BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

Objective To investigate the effect of vonoprazan fumarate on serum inflammatory factors in patients with reflux esophagitis.Methods Eighty patients with reflux esophagitis who were admitted to the Suzhou 100 Hospital from May 2021 to March 2023 were enrolled and divided into observation group(treated with vonoprazan fumarate,n=40)and control group(treated with omeprazole,n=40)according to the random number table method.The treatment efficacy,adverse reactions,Gastroesophageal Reflux Disease Questionnaire(GERDQ)score,gastrointestinal symptom score(GIS),serum gastrin(GAS),vasoactive intestinal peptide(VIP),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and the recurrence within 6 months after treatment were compared between the two groups.Results The total effective rate of the observation group was higher than that of the control group(P<0.05).GERDQ score and GIS after treatment were lower than those before treatment in both groups,and the GERDQ score and GIS after treatment in the observation group were lower than those in the control group(all P<0.05).GAS after treatment was higher than that before treatment in both groups,and GAS after treatment in the observation group was significantly higher than that in the control group(all P<0.05).VIP,TNF-α,IL-6 and IL-8 after treatment were significantly lower than those before treatment in both groups,and after treatment these parameters in the observation group were significantly lower than those in the control group(all P<0.05).There was no significant difference in the total incidence of adverse reactions between the two groups(P>0.05).No patients were lost during follow up.The recurrence rate was 2.50%(1/40)in the observation group and 7.50%(3/40)in the control group(χ2=0.263,P=0.608).Conclusion In treating reflux esophagitis with vonoprazan fumarate,the pharyngeal reflux,gastrointestinal hormones,and serum inflammatory factor levels can be improved,and the long-term efficacy is satisfactory.

Objective To establish a viable bacteria assay for Helicobacter pylori(H.pylori)by assessing the cgt gene expression,and to develop accordingly a rapid and novel testing method for clinical precision treatment.Methods Viable bacteria count was determined in bacterial cultures.The transcriptional expression level of cgt(hp0421),the conserved gene that encodes cholesterol-α-glucosyltransferase(CGT)in H.pylori,was measured by RT-PCR.The correlation between the number of colonies and cgt gene transcription expression was analyzed and the regression model was constructed.The linear range,sensitivity,and specificity of the new method were examined accordingly.The bactericidal action of clarithromycin was assessed using this method to verify the performance of the method in determining clinical bacterial drug resistance.Results The Ct values of cgt for H.pylori colony counts of 102,104,106,and 108 CFU/mL were 29.67±0.14,23.37±0.36,17.65±0.37,and 11.38±0.39,respectively.In the range of 101-108 CFU/mL,the regression equation for cgt gene expression and viable bacterial counts determined by RT-qPCR was y=-0.350 1x+12.49,with the correlation coefficient being R2=0.9992 and the sensitivity being 101 CFU/mL,showing no cross-reaction with 13 other bacteria.The lg values of live H.pylori bacteria treated with clarithromycin at 0,5,10,20,and 40 μg/mL for 12 h were 2.57±0.02,2.45±0.01,2.19±0.02,1.91±0.07,and 1.33±0.05,respectively.The corresponding cgt gene Ct values were 27.76±0.09,28.37±0.24,29.51±0.14,30.11±0.12,and 31.66±0.11.By applying the cgt gene expression in the equation,the estimated counts of viable bacteria were found to be 2.73±0.03,2.52±0.08,2.11±0.05,1.89±0.02,and 1.33±0.04,showing no significant difference in statistical analysis(P＞0.05).Conclusion The method for assessing viable bacteria account by evaluating cgt gene expression in H.pylori was successfully established,significantly reducing the time required to determine viable bacteria count and providing a new method for clinical viable bacteria testing.

