New-Onset Fulminant Type 1 Diabetes Following SARS-CoV-2 Protein Subunit Vaccine: A Case Report and Literature Review

The ravages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide have sped up the development of relevant vaccines, which is accompanied by public concerns over possible adverse effects. We report a rare case of a 39-year-old woman who suffered from severe hyperglycemia and ketoacidosis with normal hemoglobin A1c four days after SARS-CoV-2 protein subunit vaccine, which is consistent with the diagnosis of fulminant type 1 diabetes (FT1D). She received insulin therapy and recovered after 24 days from onset of the symptoms. This is the first case of new-onset FT1D after SARS-CoV-2 protein subunit vaccination and one of only six that developed after any form of SARS-CoV-2 vaccination.We hope to raise awareness of this potential adverse consequence and recommend careful monitoring after vaccination in patients even without a medical history of diabetes.

Estimates of influenza-associated excess mortality by three regression models in Shanxi Province during 2013-2017 / 中华预防医学杂志

Objective@#Using three models too estimate excess mortality associated with influenza of Shanxi Province during 2013-2017.@*Methods@#Mortality data and influenza surveillance data of 11 cities of Shanxi Province from the 2013-2014 through 2016-2017 were used to estimate influenza-associated all cause deaths, circulatory and respiratory deaths and respiratory deaths. Three models were used: (i) Serfling regression, (ii)Poisson regression, (iii)General line model.@*Results@#The total reported death cases of all cause were 157 733, annual death cases of all cause were 39 433, among these cases, male cases 93 831 (59.50%), cases above 65 years old 123 931 (78.57%). Annual influenza-associated excess mortality, for all causes, circulatory and respiratory deaths, respiratory deaths were 8.62 deaths per 100 000, 6.33 deaths per 100 000 and 0.68 deaths per 100 000 estimated by Serfling model, respectively; and 21.30 deaths per 100 000, 16.89 deaths per 100 000 and 2.14 deaths per 100 000 estimated by General line model, respectively; and 21.76 deaths per 100 000, 17.03 deaths per 100 000 and 2.05 deaths per 100 000, estimated by Poisson model, respectively. Influenza-related excess mortality was higher in people over 75 years old; influenza-associated excess mortalityfor all causes, circulatory and respiratory deaths, respiratory deaths were 259.67 deaths per 100 000, 229.90 deaths per 100 000 and 32.63 deaths per 100 000, estimated by GLM model, respectively; and 269.49 deaths per 100 000, 233.69 deaths per 100 000 and 31.27 deaths per 100 000, estimated by Poisson model,respectively.@*Conclusion@#Excess mortality associated with influenza mainly caused by A (H3N2), Influenza caused the most associated death amongold people.

GLU4-may increase insulin sensitivity in type 2 diabetic rats / 中国医师杂志

Objective To investigate effect of berberine on fasting glucose , fasting serum insulin, islet morphology, and ex-pression of glucose transporter 4 (GLU-4) of islet in type 2 diabetes mellitus (T2DM) rats.The present study aimed to evaluate the ually, especially for high-dose group ( P <0.01).⑷Compared with normal group , INS of diabetic control group was significantly de-creased ( P <0.05), INS of low-dose, middle-dose, and high-dose groups were all increased gradually , especially for high-dose group ( P <0.01 ) .Conclusions Berberine has the effects of antidiabetes via ameliorate insulin sensitivity , and promotes GLUT-4 protein expression .

Influence of nursing procedures on pressure sore during the operation on brain tumor / 现代临床护理

Objective To explore the effect of nursing procedure on pressure sore in patients with brain tumor.Methods The nursing procedures were used in the nursing of 86 brain tumor patients.The procedures included assessment of pressure ulcer risk factors and regulations of nursing objective and the measures for preventing pressure ulcer.Result None of the patients contracted pressure ulcer during operation.Conclusion The nursing procedures for brain tumor patients can enable the nurses to plan nursing activities for specific purpose,avoid the occurrence of pressure sore and thus improve the quality of nursing.

Jα33+ MAIT cells play a protective role in TNBS induced intestinal inflammation.

BACKGROUND/AIMS: Mucosa-associated T-lymphocyte (MAIT) cells that are selectively accumulated in the intestinal mucosa may be involved in immune regulation. MAIT cells are determined by their Vα7.2-Jα33 (human)/Vα19-Jα33 (mice) invariant chain. The encoding DNA sequences of Human Jα33 and mouse Jα33 are identical. In order to study the role of MAIT cells in IBD we produced anti-Jα33 antibody to detect MAIT cells in TNBS induced IBD models. METHODOLOGY: Colitis was induced by TNBS in male BALB/c mice. Jα33+MAIT cells from normal mice were transferred into TNBS induced mice as donors. Colitis severity was evaluated clinically and histologically, under the condition of transferred Jα33+MAIT cells. RESULTS: The mRNA and protein expression levels of MAIT aTCR in the colonic mucosa were decreased after TNBS administration; Jα33+MAIT cells were aggregated in spleen after TNBS administration. The disease activity index (DAI) which was determined by weight loss, stool consistency and intestinal bleeding, increased after TNBS administration. Transferred Jα33+MAIT cells significantly degrade the increase in the disease activity index scores. CONCLUSIONS: Taken together, the results indicated that the aggregation of Jα33+MAIT cells in intestinal mucosa improved TNBS-induced colitis. We conclude that Jα33+MAIT cells play a protective role in TNBS induced intestinal inflammation.

Effect of recombinant human connective tissue growth factor on the expression of membrane type-1 matrix metalloproteinase and matrix metalloproteinase 2 in human osteoblasts / 中华内分泌代谢杂志

Human osteoblast was treated with recombinant human connective tissue growth factor (rCTGF). This experiment showed that rCTGF increased membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 protein expression in a dose- and time-depentent manner in human osteoblasts. rCTGF induced activation of p38 MAPK in human osteoblasts. p38 MAPK inhibitor SB23058 abrogated the effect of rCTGF on the expressions of membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 in human osteoblasts.

Effects of recombinant human connective tissue growth factor on the expression of osteoprotegerin and receptor activator of NF-κB ligand in human osteoblasts / 中华内分泌代谢杂志

Objective To investigate the effects of recombinant human connective tissue growth factor (rCTGF) on the expression of osteoprotegerin (OPG) and RANKL ( receptor activator of NF-κB ligand ) in human osteoblasts, as well as the mechanisms involved. Methods Human osteoblasts were treated with rCTGF. The expressions of OPG and RANKL were assessed by Western blotting. The expressions of focal adhesion kinase ( FAK), mitogen-activated protein kinase (MAPK) were also observed. Results rCTGF inhibited RANKL protein expression in a dose-and time-depentent manner in human osteoblasts, while the expression of OPG kept unchanged. rCTGF induced activation of p38MAPK and dephosphorylation of FAK in human osteoblasts, but had no effect on ERK and JNK phosphorylation. p38MAPK inhibitor SB23058 abrogated the inhibitory effect of rCTGF on RANKL in human osteoblasts. Conclusion rCTGF inhibits the expression of RANKL in human osteoblasts via activation of p38MAPK and dephosphorylation of FAK.

EBV-induced human CD8+ NKT cells suppress tumorigenesis by EBV-associated malignancies.

The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8(+) NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8(+) NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-gamma-biased CD8(+) NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4-biased CD4(+) NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induced CD8(+) NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8(+) NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4(+) NKT cells are synergetic with CD8(+) NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD8(+) NKT cells could be a useful strategy in management of EBV-associated malignancies.

CD19+CD5+ B cells in primary IgA nephropathy.

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.

