Nuclear emergency medical rescue is one of the important courses of military medical professional education, and improving the training level of nuclear emergency medical rescue plays a very important role in improving post competency of trainees. Based on the problem of disconnection between "teaching" and "need" in the occupational education of nuclear emergency medical rescue in the past, this study proposes the curriculum goal of "the combination of three abilities" and performs the optimization and practice of the occupational education curriculum system of nuclear emergency medical rescue from the aspects of curriculum setting, curriculum content, teaching methods, and assessment and evaluation. The results show that the new curriculum system can significantly improve the comprehensive ability of nuclear emergency medical rescue among trainees and better meet the requirements for their posts, thereby playing an important role in cultivating high-quality military medical talents in nuclear emergency medical rescue.

Aim To investigate the effect of discoidin domain receptor 1(DDR1)on high glucose induced endothelial cell dysfunction and the underlying mecha-nism.Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided in-to the control group and high glucose induction group(HG).HUVECs were treated with 33 mmol·L-1 D-glucose for 48 hours to construct endothelial dysfunc-tion.Pyroptosis was detected using propidium iodide staining(PI);lactate dehydrogenase(LDH)and IL-1β,IL-18 levels were determined using enzyme linked immunosorbent assay(ELISA);the expression of DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related proteinses were detected using Western blot.Subsequently,the experiment was divid-ed into the control group,HG group,HG+DDR1 NC group,and HG+DDR1 siRNA group.The effect of high glucose on the proliferation and migration of HU-VECs was observed after transfection with DDR1 siR-NA for 24 hours;ELISA was used to detect the endo-thelial nitric oxide synthase(eNOS),vascular cell ad-hesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),as well as LDH,IL-1β,IL-18 levels;PI was employed to detect pyroptosis;Western blot was applied to detect DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related pro-teins.Results Compared with the control group,HG group decreased eNOS content,increased VCAM-1 and ICAM-1 contents,decreased cell viability and migration ability,and significantly increased the expressions of DDR1,p-NF-κB,NLRP3 and pyroptosis related pro-teins.The levels of LDH,IL-1β,IL-18 and the rate of pyroptosis significantly increased(P＜0.05).Com-pared with HG group,DDR1 siRNA could promote the secretion of eNOS,decrease the levels of VCAM-1,ICAM-1,LDH,IL-1β and IL-1 8,increase cell viability and migration ability,reduce the expression of p-NF-κB,NLRP3 and pyroptosis related proteins,and inhibit high glucose-induced pyroptosis of HUVECs(P＜0.05).Conclusions Gene silencing DDR1 can im-prove vascular endothelial cell dysfunction induced by high glucose,and the mechanism is related to the inhi-bition of NF-κB/NLRP3 signaling pathway mediated pyroptosis.

【Objective】 To explore the composition of culturable bacteria in platelets through bacterial culturomics and verify the results of culturomics and metagenomics to improve the detection rate of bacteria in platelets. 【Methods】 Platelet samples from 6 healthy people were collected. Eight kinds of culture media were placed in aerobic conditions and 12 kinds of culture media were placed in anaerobic conditions for large-scale culture and isolation of bacteria in platelets. The isolated single colony was identified by 16S rRNA gene sequencing. The bacterial abundance of healthy human platelet microbiome was analyzed by metagenomic sequencing, and the cultivable bacterial species in platelets was confirmed based on metagenomic and culturomics results. 【Results】 A total of 90 strains of bacteria belonging to 3 phylums, 5 classes, 5 orders, 7 families, 9 genus and 23 species were isolated from 6 platelet samples by culturomics. Among them, the strains with more monoclonal clones at the species level were Brevundimonas aurantiaca (16.7%), Bacillus sp. Y1 (15.6%), Cutibacterium acnes (14.4%) and Brevibacillus brevis (13.3%). The platelet samples sequenced by mNGS showed that the abundance values of Proteobacteria, Firmicutes and Actinobacteria were high. The bacteria detected by both culturomics and metagenomic sequencing methods were as follows: Firmicutes: Bacillus sp. Y1, B. thuringiensis, B. cereus, B. mobilis, B. velezensis, Staphylococcus epidermidis, and Brevibacillus brevis; Actinobacteria: Cutibacterium acnes; Proteobacteria: Escherichia coli and Delftia tsuruhatensis. 【Conclusion】 The mutual validation of culturomics and metagenomics has identified some bacteria, proving that bacteria exist in platelets.

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.
Humans ; Castleman Disease/pathology* ; Plasma Cells/pathology* ; Immunoglobulin G4-Related Disease ; China ; Lymphadenopathy/pathology* ; Inflammation/pathology* ; Lymph Nodes/pathology* ; Diagnosis, Differential ; Lymphadenitis/pathology* ; Immunoglobulin G/metabolism*

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

ObjectiveThrough the visual analysis of animal experimental literature on Traditional Chinese Medicine (TCM) nursing technology, the relevant research hot spots were condensed and the research trends of relevant animal models were discussed, to provide reference for subsequent research. MethodsThe literature related to animal experiments on Chinese medicine nursing technology was retrieved from Wan Fang database, Chinese Science and Technology Journal Database (VIP), China National Knowledge Infrastructure Engineering Database (CNKI), China Biomedical Literature Database (CBM), PubMed and Web of Science until June 30, 2022. Visual analysis was performed using VOSviewer 1.6.17 software. ResultsA total of 1 864 articles in Chinese and 126 articles in English were included, with the number of annual publications increasing year by year. The relevant literature involved 18 TCM nursing techniques, with the largest number (426) involving massage having the highest number of articles. It involved 4 496 authors, out of whom 358 were core authors accounting for 7.9% of all authors, and had a total count of 3 706 keywords forming 7 clusters. The research hotspots mainly included massage treatment of inflammatory diseases and analgesic effect, acupoint injection treatment of allergic rhinitis and myocardial ischemia, acupoint application treatment of asthma-related respiratory diseases, and moxibustion treatment of inflammatory diseases. The study of the mechanism of abdominal massage on insulin resistance is the latest research topic among them. ConclusionIn recent years, the animal model of abdominal massage has gained increasing popularity in animal experiments of TCM nursing techniques. However, the establishment and application of animal models related to Chinese medicine soaking and Chinese medicine hot ironing have not yet received attention. This area can be explored in the future to further improve the animal experimental research on Chinese medicine nursing technology.

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.
Animals ; Flavonoids ; Inflammation/genetics* ; Interferon-gamma ; Lipopolysaccharides/adverse effects* ; Mice ; NF-kappa B/metabolism* ; Toll-Like Receptor 4/metabolism*

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate