Purpose: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. Materials and Methods: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). Results: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). Conclusion Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Insomnia is an important problem facing the global public health field,presenting high morbidity and low treatment efficiency,while Tibetan medicine has rich clinical experience in treating insomnia,showing certain regional characteristics.The article adopts the method of documentary evidence to trace and analyse the diagnosis and treatment theories of Tibetan doctors on insomnia through the ages,It was found that due to three functional disorders,Bacon's inability to concentrate on the heart was the main pathogenesis of the disease,and divides into Tsh yer,Grng yer,and Gdon yer,three mainstream types of evidence.The treatment method adopted the traditional"quadruple"therapy of Tibetan medicine and carried out step treatment or comprehensive conditioning.To achieve three factors of balance,awakening and sleep in tune with the state.The article provides theoretical references to promote the standardization of the clinical diagnosis and treatment application of insomnia in Tibetan medicine and to promote the diversification of the insomnia treatment field.

Insomnia is an important problem facing the global public health field,presenting high morbidity and low treatment efficiency,while Tibetan medicine has rich clinical experience in treating insomnia,showing certain regional characteristics.The article adopts the method of documentary evidence to trace and analyse the diagnosis and treatment theories of Tibetan doctors on insomnia through the ages,It was found that due to three functional disorders,Bacon's inability to concentrate on the heart was the main pathogenesis of the disease,and divides into Tsh yer,Grng yer,and Gdon yer,three mainstream types of evidence.The treatment method adopted the traditional"quadruple"therapy of Tibetan medicine and carried out step treatment or comprehensive conditioning.To achieve three factors of balance,awakening and sleep in tune with the state.The article provides theoretical references to promote the standardization of the clinical diagnosis and treatment application of insomnia in Tibetan medicine and to promote the diversification of the insomnia treatment field.

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Triterpenes/pharmacology* ; Oxidative Stress ; Arthritis, Rheumatoid/genetics* ; Glutathione ; Superoxide Dismutase/metabolism* ; Glycosides/pharmacology* ; RNA, Messenger/metabolism*

Congenital diaphragmatic hernia consists of a defect in the embryonic development of the diaphragm that allows the passage of the abdominal viscera into the thoracic cavity, its diagnosis during pregnancy is quite rare. We present the case of a 31-year-old woman, with 23 weeks of gestation, who consulted for epigastric pain, nausea, and repetitive emetic episodes, without improvement with the medication provided. Due to the intense abdominal pain, a computed tomography of the abdomen and thorax was performed where the 28 mm defect was found at the left diaphragmatic level with protrusion of the gastric fundus to the thoracic cavity. She was taken to surgical management by laparoscopy with abdominal and thoracic approach, with a successful result and without maternal perinatal complications. Although the integrity of the diaphragmatic suture could be feared in relation to the increase in intraabdominal pressure due to uterine growth, the evolution of our patient and previous reports show that postoperative complications are not frequent. Successful vaginal delivery has even been described in some reports. Diaphragmatic hernias diagnosed during pregnancy are quite rare. We suggest that the optimal management of them during pregnancy is immediate surgical correction in case of persistent symptoms, more studies are needed to establish firm recommendations on the management of this pathology.

Congenital diaphragmatic hernia consists of a defect in the embryonic development of the diaphragm that allows the passage of the abdominal viscera into the thoracic cavity, its diagnosis during pregnancy is quite rare. We present the case of a 31-year-old woman, with 23 weeks of gestation, who consulted for epigastric pain, nausea, and repetitive emetic episodes, without improvement with the medication provided. Due to the intense abdominal pain, a computed tomography of the abdomen and thorax was performed where the 28 mm defect was found at the left diaphragmatic level with protrusion of the gastric fundus to the thoracic cavity. She was taken to surgical management by laparoscopy with abdominal and thoracic approach, with a successful result and without maternal perinatal complications. Although the integrity of the diaphragmatic suture could be feared in relation to the increase in intraabdominal pressure due to uterine growth, the evolution of our patient and previous reports show that postoperative complications are not frequent. Successful vaginal delivery has even been described in some reports. Diaphragmatic hernias diagnosed during pregnancy are quite rare. We suggest that the optimal management of them during pregnancy is immediate surgical correction in case of persistent symptoms, more studies are needed to establish firm recommendations on the management of this pathology.

Objective To investigate the feasibility of establishment of ultrasound radiomics-based models for classification of hepatic echinococcosis, so as to provide insights into precision ultrasound diagnosis of hepatic echinococcosis. Methods The ultrasonographic images were retrospectively collected from 200 patients with hepatic echinococcosis in Shiqu County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province in October 2014, and the regions of interest were plotted in ultrasonographic images of hepatic echinococcosis lesions. The ultrasound radiomics features of hepatic echinococcosis were extracted with 25 methods, and screened using pre-selection and the least absolute shrinkage and selection operator. Then, all ultrasonographic images were randomly assigned into the training and independent test sets according to the type of lesions at a ratio of 7:3. Machine learning models for classification of hepatic echinococcosis were created based on two classifiers, including kernel logistic regression (KLR) and medium Gaussian support vector machine (MGSVM). The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity and areas under the curves (AUC) of the created machine learning models for classification of hepatic echinococcosis were calculated. Results A total of 5 005 ultrasound radiomics features were extracted from 200 patients with hepatic echinococcosis using 25 methods, and 36 optimal radiomics features were screened through feature selection, based on which two machine learning models were created, including KLR and MGSVM. ROC curve analysis showed that MGS-VM presented a higher efficacy for hepatic echinococcosis classification than KLR in the training set, with a sensitivity of 0.82, a specificity of 0.78 and AUC of 0.88, while KLR presented a higher efficacy for hepatic echinococcosis classification than MGSVM in the independent test set, with a sensitivity of 0.82, a specificity of 0.72 and AUC of 0.86, respectively. Conclusions Ultrasound radiomics-based machine learning models are feasible for hepatic echinococcosis classification.

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-β1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.
Tandem Mass Spectrometry ; Molecular Docking Simulation ; Network Pharmacology ; Proto-Oncogene Proteins c-akt ; Papaveraceae ; Liver Cirrhosis ; Drugs, Chinese Herbal/pharmacology*

【Objective】To explore the role of lncRNA Xist in proliferation and migration of rat bone marrow mesenchymal stem cells（BMSC）and its possible mechanism.【Methods】BMSC were isolated，cultured and identified from the femur and tibia of 3 weeks old SD female rats in vitro. SiRNAs was designed and screened to acquire a high silencing efficiency siRNA. Lipo2000 was used to transfected si- Xist and si- NC into BMSC of the experimental group（si- Xist group）and the control group（si-NC group）. BMSC proliferation capacity was determined by CCK-8 assay. The transverse and longitudinal mobility of BMSC were measured by wound healing assay and transwell migration assays. QPCR was performed to verify the silencing efficiency of lncRNA Xist and detect the expression levels of SDF- 1 and CXCR4 mRNA. Western blot was used to quantify the expression of CXCR4 protein.【Results】The P3 generation BMSC shows shuttle- like or whirlpool-like，and flow cytometry showed CD11b（-），CD34（-），CD45（-），CD44（+），CD90（+），CD105（+）. When siRNAs were used to interfere with the expression of lncRNA Xist in BMSC ，the silencing efficiency of three siRNAs was 67.92% ，68.72% and 98.32% ，respectively. CCK- 8 assay showed that the OD450 value of si- Xist group decreased compared with si-NC group at 24 h and 48 h（P < 0.001，P < 0.01，respectively）and had no statistical difference at 12 h（P > 0.05）. Wound healing assay showed that the wound healing percentage of si-Xist group was lower than that of si-NC group（P < 0.05）；and the transwell migration assay showed that，compared with si- NC group，the cells that migrated through the polycarbonate membrane were obviously decreased at 6 h（P < 0.001）. QPCR experiment showed that CXCR4 expression in si-Xist group was lower than that in si-NC group at mRNA level（P < 0.05），while SDF-1 expression showed no significant statistical difference（P > 0.05）. Western blotting confirmed that CXCR4 expression in si- Xist group was lower than that in si-NC group（P < 0.05）.【Conclusions】LncRNA Xist promotes proliferation and migration of rat BMSC by regulating CXCR4 expression.

“Ro Nus ZhurJes” theory is the core content of Tibetan medicine property theory, and also the core compatibility law of Tibetan medicine. It takes six tastes of medicine as the surface medicinal property, three tastes after digestion by "three gastropyretie" as the inner medicinal property, eight properties and seventeen effects as the deep medicinal property, and its essential property is the special medicinal property, forming a multi-level medicinal property theory, but its internal structure still needs to be unified and sorted out, clinical practicability needs to be further improved. In this paper, literature mining, Tibetan medicine theory, vector structural model, K-means clustering analysis, Gephi 0.9.2 visualization and other methods were used to sort out the theory of Tibetan medicinal properties. It was found that the inherent structure of Tibetan medicine properties had the multi-dimensional structural characteristics of "seven medicinal properties+three characteristics", and that the same medicinal properties would overlap, while the opposite medicinal properties would offset and could be expressed by vectors. Therefore, the vector structural model of "Ro Nus ZhurJes" of Tibetan medicine was proposed in this paper. Taking twenty-five-flavor Yuganzi powder(skyu-ru-nyer-lnga) and 92 commonly used Tibetan medicine prescriptions as examples, the rates of single prescription with seventeen effects and multiple prescriptions acting on three factors were analyzed. The model analysis results were highly consistent with the clinical efficacy, and the main diseases were the same, which showed that this model had a high degree of fitting and interpretation. It could effectively and intuitively quantify the properties of Tibetan medicine prescriptions and uncover the complex hidden knowledge of Tibetan medicine theory. In the future, the vector structural model of "Ro Nus ZhurJes" will be applied to analyze the classical prescriptions of Tibetan medicine, and the fitting evaluation and modification optimization will be carried out continuously in order to improve the practicability of theory of Tibetan medicine property in the big data environment and provide methodological reference for the quantification of medicinal property of Tibetan medicine prescriptions.