Objective · To explored the correlation of preoperative peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) with clinical characteristics and prognosis of ovarian cancer. Methods · Patients' clinicopathological data of 127 cases of benign tumors and 286 cases of malignant tumor were collected, and the correlation between the level NLR and PLR in patients with ovarian cancer clinical pathology indicators and overall survival was analyzed. Results · preoperative NLR and PLR levels in patients with ovarian cancer were higher than those in benign tumors(P=0.000). The optimal cut-off point of NLR and PLR were 3.0 and 151. There was statistical significant difference between the high level of NLR group (NLR ≥ 3) and the low level of NLR group in pathological type, FIGO staging, lymph node metastasis, CA125 level and the amount of ascites (P<0.05). There was statistical significant difference between the high level of PLR group (PLR ≥ 151) and the low level of PLR group in FIGO stage,transfer status, CA125 level and quantity of ascites (P<0.05). The median survival time for NLR/PLR in the high level group were 33 and 33.5 months lower than that ofthe corresponding group of 44.5 and 49.5 months (P=0.044, P=0.000). Multivariate Cox regression analysis showed that PLR ≥ 151 were independent risk factors affectOS in ovarian cancer patients (HR=1.936, 95% CI=1.013-3.698, P=0.045). Conclusion · The elevated blood preoperative PLR indicates poor prognosis of ovarian cancer patients. Preoperative PLR may serve as an important independent prognostic factor for ovarian cancer patients.

Objective To investigate the clinical pathological characteristics, diagnosis and treatment of breast rhabdomyosarcoma, and to enhance the awareness of malignancy infiltration to bone marrow (BM). Methods The data of one case of Rhabdomyosarcoma of breast were analyzed retrospectively. BM aspirate and biopsy, morphology, immunology, cytogenetics, molecular biology (MICM) in different parts of BM, peripheral blood smear, fine puncture of breast mass, final biopsy of breast mass by Mammotome System and whole body PET-CT were performed. The immunochemistry stain of specimen of breast mass was used. Results The peripheral blood smear of this patient showed immature erythrocytes, leucocytes and classification of unknown cells which were consistent with BM morphology. The results of BM aspirate and biopsy depicted a hypercellular specimen with disseminated unknown cells infiltration. Unknown cells were positive for CD56 and negative for any hematopoietic markers by flow cytometry. The whole body PET-CT showed that uptake of 18F-FDG of bilateral breast and whole BM was increased, whereas the mass of breast was not presented by CT. PET-CT suggested a probable malignant hematologic disease. The enough specimen of breast mass got from Mammotome System showed embryonal rhabdomyosarcoma, and the tumor cells were positive for MyoD1, Vimentin and Desmin. Conclusions It is a challenge for early diagnosis of solid sarcoma with unknown origin which diffusely infiltrating into BM. Negative expression of hematopoietic markers by flow cytometry plays a role on differential diagnosis in this setting, whereas PET-CT only provides a valuable reference. Enough specimen and immunohistochemical staining could provide solid evidences of diagnosis.

OBJECTIVETo investigate the expression of IL- 23/IL- 17 axis in peripheral blood of patients with primary immune thrombocytopenia （ITP） and its clinical significance.

METHODSThe real-time quantitative reverse transcription-polymerase chain reaction（RT-PCR）was used to determine the expression of IL-23p19, p40, p35, IL-23R, IL-12Rβ1, IL-12Rβ2, IL-17A, IL-17F mRNA in the peripheral blood of 45 ITP patients and 30 healthy controls. The correlations between the expression of IL-23 and IL- 17, platelet counts, serum cytokine concentrations of ITP patients were analyzed. Furthermore, nine newly diagnosed ITP patients were followed up during treatment.

RESULTSThe gene expressions of IL-23p19, p40, IL-23R, IL-12Rβ1, IL-17A, IL-17F in ITP patients were significantly higher than those in healthy controls, the relative expression levels of ITP were 5.58, 2.13, 4.20, 2.45, 4.29, 2.50 times as much as that of healthy controls. And elevated serum IL-23［（198.70±94.56）ng/L vs（50.72±22.97）ng/L, t= 10.06, P<0.001］, IL-17［（85.25±21.97）ng/L vs（11.39±4.27）ng/L, t=21.94，P<0.001］levels were also observed in these ITP patients. In addition, the serum IL-23 level in ITP patients was positively correlated with IL-17（r=0.496, P<0.01）, but negatively correlated with the platelet counts（r=-0.408, P<0.01）, and IL-17 level was negatively correlated with platelet counts（r=-0.464, P<0.01）.