Effect of cyclic mechanical stimulation on expression of connective tissue growth factor in MG63 osteoblast-like cells / 中华内分泌代谢杂志

Objective To investigate cyclic mechanical stimulation on expression of connective tissue growth factor (CTGF) in osteoblast-like cells (MG63) and to explore the rote of MAPK involved in the process.Methods Expressions of CTGF protein and mRNA in MG63 cells were detected by Western blot and RT-PCR,respectively. Phosphorylation levels of p38, ERK, JNK were examined by Western blot. Results Cyclic mechanical stimulation upregulated expressions of CTGF protein and mRNA. The levels reached a maximal response of 2-3 fold after 3-6 h. ERK and JNK signal pathways were activated by cyclic mechanical stimulation, the phosphorylated proteins increased within 10 min of stretch, phosphorylated ERK reached maximal levels by 60 min of stretch, phosphorylated JNK reached maximal levels by 15-30 min of stretch, but not for p38 signal pathway.Only the inhibitior of JNK signal pathway (SP600125) markedly suppressed stretch-induced CTGF expression,meanwhile the inhibitors of ERK (PD98059) and p38 (SB203580) did not show such effect. Conclusion Cyclic mechanical stimulation upregulates CTGF expression via JNK-dependent pathway in MG63 cells.

Effects of recombinant human connective tissue growth factor on proliferation, differentiation, and apoptosis in human osteoblasts / 中华内分泌代谢杂志

Objective To investigate the effects of recombinant human connective tissue growth factor (rCTGF) on the proliferation, differentiation and apoptosis in human osteoblasts. Methods Human osteoblasts were treated with rCTGF, cell proliferation was measured by [3 H] -thymidine ([3 H] -TdR) incorporation method,the activity of alkaline phosphatase (ALP) was determined using α-nitrophenyl phosphate as a substrate, the expression of type Ⅰ collagen was determined by Western blotting, osteocalcin in conditioned media was measured by radioimmune assay, and cell apoptosis was assayed by flow cytometry. Results rCTGF promoted proliferation and differentiation of human osteoblasts in a dose-depentent manner, rCTGF increased ALP activity, osteocalcin and type I collagen secretion in a dose-depentent manner, rCTGF inhibited human osteoblastic apoptosis induced by serum deprivation. Conclusion rCTGF can promote osteoblastic proliferation, and differentiation and protect osteoblast against apoptosis, suggesting that CTGF plays an essential role in bone metabolism.

CCL19 and CXCL13 synergistically regulate interaction between B cell acute lymphocytic leukemia CD23+CD5+ B Cells and CD8+ T cells.

Interacting with T cells, cytokine-producing B cells play a critical protective role in autoimmune diseases. However, the interaction between malignant B and T cells remains to be fully elucidated. In a previous study, we have reported that ligation of CCL19-CCR7 and CXCL13-CXCR5 activates paternally expressed gene 10 (PEG10), resulting in an enhancement of apoptotic resistance in B-cell acute lymphocytic leukemia (B-ALL) CD23+CD5+ B cells. Here, we report that B-ALL CD23+CD5+ B cells produce IL-10 at high level, which can be further elevated by costimulation with CCL19 and CXCL13. CCL19/CXCL13-activated B-ALL CD23+CD5+ B cells, in turn, increase IL-10 expression in syngeneic CD8+ T cells in a B cell-derived IL-10-dependent manner and requiring a cell-cell contact. IL-10 secreted from B-ALL CD23+CD5+ B cells in vitro impairs tumor-specific CTL responses of syngeneic CD8+ T cells. The impairment of cytotoxicity of syngeneic CD8+ T cells is escalated by means of CCL19/CXCL13-induced up-regulation of IL-10 from B-ALL CD23+CD5+ B cells. Moreover, using a short hairpin RNA to knockdown PEG10, we provide direct evidence that increased expression of PEG10 in B-ALL CD23+CD5+ B cells is involved in malignant B-T cell interaction, contributing to the up-regulation of IL-10 expression, as well as to the impairment of cytotoxicity of syngeneic CD8+ T cells. Thus, malignant B-ALL CD23+CD5+ B cells play an immunoregulatory role in controlling different inflammatory cytokine expressions. IL-10 may be one of the critical cellular factors conferring B-ALL CD23+CD5+ B cells to escape from host immune surveillance.

CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+CD5+ B cells.

