OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.

OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.

ObjectiveTo observe the clinical effect of Danshenyin on chronic atrophic gastritis and explore the mechanism. MethodA total of 152 patients with chronic atrophic gastritis who were treated in Xining No. 1 People's Hospital were selected and randomized into control group （76 cases） and observation group （76 cases）. The control group was given conventional western medicine treatment， and the observation group was given Danshenyin （oral）. The treatment lasted 8 weeks for both groups. The clinical effect， traditional Chinese medicine （TCM） syndrome score， and pathological score of gastric mucosa were compared between two groups. The content of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， proinflammatory cytokines ［soluble interleukin-2 receptor （sIL-2R）， tumor necrosis factor-α （TNF-α）］， and gastric mucosa-proteting factors ［prostaglandin E₂ （PGE₂）， calcitonin gene-related peptide （CGRP）］ was determined， and the adverse reactions and recurrence rates were recorded. ResultThe effective rate （91.18%， 62/68） in the observation group was higher than that （7.61%， 52/67） in the control group （χ²=4.727， P<0.05）. The TCM syndrome score in the observation group was lower than that in the control group （P<0.05）. Compared with the control group， the observation group showed low pathological scores of glandular atrophy and intestinal metaplasia and dysplasia （P<0.05）. The observation group had higher serum PGⅠ content and PGⅠ/PGⅡ value and lower PGⅡ content than the control group （P<0.05）. The content of sIL-2R and TNF-α decreased （P<0.05） and that of PGE₂ and CGRP increased （P<0.05） in the observation group as compared with those in the control group. The incidence of adverse reactions in the observation group was 7.35% （5/68）， as compared with the 14.93% （10/67） in the control group. The recurrence rates in the 6-month and 12-month follow-up in the observation group were lower than those in the control group， but the difference was not statistically significant （Fisher's exact test）. ConclusionDanshenyin shows satisfactory effect in relieving TCM syndrome， regulating PG secretion， and improving gastric mucosal lesions in the treatment of chronic atrophic gastritis. The mechanism is the likelihood that it modulates sIL-2R， TNF-α， PGE₂， and CGRP to alleviate inflammatory damage of gastric mucosa and protect gastric mucosa. The medicine is safe and reduces the recurrence of chronic atrophic gastritis.

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.

Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error methods of pharmaceutical scientists. This approach is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. The aim of the present research is to apply deep learning methods to predict pharmaceutical formulations. In this paper, two types of dosage forms were chosen as model systems. Evaluation criteria suitable for pharmaceutics were applied to assess the performance of the models. Moreover, an automatic dataset selection algorithm was developed for selecting the representative data as validation and test datasets. Six machine learning methods were compared with deep learning. Results showed that the accuracies of both two deep neural networks were above 80% and higher than other machine learning models; the latter showed good prediction of pharmaceutical formulations. In summary, deep learning employing an automatic data splitting algorithm and the evaluation criteria suitable for pharmaceutical formulation data was developed for the prediction of pharmaceutical formulations for the first time. The cross-disciplinary integration of pharmaceutics and artificial intelligence may shift the paradigm of pharmaceutical research from experience-dependent studies to data-driven methodologies.

Most pharmaceutical formulation developments are complex and ideal formulations are generally obtained after extensive experimentation. Machine learning is increasingly advancing many aspects in modern society and has achieved significant success in multiple subjects. Current research demonstrated that machine learning can be adopted to build up high-accurate predictive models in drugs/cyclodextrins (CDs) systems. Molecular descriptors of compounds and experimental conditions were employed as inputs, while complexation free energy as outputs. Results showed that the light gradient boosting machine provided significantly improved predictive performance over random forest and deep learning. The mean absolute error was 1.38 kJ/mol and squared correlation coefficient was 0.86. The evaluation of relative importance of molecular descriptors further demonstrated the key factors affecting molecular interactions in drugs/CD systems. In the specific ketoprofen-CD systems, machine learning model showed better predictive performance than molecular modeling calculation, while molecular simulation could provide structural, dynamic and energetic information. The integration of machine learning and molecular simulation could produce synergistic effect for interpreting and predicting pharmaceutical formulations. In conclusion, the developed predictive models were able to quickly and accurately predict the solubilizing capacity of CD systems. Current research has taken an important step toward the application of machine learning in pharmaceutical formulation design.

Objective To investigate the application of middle segment pancreatectomy (MSP) in treating benign pancreatic tumors and the effect on exocrine function.Methods From Jan.2010 to Feb.2013,19 cases with benign pancreatic tumor undergoing MSP were enrolled in our study.Pre-and postoperative pancreatic exocrine function were studied.Results No perioperative death happened.The tumor diameter was 4.2 to 7.0cm,operative time was 80 to 320 mins,and intraoperative blood loss was 200 to 1000 ml.The retained pancreas was＞l.5 cm at pancreatic head side,and＞5 cm at pancreatic caudal side.Three days after surgery,the peritoneal drainage and amylase was 2.5-12.5 ml and 568.4-1013 IU/L,respectively.Seven days after surgery,the peritoneal drainage and amylase was 1.0-19.8 ml and 45.4-76.3 IU/L,respectively.The postoperative hospitalization stay were 10 to 25 days.Three cases (all single anastomosis) had pancreatic fistula after surgery and healed after 3 months without undergoing surgery again.Patients were followed up for 2 months to 3 years.All patients have a good life quality,without new-onset diabetes and cancer recurrence.MSP had no side effects on pancreatic exocrine function.Conclusion MSP is safe and feasible in treatment of benign pancreatic tumors.

