Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

In order to achieve rapid proliferation and adapt to the complex microenvironment, tumor cells have dominant characteristics such as unique metabolic patterns and the ability to escape from immunoregulation. Tumor cells reprogram multiple metabolic pathways to promote immune escape, which impacts tumor diagnosis, treatment and prognosis. Based on the effect of metabolic changes on tumor immune escape and its molecular mechanism, metabolic regulation provides new approaches to enhance immunotherapy. We review recent advances in tumor immuno-escape and immunotherapy based on metabolic regulation. Cutting-edge analytical techniques and methods for tumor metabolism research such as metabolomics, mass spectrometry imaging-based spatially-resolved metabolomics and metabolic flow analysis are also discussed.

Objective To explore the effects of magnesium sulfate in combination with astragalus membranaceus injection on the birth outcomes and expression of placenta tissue related gene of patients with gestational hypertension. Methods Seventy-six gestational hypertension patients were selected and randomly assigned to control group (n = 38) and treatment group (n = 38). The control group was given intravenous injection of 25％ magnesium sulfate (60 mL) once daily for 7 days,while the treatment group was give intravenous injection of astragalus (60 mL) on the basis of the control group once daily for 7 days. The changes of blood pressure,mean arterial pressure (MAP) and 24 h urine protein content of the two groups were compared. The placenta tissue of the two groups were collected after childbirth. Results After treatment,the total effective rates of the control group and the treatment group were86. 84％ (33/38) and 97. 37％ (37/38) ,respectively; the difference was statistically significant (P < 0. 05). There were significant differences between the control group and the treatment group in systolic blood pressure [(147. 21 ± 20. 01) mmHg vs (128. 46 ± 18. 43) mmHg],diastolic blood pressure [(90. 25 ± 15. 46) mmHg vs (73. 14 ± 14. 53) mmHg],MAP [(126. 76 ± 9. 65) mmHg vs (108. 15 ± 9. 57) mmHg] and the 24 h urine protein content [(2. 65 ±0. 87) g vs (1. 34 ±0. 79) g](P < 0. 05). Conclusion Magnesium sulfate combined with astragalus membranaceus injection can reduce the blood pressure of gestational hypertension patients,improve the pregnancy outcome; the action mechanism maybe related to the up-regulation of PLGF and MMP-9 protein expression of placenta tissue.

Objective To investigate the effect of puerarin on oxidative stress and immune status in placenta of preeclampsia (PE) rats. Methods Forty-five pregnant female SD rats were randomly divided into control group,model group and test group,15 rats in each group. The rats in model group and test group were subcutaneously injected with 100 mg·kg-1 of L-arginine methyl ester (L-NAME) once daily from Day 13-21 of gestation,the rats in control group were injected with the same amount of saline; and the rats in test group were intraperitoneally injected with 80 mg·kg-1 of puerarin solution once daily from Day 17-21 of gestation,control group and model group were injected with the same amount of 0. 9％ NaCl. The caudal arterial pressure and 24 h urinary protein content were measured at Day 10,16 and 21 of gestation,the oxidative stress indexes in rat placenta was detected by thibabituric acid method and Xanthine oxidase method,the cellular immune function was detected by flow cytometry,and the X-linked inhibitor of apoptosis protein (XIAP) expressionin of rat placenta trophoblasts was detected by Western blot. Results On Day 21 of gestation,there were significant differences between the model group and the control/test group in caudal arterial pressure [(136. 25 ± 5. 48) mm- Hg vs (119. 25 ± 4. 21) mmHg or (123. 52 ± 6. 45) mmHg],24 h-urinary protein contents [((11. 83 ± 0. 12) mg vs 6. 42 ± 0. 08) mg or (8. 58 ± 0. 12) mg],the content of MDA in placenta tissue [(4. 75 ± 0. 08) mmol·mg-1 vs(10. 69 ± 0. 07) mmol·mg-1,(8. 37 ± 0. 08) mmol·mg-1 ],the content of SOD [(93. 26 ± 4. 29) U·mg-1 vs(168. 97 ± 3. 42) U·mg-1 or (112. 63 ± 3. 48) U·mg-1 ],the ratio of CD4 +/CD8 + [(2. 61 ± 0. 56) vs(1. 46 ± 0. 05) or (1. 48 ± 0. 12) ] and the relative expression of XIAP protein in trophoblast [(0. 89 ± 0. 05) vs(0. 36 ± 0. 09) or (0. 41 ± 0. 11) ](all P < 0. 05). Conclusion Puerarin can inhibit the oxidative stress reaction and enhance the cellular immune function in the placenta of PE rats,and reduce the expression of XIAP protein in the placenta tissue trophoblasts to reduce the apoptosis of placenta trophoblasts.

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. Trial Registration Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.
Adult ; China ; Cross-Over Studies ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Peritoneal Dialysis ; adverse effects ; instrumentation ; methods ; Quality of Life ; Temperature

BACKGROUNDCleidocranial dysplasia (CCD) is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 (RUNX2). Here, we report a sporadic Chinese case presenting typical symptoms of CCD.

METHODSWe made genetic testing on this sporadic Chinese case and identified a novel RUNX2 frameshift mutation: c.1111dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2.

RESULTSRUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated.

CONCLUSIONSWe identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.

Adolescent ; Cell Nucleus ; metabolism ; Cleidocranial Dysplasia ; genetics ; Core Binding Factor Alpha 1 Subunit ; genetics ; Female ; Frameshift Mutation ; genetics ; Humans ; Microscopy, Fluorescence ; Mutation