CXCL13/CXCR5 and CCL19/CCR7 play a quite important role in normal physiological conditions, but the functions of both chemokine/receptor pairs in pathophysiological events are not well-investigated. We have investigated expression and functions of CXCL13/CXCR5 and CCL19/CCR7 in CD23+CD5+ and CD23+CD5- B cells from cord blood (CB) and patients with B cell lineage acute or chronic lymphocytic leukemia (B-ALL or B-CLL). CXCR5 and CCR7 are selectively expressed on B-ALL, B-CLL, and CB CD23+CD5+ B cells at high frequency, but not on CD23+CD5- B cells. Although no significant chemotactic responsiveness was observed, CXCL13 and CCL19 cooperatively induce significant resistance to TNF-alpha-mediated apoptosis in B-ALL and B-CLL CD23+CD5+ B cells, but not in the cells from CB. B-ALL and B-CLL CD23+CD5+ B cells express elevated levels of paternally expressed gene 10 (PEG10). CXCL13 and CCL19 together significantly up-regulate PEG10 expression in the same cells. We have found that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulate PEG10 expression and function, subsequently stabilize caspase-3 and caspase-8 in B-ALL and B-CLL CD23+CD5+ B cells, and further rescue the cells from TNF-alpha-mediated apoptosis. Therefore, we suggest that normal lymphocytes, especially naive B and T cells, use CXCL13/CXCR5 and CCL19/CCR7 for migration, homing, maturation, and cell homeostasis as well as secondary lymphoid tissues organogenesis. In addition, certain malignant cells take advantages of CXCL13/CXCR5 and CCL19/CCR7 for infiltration, resistance to apoptosis, and inappropriate proliferation.

All roads lead to Rome: pathways of NKT cells promoting asthma.

NKT cells are the prominent manipulator in asthma development. Asthmatic NKT cells migrate from thymus, spleen, liver and bone marrow into blood vessels, and then concentrate in airway bronchi mucosa. This recruitment is dependent on high expression of CCR9 and engagement of CCL25/CCR9. NKT cells promote asthma in two different pathways. One is an indirect pathway. NKT cells contact with CD3(+) T cells and induce them secreting large quantity of Th2 cytokines (IL-4, IL-13), which requires the participation of dentritic cells and the synergic signaling of CCL25/CCR9 and CD226. The other is a direct pathway. Circulating asthmatic NKT cells selectively highly express Th1 cytokines (IFN-gamma). Once reached airway epithelium, most NKT cells shift to Th2-bias, highly expressing IL-4, IL-13, but not IFN-gamma. Both pathways lead to airway hyperresponsiveness and inflammation, asthma development. Comparing to the well documented suppressive regulatory T cells, CD4(+)CD25(+) T cells, NKT cells perform as a novel active regulator in asthma. These recent understanding of NKT cells performance in the development of asthma might unveil new therapy targets and management strategies for asthma.

Different neurotropic pathogens elicit neurotoxic CCR9- or neurosupportive CXCR3-expressing microglia.

What mechanism that determines microglia accomplishing destructive or constructive role in CNS remains nebulous. We report here that intracranial priming and rechallenging with Toxoplasma gondii in mice elicit neurotoxic CCR9+ Irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis and produce a high level of TNF-alpha; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive CXCR3+ Irg1- microglia, which are sensitive to apoptosis and produce a high level of IL-10 and TGF-beta. Administration of CCR9 and/or Irg1 small interfering RNA alters the frequency and functional profiles of neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- microglia in vivo. Moreover, by using a series of different neurotropic pathogens, including intracellular parasites, chronic virus, bacteria, toxic substances, and CNS injury to intracranially prime and subsequent rechallenge mice, the bi-directional elicitation of microglia has been confirmed as neurotoxic CCR9+ Irg1+ and neurosupportive CXCR3+ Irg1- cells in these mouse models. These data suggest that there exist two different types of microglia, providing with a novel insight into microglial involvement in neurodegenerative and neuroinflammatory pathogenesis such as Alzheimer's disease and AIDS dementia.

V alpha 24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement.

