Artificial intelligence-based drug development: current progress and future challenges / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Application of a novel modified Blumgart anastomosis in laparoscopic pancreaticoduodenectomy / 中国医师进修杂志

Objective:To investigate the efficacy and safety of a novel modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD).Methods:Between May 2021 and January 2022, 13 successive cases from Lihuili Hospital Affiliated to Ningbo University who underwent LPD were enrolled in this retrospective study. The study retrospectively analyzed the demographic characteristics, perioperative outcomes, and pathological results of these cases.Results:Twenty patients underwent LPD success-fully and one required conversion to open surgery. The operative time was (308.6 ± 61.7) min. The duration for PJ was (26.7 ± 4.3) min. The estimated blood loss was (188.1 ± 94.2) ml. The postoperative hospital stay was (14.2 ± 3.5) d. There was one case of biochemical leakage and no case of grade B or grade C pancreatic fistula.Conclusions:The new method is safe, simple and feasible. The novel method could reduce the incidence of pancreatic fistula and other complications after LPD.

Full Endoscopic Lumbar Discectomy Versus Laminectomy for Cauda Equina Syndrome.

BACKGROUND: Typically, open surgery is advocated for cauda equina patients. The goal of this study was to compare the clinical efficacy of full endoscopic lumbar discectomy and laminectomy in the treatment of cauda equina syndrome (CES) caused by lumbar disc herniation. METHODS: Forty-three patients with CES either underwent endoscopic or laminectomy surgery from May 2015 to April 2016, and data were collected and retrospectively analyzed. The patients were divided into 2 groups according to the surgical methods: the endoscopy group (with 21 patients, 14 males and 7 females, and an average age of 42.67 with a standard deviation of 9.70 years) and the laminectomy group (with 22 patients, 16 males and 6 females, and an average age of 44.55 with a standard deviation of 9.36 years). The modified Japanese Orthopaedic Association (JOA) "leg-trunk-bladder" score was used to assess the efficacy of the respective surgical methods. RESULTS: Analysis showed longer surgery time, more bleeding, and longer hospital stay in the laminectomy group than in the endoscopy group with statistical significance. The postoperative JOA scores improved in both groups when compared with those before the operation, and the differences were statistically significant. There were no significant differences in JOA scores between the 2 groups at preoperation and 6-month and 1-year follow-ups. There was 1 patient in each group whose CES symptoms worsened after endoscopy. However, immediate reoperation resulted in satisfactory outcomes. CONCLUSIONS: CES clinical symptom resolution was equal with endoscopy and laminectomy both in short-term and midterm follow-up. However, endoscopic treatment was advantageous by reducing the amount of bleeding, duration of surgery, and hospitalization days when compared to laminectomy. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: Feasibility study Endoscopic Decompression for Cauda Equina.

Seawater Immersion Aggravates Early Mitochondrial Dysfunction and Increases Neuronal Apoptosis After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability in naval warfare. Due to the unique physiochemical properties of seawater, immersion in it exacerbates TBI and induces severe neural damage and complications. However, the characteristics and underlying mechanisms of seawater-immersed TBI remain unclear. Mitochondrial dysfunction is a major cause of TBI-associated brain damage because it leads to oxidative stress, decrease in energy production, and apoptosis. Thus, the present study aimed to further elucidate the current understanding of the pathology of seawater-immersed TBI, particularly the role of mitochondrial dysfunction, using a well-defined rat model of fluid percussion injury and a stretch injury model comprising cultured neurons. The biochemical and pathological markers of brain-related and neuronal injuries were evaluated. Histological analysis suggested that seawater immersion enhanced brain tissue injury and induced a significant increase in apoptosis in rats with TBI. Additionally, lactate dehydrogenase release occurred earlier and at higher levels in stretched neurons at 24 h after seawater immersion, which was consistent with more severe morphological changes and enhanced apoptosis. Furthermore, seawater immersion induced more rapid decreases in mitochondrial membrane potential, adenosine triphosphate (ATP) content, and H+-ATPase activity in the cortices of TBI rats. In addition, the immunochemical results revealed that seawater immersion further attenuated mitochondrial function in neurons exposed to stretch injury. The increases in neuronal damage and apoptosis triggered by seawater immersion were positively correlated with mitochondrial dysfunction in both in vivo and in vitro models. Thus, the present findings strengthen the current understanding of seawater-immersed TBI. Moreover, because seawater immersion aggravates mitochondrial dysfunction and contributes to post-traumatic neuronal cell death, it is important to consider mitochondria as a therapeutic target for seawater-immersed TBI.

Effect of GEPT extracts on spatial learning ability of APPV717I transgenic mice at early stage of dementia and its possible mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of GEPT extracts on spatial learning ability of the APPV717I transgenic mice at the early stage of dementia and its possible mechanism.</p><p><b>METHOD</b>Thirty APPV717I transgenic mice were randomly divided into three GEPT groups by intragastric administration at doses of 0.075, 0.15, 0.3 g x kg(-1) x d(-1), and a donepezil group by intragastric administration of 0.92 mg x kg(-1) x d(-1), a APPV717I transgenic model group and a normal group by intragastric administration of distilled water. A four-month treatment regimen with GEPT extracts was administered to APPV717I transgenic mice. Results showed that Spatial memory ability was measured in Morris water maze. The total area covered by shank1 and integral optical density in CA1 subfield within the hippocampus were determined using immunohistochemical stains and Image-Pro plus analysis. The ultrastructure of synapses in the hippocampal CA1 region was observed by electronic microscope.</p><p><b>RESULT</b>After a four-month of GEPT treatment regimen, the mean escape latency period were significantly shortened (P < 0.05), and the target quadrant search time were significantly increased (P < 0.05) compared to the APPV717I transgenic model mice. There was a significant higher level in the expression of shank1 detected in the hippocampal CA1 area of APPV717I transgenic mice associated with an increase in the number of synapses treated with GEPT than the levels in the APPV717I transgenic model mice alone. The total area of positive cells covered by shank1 and their integral optical density in the hippocampal CA1 area of the APPV717I transgenic mice treated with GEPT were significantly increased more than those of the APPV717I transgenic model mice.</p><p><b>CONCLUSION</b>GEPT extracts can obviously improve the spatial memory ability of APPV717I transgenic mice at the early stage of dementia through enhancing the number of synapses and the expression of shank1, and this might lead to development of novel treatment therapies for the memory loss associated with AD.</p>