Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective:To compare the perioperative conditions of open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD) and LPD conversion OPD, and analyze the short-term prognosis and risk factors for LPD conversion OPD.Methods:The clinical data of 167 patients undergoing pancreaticoduodenectomy (PD) in the Beijing Friendship Hospital, Capital Medical University from February 2020 to March 2023 were retrospectively analyzed. Of 167 patients, 63 patients underwent OPD surgery (OPD group), 91 patients underwent LPD surgery (LPD group), and 13 patients were converted to OPD during LPD surgery (LPD conversion OPD group). The measurement data with non-normal distribution were expressed as median (interquartile range) [ M( Q1, Q3)], and comparison between groups was analyzed using the Kruskal-Wallis H test. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for ordered categorical variable, Kruskal-Wallis H test was used for un-ordered categorical variable. The risk factors of LPD conversion OPD were analyzed by multivariate Logistic regression. Results:The intraoperative blood loss [600(350, 1 000) mL], bilio-intestinal drainage stay time [10(8, 15) d] and bilio-intestinal drainage volume [995(505, 1 502) mL] in the LPD conversion OPD group were significantly higher than those in the LPD group [200(100, 300) mL, 7(6, 6) 10) d, 450(175, 874) mL], the differences were statistically significant ( P<0.05). The operation time of the LPD conversion OPD group [335(293, 385) d] was significantly longer than that of the OPD group [230 (195, 290)d], and the difference was statistically significant ( P<0.05). Multivariate Logistic regression analysis revealed that preoperative complications of chronic pancreatitis ( OR=19.714) and maximum diameter of the lesion ( OR=5.583) has a significant impact on the LPD conversion OPD ( P<0.05). Conclusions:Patients who plan to undergo PD should prefer LPD if the technology and physical condition permit. Preoperative complication of chronic pancreatitis, maximum diameter of lesion > 3.5 cm are the risk factors for LPD conversion OPD, which may significantly increase intraoperative blood loss, prolong the indwelling time of biliary drainage tube, and increase the drainage volume of biliary drainage tube. Therefore, the surgical method should be carefully selected.

The spirit of Norman Bethune was formed during the period of the Comprehensive Anti-Japanese War, and played an important role in shaping thought and promoting foreign exchanges in the subsequent inheritance and development process. Promoting the spirit of Norman Bethune in the context of sudden public health crisis, relying on its spiritual strength and extensive influence, and in line with China’s anti-epidemic experience, explaining its principles, methods, organizations, driving forces, and exemplary experiences, so that the Norman Bethune spirit can be promoted and developed in the context of sudden public health crisis, giving its a strong contemporary appeal.

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.
Acid Sensing Ion Channels/physiology* ; Animals ; HEK293 Cells ; Humans ; Pressoreceptors/physiology* ; Rats ; TRPV Cation Channels/physiology*

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch–aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch–aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

Objective To explore the effects of ingestion training based on food form modification on improving swallowing function among swallowing disorder patients after stroke. Methods From January 2018 and June 2019,this study selected 80 swallowing disorder patients after stroke of Department of Rehabilitation at Xuanwu Hospital Capital Medical University as subjects by convenience sampling.All of patients were divided into control group and observation group with the random number table,40 cases in each group.Control group carried out routine ingestion training. On the basis of that,observation group implemented ingestion training based on food form modification. The swallowing function was evaluated with the Modified Mann Assessment of Swallowing Ability(MMASA)before and after treatment. At the same,the rates of complication incidences and nutritional status were observed between two groups. Results After intervention,the score of MMASA of observation group were(144.10±16.56)higher than that(136.48±13.56)of control group with a statistical difference(P<0.05);the incidences of aspiration and pulmonary infection of observation group were lower and serum albumin was higher than those of control group with statistical differences(P<0.05). However,there was no statistical difference in the body mass index(BMI)between two groups(P>0.05). Conclusions Ingestion training based on food form modification and swallowing training can promote the recovery of swallowing function among swallowing disorder patients after stroke and reduce the incidences of complication which has a positive role in the prognosis of patients.

