for the synthesis were investigated. The concentration of silver nitrate had significant effect on the morphology of Ag-PEG nanoparticles. When increasing the concentration of silver nitrate, SEM and TEM images showed that Ag-PEG nanoparticles changed from Janus to multi-core shell structure. Meanwhile, pure silver particles in the two hybrid nanoparticles presented spherical shape and had the similar size of 15 nm. The antibacterial activities and cytotoxicity of the two structural Ag-PEG nanoparticles were investigated to understand colloid morphology effect on the properties of AgNPs. The results of antibacterial activities showed that the two structural Ag-PEG nanoparticles exhibited strong antibacterial activities against Staphylococcus aureus, Escherichia coli and Bacillus subtilis. The Janus nanoparticles had larger minimal inhibitory concentration (MIC) and minimum bacterial concentration (MBC) values than the multi-core shell counterparts. The results of cytotoxicity showed the Janus Ag-PEG nanoparticles had lower toxicity than the multi-core shell nanoparticles

Impact of inner ear malformation and cochlear nerve deficiency on the development of auditory-language network in children with profound sensorineural hearing loss

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide partial hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to patients with profound hearing loss as no auditory brainstem responses can be detected in these individuals, making it impossible to capture corresponding blood oxygen signals in fMRI. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under 6 years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, showing significant correlations between age, gender, Cn.VIII median contrast value, and the language network with post-implant qualitative outcomes