We have demonstrated that Valpha24(+)Vbeta11(+) invariant (Valpha24(+)i) NKT cells from patients with allergic asthma express CCR9 at high frequency. CCR9 ligand CCL25 induces chemotaxis of asthmatic Valpha24(+)i NKT cells but not the normal cells. A large number of CCR9-positive Valpha24(+)i NKT cells are found in asthmatic bronchi mucosa, where high levels of Th2 cytokines are detected. Asthmatic Valpha24(+)i NKT cells, themselves Th1 biased, induce CD3(+) T cells into an expression of Th2 cytokines (IL-4 and IL-13) in cell-cell contact manner in vitro. CD226 are overexpressed on asthmatic Valpha24(+)i NKT cells. CCL25/CCR9 ligation causes directly phosphorylation of CD226, indicating that CCL25/CCR9 signals can cross-talk with CD226 signals to activate Valpha24(+)i NKT cells. Prestimulation with immobilized CD226 mAb does not change ability of asthmatic Valpha24(+)i NKT cells to induce Th2-cytokine production, whereas soluble CD226 mAb or short hairpin RNA of CD226 inhibits Valpha24(+)i NKT cells to induce Th2-cytokine production by CD3(+) T cells, indicating that CD226 engagement is necessary for Valpha24(+)i NKT cells to induce Th2 bias of CD3(+) T cells. Our results are providing with direct evidence that aberration of CCR9 expression on asthmatic Valpha24(+)i NKT cells. CCL25 is first time shown promoting the recruitment of CCR9-expressing Valpha24(+)i NKT cells into the lung to promote other T cells to produce Th2 cytokines to establish and develop allergic asthma. Our findings provide evidence that abnormal asthmatic Valpha24(+)i NKT cells induce systemically and locally a Th2 bias in T cells that is at least partially critical for the pathogenesis of allergic asthma.

The changes of functions of chemokine receptor 9 on T cell lymphocytic leukemia patients / 中国免疫学杂志

Objective:To observe the influences of functions of chemokine receptor 9(CCR9) on leukemia patients,we analyzed 38 typical T cell lymphocytic leukemia cases.Methods:The functions of T ALL and T CLL CD4+T cells towards TECK/CCL25 were determined by chemotaxis assay and adhesion assay.Results:Almost in all of the T ALL patients,TECK/CCL25(a ligand for CCR9)could induce a high chemotactic migration of T ALL CD4+ cells as well as a high adhesion.Conclusion:It indicates that CCR9 and its ligands may promote survival or proliferation of T ALL cells. [

CCR7~+CD8~+CD45RO~+ T Cells induced Differentiation of CD4~+T Cells to Th2 Cells in Active Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To determine the functions of CCR7+CD8+CD45RO+ T cells on CD4+T cells in systemic lupus erythematosu(SLE).Methods The expres sion of cytokines in CD4+T cells was measured by flow cytometry,real-time qua ntitative reverse transcription polymerase chain reaction and Northern blotting.A chemotaxis assay was used to detect their functions.Results In the case of active SLE,CCR7+CD8+CD45RO+T cells could induce CD4+T cells to express high le vels of Th2-cytokine (IL-4),and low levels of Tr1-cytokines (IL-10 and TGF-?),than those in normal controls and inactive SLE (P

Utilization of Anticoagulant Drugs in Our Hospital During 2004～2007 / 中国药房

OBJECTIVE:To probe into the status quo and tendency of the utilization of anticoagulant drugs in our hospital. METHODS:The utilization of anticoagulant drugs in our hospital from 2004 to 2007 were analyzed statistically with regard to drug varieties,consumption quantity and consumption sum as well as DDDs. RESULTS:The consumption sum of anticoagulant drugs in our hospital increased year by year. Of all the anticoagulant drugs,leading the list in terms of consumption sum were ozagrel,low molecular heparin calcium and clopidogrel. CONCLUSION:The utilization of anticoagulant drugs in our hospital is basically in line with the current medication principle of anticoagulant drugs and the general medication trend both at home and abroad.