Search

The blood proteome holds great promise for precision medicine but poses daunting challenges due to the low abundance of the majority of plasma proteins and the vast dynamic range across the proteome. We report the development and validation of a novel proteomic analysis technology – NUcleic acid Linked Immuno-Sandwich Assay (NULISA™) – that incorporates a dual capture and release mechanism to suppress the assay background to the minimum, thus drastically improving the signal-to-noise ratio. NULISA improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level, which is enabled by antibody-conjugated DNA sequences that mediate the purification of immunocomplexes and contain target-and sample-specific barcodes for next-generation sequencing-based, highly multiplexed analysis. To demonstrate its performance and utility, we developed a 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins that demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultra-high sensitivity enabled the detection of previously difficult-to-detect but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA uniquely addresses longstanding challenges in the proteomic analysis of liquid biopsy samples and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.

Purpose: To investigate the effects of Qijin granules on high glucose-induced proliferation and apoptosis in rat glomerular mesangial cells (MC).Methods: MC cells from rats were passaged and cultured, and randomly divided into control group (CNG), high glucose group (HGG), Western medicine group (WMG, high glucose + Benazepril + Gliquidone), and Qijin granules 1/2/3 group (high glucose + different doses of Qijin granules). Mesangial cells proliferation was measured using MTT assay. The NF-κB, MCP-1 and inflammatory factors in supernatant were determined by ELISA. Apoptosis rate and cell cycle were assessed by flow cytometry. The apoptosis-related TGF-β1/Smad signaling pathway-related protein expressions were measured by Western blot.Results: The A-value and early apoptosis rate, apoptosis rate and S-phase percentage, and protein expressions of NF-κB, MCP-1, IL-6, IL-2, TNF-ɑ, Bax, Cyt-C, caspase-3, TGF-β1, and p-Smad3 of MC cells in the HGG at 12 h, 24 h and 48 h were higher than those in the CNG. The above indices were lower in the WMG, and Qijin granules 1/2/3 groups than in the HGG. The Bcl-2, Smad7 protein expression level and the percentage of G1 and G2/M phase were lower in the HGG than in the CNG, and the above indeices were higher in the WMG and Qijin granules 1/2/3 group than in HGG.Conclusion: Qijin granules can dose-dependently inhibit high glucose-induced proliferation and apoptosis in rat MC cells, block the cell cycle and reduce inflammatory responses. This may be related to the regulation of NF-κB, MCP-1 and TGF-β1/Smad signaling pathways. These findings provide theoretical and experimental basis for the clinical treatment of early diabetic nephropathy.

Li Dai,* Xiangren Jin,* Liuxing Wang, Haibin Wang, Zhiqiang Yan, Guanghai Wang, Baichuang Liang, Fu Huang, Yuling Luo, Taichun Chen, Qian Wang Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Wang, Tel +8615885004333, Email Wangqian118@outlook.comAbstract: Currently, effective therapies for advanced gastric cancer with systemic metastasis are lacking. Pharmacological research has been slowly progressing over the past decades. Here, we report the case of a 56-year-old female with human epidermal growth factor receptor 2 (HER2) expression (IHC 2+/FISH-) in gastric cancer with systemic metastasis. The first-line therapeutic regime consisted of systemic administration of camrelizumab, local arterial infusion of oxaliplatin and arterial embolization, oral apatinib, and PS scheme (oral tegafur-gimeracil-oteracil (S-1) and paclitaxel (PTX), which was administered both intraperitoneally and systemically). After the treatment, a 3-month progression-free survival (PFS) was observed. Due to the occurrence of CTCAE grade 4 adverse reactions, the patient could not tolerate chemotherapy. In the second line of treatment, we replaced the PS scheme with disitamab vedotin and continued the use of carrilizumab and apatinib. After four cycles, efficacy evaluation showed that it was stable disease (SD), only CTCAE 1/2 grade adverse reactions occurred, and endoscopy examination showed local tumor control with a reduction in the ulcer lesion. At the time of submission of the current manuscript, a 6-month PFS was achieved and the treatment was continued. Due to the safety and efficacy of disitamab vedotin observed in our case, we propose that disitamab vedotin could be a promising drug for the treatment of advanced gastric cancer patients with HER2 expression.Keywords: gastric cancer, human epidermal growth factor receptor 2, disitamab vedotin

Objective To build a vomit-free ward of scientific and standardized management mode, and to evaluate its clinical effects on preventing nausea and vomiting in patients undergoing chemotherapy. Methods A total of 200 patients suffering from nausea and vomiting were randomly selected from the registration system, from which 120 cases were enrolled according to the inclusion and exclusion criteria. These subjects were divided into control group and observation group (60 patients in each). Both of the two groups received routine nursing care, while the treatment group subjects lived in the vomit-free wards where extra nursing interventions were applied to prevent chemotherapy-induced nausea and vomiting (CINV), with constant observation of the frequency and severity of nausea and vomiting. The outcomes of the subjects from both the groups as well as nurses’ cognition level of CINV were compared after four chemotherapy cycles. Results The difference in the scoring for the frequency and severity of nausea and vomiting in two groups was statistically significant (P < 0.05). The scores of nurses’ cognition level of CINV were compared between before and after the interventions, and the difference had statistical significance (P < 0.05). Conclusion The management mode aiming to build vomit-free wards could decrease the incidence of CINV in patients during chemotherapy, and at the same time increased the cognitive level of nursing staff toward CINV, which is of great value in clinical practice and is worthy of further application.