Objective:To explore the role and mechanisms ofω-3 polyunsaturated fatty acids (ω-3PUFAs) alone or in combination with dexamethasone (DEX) in inducing cell apoptosis and reversing drug resistance in multiple myeloma (MM). Methods:DEX-resistant MM cell line MM1R was treated with different concentrations of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) alone or in combination with DEX for 24 or 48 h. Cel proliferation was detected by MTT assay. Cel cycle and apoptosis were measured by flow cytometry. Expression levels of apoptosis-related proteins were analyzed by Western blot. Two-tailed, unpaired Student's t-test was used to compare the two treatment groups. A value of P<0.05 was considered statistically significant. Results:MM1R proliferation was inhibited by different concentrations (10, 20, 50, and 100μM) of EPA or DHA alone or in combination with 10μM DEX in a dose-and time-dependent manner. The inhibition effect was significantly higher in combinative groups than in single EPA or DHA treatment group (P=0.014, P=0.032). The percentage of G0/G1 phase and cell apoptosis rate in MM1R treated with different concentrations of EPA or DHA alone increased in a dose-dependent manner. This percentage was also significantly higher in the combinative groups than in the single EPA or DHA treatment group (P=0.015, P=0.004). The expression levels of cleaved caspase-3 and Bax were upregulated, whereas those of pro-caspase-3 and BCL-2 were downregulated in a dose-dependent manner. Drug resistance gradually decreased in MM1R cells at different concentrations of EPA or DHA with the increase of drug concentration. The reversal fold also increased gradual y, whereas the cel s decreased in the two drug-combination groups compared with the single-drug group. Moreover, the drug-resistance reversal index increased significantly. Conclusion:ω-3PUFAs can inhibit DEX-resistant MM cell proliferation, arrest cell cycle, and induce cell apoptosis.ω-3PUFAs also exhibit a synergistic anti-resistanteffect in combination with DEX. Furthermore,ω-3PUFAs can serve as novel effective drugs for MM treatment.

BACKGROUND:Static cold storage is the main storage method of liver transplantation in the past 40 years. There are success cases in foreign countries about the use of mechanical reperfusion in liver transplantation, but there is no large-scale development in China. OBJECTIVE:To investigate and compare the inflammatory cytokines and apoptotic factors in isolated liver between static cold storage and hypothermic machine perfusion before and after liver transplantation. METHODS:There were donor group, static cold storage group and hypothermic machine perfusion group in the study, and 30 dogs were in each group. Liver specimens from donor dogs were subjected to static cold storage and then transplanted into dogs in the static cold storage group. Liver specimens from dogs in the static cold storage group were subjected to hypothermic machine perfusion and then transplanted into dogs in the hypothermic machine perfusion group. Liver specimens from dogs in the hypothermic machine perfusion were used in other experiments. Dogs in the donor group were euthanatized. After liver transplantation, 20 dogs from static cold storage group and hypothermic machine perfusion group were selected respectively for further study. RESULTS AND CONCLUSION: When the liver was separated from the dogs, inflammatory cytokines and apoptosis factors had no significant difference in the static cold storage group and hypothermic machine perfusion group (P > 0.05). P53 expression in these two groups had no significant difference before and after transplantation (P > 0.05). Interleukin-1βand interleukin-8 in these two groups had no significant difference before transplantation (P > 0.05). Compared with the static cold storage group, expressions of tumor necrosis factor-α, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, CC chemokine ligand 20 and FASR were significantly lower in the hypothermic machine perfusion group before transplantation (P< 0.01). Compared with the static cold storage, interleukin-1β, tumor necrosis factor-α, interleukin-8, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, CC chemokine ligand 20, FASR and nuclear factor-κB were reduced significantly in the hypothermic machine perfusion group at 60 minutes after transplantation (P < 0.01). Taken together, hypothermic machine perfusion can significantly reduce inflammatory cytokines and apoptosis factor, which is conducive for liver transplantation.

Cystic echinococcosis is one of the most widespread and severe zoonotic helminthic diseases .To understand the phylogeny and genetic polymorphism Echinococcus granulosus (E .granulosus) prevailed in south region of Qinghai Prov-ince ,partial fragment of cytochrome oxidase Ⅰ (COX Ⅰ ) gene sequences were used to infer the phylogenetic relationship of 59 collected samples of E .granulosus in Qinghai Province .Total 72 sequences (13 sequences from GenBank) were aligned using CLUSTAL X ,and then ,Bayesian analyses were performed in Mrbayes-3 .1 .2 .The results revealed that Echinococcus spp .isolates did not form a monophyletic group .The most samples clustered with E . granulosus strain (G1) (AB297617) , but showed high genetic polymorphism .Another three samples clustered with E .multilocularis (AB018440) ,while they showed complex phylogenetic relationships among them ,further indicating that Echinococcus spp .isolates from Qinghai Prov-ince may has a more complex evolutionary history than expected .