CONCLUSIONThe IL-23/IL- 17 expression in ITP patients was significantly elevated, indicating IL-23/IL-17 play an important role in the pathogenesis of ITP.

Case-Control Studies ; Cytokines ; blood ; Gene Expression ; Humans ; Interleukin-17 ; metabolism ; Interleukin-23 ; metabolism ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; metabolism ; RNA, Messenger

OBJECTIVETo study the efficacy and safety of rituximab (RTX) in the treatment of idiopathic thrombotic thrombocytopenic purpura (ITTP).

METHODSAmong 17 ITTP patients, nine cases of the RTX group were administrated with RTX plus plasma exchange (PEX) and steroids. Eight cases of the control group received PEX plus steroids±other immune inhibitors. Patients received RTX 375 mg/m², 1 per week for 4 weeks. The laboratory parameters, including hemogram, LDH, ADAMTS13 activities and its inhibitors, and the ratio of B lymphocytes in peripheral blood were monitored. The number of PEX, total plasma volumes, remission time, relapse ratio and adverse effects in both groups were compared.

RESULTSThe median number of PEX/median total plasma volumes in the RTX and control group were 5(2-8)/9.6(4.0-15.4) L and 6(4-9)/11.2(7.5-14.6) L, respectively. Patients in the RTX and control group achieved hematologic remission at the median time of 15(5-20) days and 22(7-36) days, respectively. And the median time of immunological remission in the two groups was 2(2-8) and 2(2-4) weeks, respectively. ADAMTS13 activities increased significantly after 2 weeks in both two groups. There was no relapse in the RTX group, while 4 patients relapsed in the control group. The percentage of B lymphocytes in peripheral blood obviously deduced one week after first dose of RTX infusion compared with the level before treatment [(2.19±5.11)% vs (18.39±7.15)%, P<0.001], and began to gradually increase 9 months later. Severe adverse events were not observed in RTX group during the therapeutic procedure and follow-up, but one patient, who had sustained immunologic remission, died of severe pneumonia 7 months later.

CONCLUSIONIn the treatment of ITTP, RTX in conjunction with PEX and steroids appeared to be a safe and effective therapy, with fast and sustained remission in hematology and even in immunology, with lower relapse rate and less adverse effects. But patients needed to be paid attention to prevent and treat infectious events in time.

ADAM Proteins ; ADAMTS13 Protein ; B-Lymphocytes ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic ; Recurrence ; Rituximab ; Steroids

Objective To evaluate the effect of dexmedetomidine on myocardial injury induced by renal ischemia-reperfusion (I/R) injury in rats.Methods Twenty-four male Wistar rats,weighing 280-300 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),group I/R and dexmedetomidine group (group Dex).Renal ischemia was induced by occlusion of bilateral renal arteries for 45 min followed by reperfusion in I/R and Dex groups.At 20 min before ischemia,dexmedetomidine 50 μg/kg was injected intraperitoneally in group Dex,and the rest procedures were similar to those previously described in group I/R.The rats were sacrificed at 24 h of reperfusion and myocardial specimens were obtained for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity.The apoptosis in cardiomyocytes was examined by flow cytometry.Apoptosis index was calculated.The expression of Bcl-2 and Bax was detected by immunohistochemistry,and Bcl-2/Bax ratio was calculated.Results Compared with group S,apoptosis index and MDA content were significantly increased in I/R and Dex groups,Bcl-2/Bax ratio was decreased in group I/R,and Bcl-2/Bax ratio was increased in group Dex.Compared with group I/R,apoptosis index and MDA content were significantly decreased,and SOD activity and Bcl-2/Bax ratio were increased in group Dex.Conclusion Dexmedetomidine can attenuate myocardial injury induced by renal I/R in rats,and the mechanism may be related to inhibited apoptosis in cardiomyocytes and reduced lipid peroxidation.

