Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

BACKGROUND:Hippocampal injury caused by aortic coarctation has been poorly studied,and combined detection of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 expression in aortic dissection has not been reported.OBJECTIVE:To observe histomorphologic changes in the hippocampus of a mouse model of aortic dissection and investigate the expression and significance of tumor necrosis factor alpha,nuclear factor kappaB and ionized calcium binding adaptor molecule-1 in the hippocampus of aortic dissection mice.METHODS:Sixteen healthy 3-week-old male C57BL/6 mice were randomly divided into two groups:control group and aortic dissection group,with eight mice in each group.In the aortic dissection group,mice were given β-aminopropionitrile monofumarate as drinking water for 4 weeks,and the angiotensin Ⅱ microinfiltration pump was then implanted to establish an animal model of aortic dissection.Mice in the control group were given normal diet and water.After the model was established,the maximum diameter of the ascending aorta was measured,hematoxylin-eosin staining and EVG staining were performed to evaluate the model formation rate,and the levels of inflammatory factors tumor necrosis factor α and interleukin 6 in serum were detected by enzyme-linked immunosorbent assay.The hippocampus was dissected and stained with hematoxylin-eosin to observe the pathological changes of the hippocampus in brain sections.The protein expression of tumor necrosis factor α,nuclear factor κB and ionized calcium binding adaptor molecule-1 was detected by western blot analysis.RESULTS AND CONCLUSION:(1)Compared with the control group,the maximum diameter of the ascending aorta in the aortic dissection group was significantly enlarged.(2)Hematoxylin-eosin staining of the aorta showed obvious thickening of the middle aorta and destruction and disorder of the aortic wall structure in mice.Neurons in the CA1 and CA3 regions of mice were sparsely arranged,reduced in size,and showed pyknosis with deeply stained nuclei.(3)Serum levels of inflammatory factors tumor necrosis factor α and interleukin 6 were increased in the aortic dissection group compared with the control group(P＜0.01).(4)The expression levels of tumor necrosis factor α,nuclear factor κB,phosphorylated nuclear factor κB,and ionized calcium binding adaptor molecule-1 in the hippocampus were increased in the aortic dissection group compared with the control group(P＜0.05).To conclude,microglial activation and increased expression of tumor necrosis factor α and nuclear factor κB may be involved in hippocampal neuron injury in aortic dissection mice.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism* ; Fermentation ; Glycine max/metabolism* ; Soybean Proteins/metabolism* ; Peptide Hydrolases/metabolism* ; Ribosomes/metabolism* ; Globulins ; Antigens, Plant ; Seed Storage Proteins

Objective:To compare the preoperative presentation, intraoperative findings, and postoperative outcomes between middle ear cholesteatoma with tympanosclerosis （MECwTS） and middle ear cholesteatoma without tympanosclerosis （MECw/oTS）, thereby investigating the clinical characteristics of MECwTS. Methods:A retrospective analysis was conducted on the clinical data of 120 patients with middle ear cholesteatoma. Patients were divided into two groups based on the presence or absence of concomitant tympanosclerosis: the MECwTS group （n=49） and the MECw/oTS group （n=71）. All patients underwent preoperative evaluations including temporal bone CT, otoscopic examination, pure-tone audiometry, tympanometry, and assessment using the Zurich Chronic Middle Ear Inventory （ZCMEI-21） quality of life scale. All patients underwent canal wall down mastoidectomy with tympanoplasty. Concurrent ossicular chain reconstruction was performed: partial ossicular replacement prosthesis （PORP） in 83 cases and total ossicular replacement prosthesis （TORP） in 37 cases. Intraoperative disease severity was assessed using the Cholesteatoma Comprehensive Score Scale （CCSS）. Postoperative follow-up lasted at least one year and included pure-tone audiometry, otoscopic examination, and the ZCMEI-21 scale administered at ≥1 year post-surgery. Preoperative and postoperative air-bone gap （ABG） and ZCMEI-21 scores were compared between the MECwTS and MECw/oTS groups. Additionally, surgical efficacy was defined as a postoperative ABG ≤20 dB; the hearing improvement efficacy of PORP versus TORP was compared based on this criterion. Results: ①Preoperative ABG showed no significant difference between the MECw/oTS and MECwTS groups（P>0.05）. Postoperative ABG was （18.65±10.21） dB in the MECw/oTS group versus （22.55±9.53） dB in the MECwTS group, demonstrating a statistically significant intergroup difference （P<0.05）. ②Intraoperative CCSS scores were significantly higher in the MECwTS group （8.04±2.18） compared to the MECw/oTS group （5.93±1.44） （P<0.05）. ③Preoperative ZCMEI-21 scores showed no significant difference between groups （P>0.05）. Postoperative ZCMEI-21 scores were （22.24±8.11） in the MECw/oTS group versus （27.02±7.21） in the MECwTS group, indicating a statistically significant difference （P<0.05）. ④Postoperative ABG ≤20 dB was achieved in 54 patients （65.06%, 54/83） in the PORP group and 16 patients （43.24%, 16/37） in the TORP group. This difference in efficacy rates was statistically significant （P<0.05）. The overall efficacy rate for ossiculoplasty was 58.33% （70/120）. Conclusion: Patients with MECwTS exhibit more severe middle ear and mastoid pathology compared to those with MECw/oTS, resulting in poorer postoperative hearing levels and quality of life outcomes. Both PORP and TORP implantation can improve postoperative hearing to some extent; however, PORP appears to offer superior hearing improvement efficacy compared to TORP.
Humans ; Cholesteatoma, Middle Ear/complications* ; Retrospective Studies ; Tympanoplasty ; Myringosclerosis/surgery* ; Female ; Male ; Adult ; Middle Aged ; Ossicular Replacement ; Ossicular Prosthesis ; Young Adult ; Ear, Middle ; Treatment Outcome ; Mastoidectomy ; Audiometry, Pure-Tone ; Adolescent ; Quality of Life

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.