Objective To study the MSCT findings of pulmonary lymphoma,and improve its imaging diagnostic accuracy.Methods The MSCT findings of 14 patients with pathologically proven pulmonary lymphoma were reviewed retrospectively.Evaluated imaging findings included distribution position,number,shape,density and accompanying signs of the lesion.Results In 14 cases of pulmonary lymphoma,except for miliary shadow,there were 108 lesions,including small nodules,nodules,masses,consolidation,ground-glass density and meshlike shadow.Solitary lesions were founded in 2 and multiple lesions were founded in 12 of 14 cases,which the multiple lesions found in single lung in 3 cases,and multiple lesions found in both lungs in 9 cases.There were 24 lesions in 7 cases of pulmonary consolidation, including air bronchogram in 6 cases and bronchiectasis in 3 cases.There were 7 cases with masses,5 cases with nodules,5 cases with small nodules,2 cases with ground-glass density,2 cases with pulmonary interstitial changes,2 cases with CT angiogram sign,4 cases with pleural effusion and 3 cases with mediastinal or pulmonary hilar lymphadenopathy.Conclusion The mainly MSCT findings of pulmonary lymphoma was pulmonary consolidation with air bronchogram,or masses,or nodules,or multiple signs exist at the same time.The diagnosis is mainly based on histopathology.

Objective To investigate the effect of different time intervention of Zhu Lian acupuncture exciting method on nerve cell apoptosis and tissue expressions of PI3K (phosphatidylinositol 3-kinase), AKt (serine/threonine kinase) and Caspase-3 (cysteinyl aspartate specific proteinase-3) proteins in young rats with hypoxic-ischemic brain damage.Methods Fifty 7-day-old rats were randomized into groups A (acupuncture exciting methodⅠ), B (acupuncture exciting methodⅡ), C (model), D (sham operation) and E (normal control), 10 rats each. Groups A and E began to receive acupuncture in 24 hours after model making and group B, at 8 days after model making. Groups C and D were not given acupuncture. Every group of animals was sacrificed at 21 days after model making. Nerve cell apoptosis was examined using In situ end labeling (TUNEL) technique. Cerebral expressions of PI3K, AKt and Caspase-3 proteins were determined by immunohistochemical method.Results The number of apoptotic cells was significantly smaller in groups A and B than in group C (P<0.01,P<0.05) and decreased significantly in group A compared with group B (P<0.05). The expressions of PI3K and AKt proteins increased significantly and the expression of Caspase-3 protein decreased significantly in groups A and B compared with group C; there were statistically significant differences (P<0.01,P<0.05). PI3K expression increased significantly and Caspase-3 protein expression decreased significantly in group A compared with group B (P<0.05); there were statistically significant differences (P<0.05).Conclusions Zhu Lian acupuncture exciting method can inhibit nerve cell apoptosis, stimulate the expression of PI3K/AKt signaling pathway, increase PI3K and AKt activities and reduce the expression of Caspase-3 protein in young rats with hypoxic-ischemic brain damage. Early intervention of Zhu Lian acupuncture exciting method is of important significance in producing a protective effect on brain nerves in young rats with hypoxic-ischemic brain damage.

Objective To study the effects ofShenqi YizhiGranules (SQYZ) on learning and memory and content of Aβ1-42 of cerebral tissue in 5XFAD mice with Alzheimer’s disease; To discuss its mechanism on improving learning and memory ability of 5XFAD mice.Methods Four-month-old C57BL?6 wild type mice were randomly divided into NS control group and SQYZ control group, and the 5XFAD mice were randomly divided into model group, SQYZ group and huperzine-A (HupA) group, 15 mice in each group. Each group were given same volume for gavage for 60 d. After treatment, the learning and memory ability were evaluated by nesting test, passive avoidance and Morris water maze test. The senile plaques and content of Aβ1-42, ionized calcium binding adapter molecule 1 and glial fibrillary acidic protein in cerebral cortex and hippocampus were detected by immunohistochemical staining and immunofluorescence, respectively.Results Compared with NS control group, the score of nesting test in model group significantly decreased; the step-through latency in passive avoidance was shortened and the escape latentcy in Morris water maze test was prolonged; the quantity of senile plaques and content of Aβ1-42 increased in cerebral cortex and hippocampus; the activation of glial cells significantly increased. In the SQYZ group, the above-mentioned indexes reached or approached the level of wild type control mice. The difference between SQYZ group and model group was statistically significant (P<0.05,P<0.01).Conclusion SQYZ improved learning and memory ability in 5XFAD mice, which may be related to reduction of senile plaques, inhibition of over activation in glial cells and reduction of content of Aβ1-42 in cerebral cortex and hippocampus.