Objective To explore the diagnostic value of protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in non-infant with acquired deficiency of vitamin K-dependent coagulation factors (ADVKCF).Methods PIVKA-Ⅱ levels were measured by ELISA in 50 patients with ADVKCF on day 0,3,7 after vitamin K treatment.Prothrombin time(PT),APTT,FⅡ ∶ C,FⅦ∶ C,FⅨ∶ C,and FⅩ∶ C were analyzed simultaneously.Twenty healthy subjects were enrolled as controls.Results The average level of PIVKA-Ⅱ in ADVKCF group was (3.83 ± 1.40) μg/L,while (1.30 ± 0.54) μg/L in the control group (P ＜ 0.05).The PIVKA-Ⅱ levels on day 0 and 3 did not show significant difference [(3.83 ± 1.40) μg/Lvs (3.79 ± 0.66) μg/L,P ＞ 0.05],but decreasing significantly on day 7 compared to the control group (P ＜ 0.05).The PIVKA-Ⅱ level was (3.78 ± 1.30) μg/L in patients receiving plasma transfusion,while (3.91 ± 1.49)μg/L in no-plasma-transfusion group (P ＞ 0.05).Coagulation factors Ⅱ,Ⅶ,Ⅸ and Ⅹ activity which decreased significantly before treatment returned to normal range after one week use of vitamin K,leading to complete correction of prolonged APTT and PT (＞ 100 seconds).Conclusions The PIVKAⅡ level in ADVKCF patients is significantly higher than that of healthy subjects within one week treatment of vitamin K,which is not influenced by plasma transfusion.This study suggests that PIVKA-Ⅱ is a more sensitive parameter than APTT,PT and the activity of coagulation factor,which could be a valuable factor in the early diagnosis of ADVKCF.

Objective To explore the clinical features and causes of misdiagnosis of the patients with acquired deficiency of vitamin K-dependent coagulation factors (ADVKDCF). Methods Retrospective analysis was performed with the data from 62 patients with ADVKDCF for etiological factors, clinical manifestations,laboratory examinations, diagnosis and treatments. Results Among the 62 patients, 51 patients were with unknown causes( subgroup A) and 11 were with clear histories of anticoagulant rodenticide poisoning( subgroup B). The presentations of hemorrhage of the patients varied with hematuria as the most common first symptom,followed by skin, mucosa, muscle, internal organs bleeding (28/62). The most common hemorrhage symptom is hematuria. 35 of the 62 patients had hemoglobin(Hb) levels less than 100 g/L due to blood loss( the lowest level was 32 g/L). Thirty-eight patients were misdiagnosed at the first visit and the median time from hemorrhage manifestation to definite diagnosis was 8 days (range,2 to 192 days). ADVKDCF was mostly misdiagnosed as the urinary system diseases (23/38), followed by hemophilia (8/38). Laboratory examinations showed normal platelet count , throm bin time (TT) and normal fibrinogen(Fg) concentration, but prolonged plasma prothrombin time (PT), activated partial prothrombin time (APTT) and international normalized ration (INR). All of patients received high dose vitamin K ( intravenous vitamin K1 with a initial dose of 20 to 240 mg/d and then oral vitamin K4 maintenance) . The bleeding symptoms disappeared 1 day after treatment and the Hb levels increased dramatically. There were significant differences in PT, APTT and INR of the patients before and after treatment( P ＜0. 01 ). Followed by a median follow - up of 8 months , no patient had severe adverse effects or recurrence. Conclusion The hemorrhage presentations of the patients with ADVKDCF are various. The most common hemorrhage symptom is hematuria. The misdiagnosis rate of ADVKDCF is high with urinary systems disorders as the most common misdiagnosis. Sequential treatment with vitamin K is an effective and safe method to prevent recurrence. Early detection of coagulation function is helpful to reduce misdiagnosis possibility.