Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To investigate the clinical effect of monosialotetrahexosyl ganglioside in the treatment of neonatal intracranial hemorrhage.Methods From January 2016 to December 2018,142 neonates with intracranial hemorrhage admitted to the Maternal and Child Health Hospital of Zhoushan were randomly divided into observation group (71 cases) and control group (71 cases) according to the digital table.The control group was treated with routine treatment,while the observation group was treated with ganglioside needle on the basis of the control group.Both two groups were treated for 14 days.The therapeutic effects,muscle tone recovery time,reflex recovery time and consciousness recovery time were compared.The changes of neurobehavioral assessment score (NABA score),TNF-αt,IL-1β,MMP-2,T IMP-1 and NSE levels before and after treatment were compared.Results The total effective rate of the observation group (92.96％) was higher than that of the control group (77.47％) (x2 =6.762,P ＜ 0.05).The recovery time of muscle tension,reflex and consciousness in the observation group [(7.68 ± 1.29) d,(6.83 ± 1.20) d and (8.34 ± 1.54) d] were shorter than those in the control group [(10.25 ± 2.31) d,(9.17 ±1.86) d and (10.53 ± 1.08) d] (t =8.185,8.908,9.811,all P ＜ 0.05).After treatment,the NABA score of the observation group [(40.37 ± 0.65) points] was higher than that of the control group [(37.16 ± 0.93) points] (t =23.838,P ＜ 0.05).The serum levels of TNF-α [(26.37 ± 4.25) pg/L],IL-1β [(16.74 ± 3.24) ng/L],MMP-2 [(78.39 ± 16.57)g/L],TIMP-1 [(179.32 ± 17.65) ng/mL] and NSE [(13.52 ± 2.19) g/L] in the observation group were lower than those in the control group [(53.21 ± 7.39) pg/L,(28.93 ± 5.64) ng/L,(97.42 ±12.63) g/L,(238.63 ± 28) ng/mL and (21.43 ± 2.89) μg/L] (t =26.529,15.792,7.696,14.938,1 8.381,all P ＜ 0.05).Conclusion Ganglioside has good therapeutic effect on neonatal intracranial hemorrhage.It can reduce the serum levels of TNF-α,IL-1β,MMP-2,TIMP-1 and NSE,and improve the neurobehavioral function of neonates.

Objective To investigate the clinical effects and safety of terbutaline combined with budesonide atomized inhalation in the treatment of children with bronchiolitis obliterans .Methods 140 cases of children with bronchiolitis obliterans from June 2015 to June 2017 were selected as research subjects , and they were randomly divided into control group and observation group according to the digital table ,with 70 cases in each group .The control group was given budesonide atomized inhalation alone ,and the observation group was given terbutaline combined with budesonide atomized inhalation .The clinical effects ,disappeared time of symptoms ,levels of IL-4 and INF-γbefore and after treatment and incidence rate of adverse effects in the two groups were compared .Results The excellent effective rate and total effective rate of the control group were 28.57％,78.57％,respectively,which were significantly lower than those of the observation group (44.29％,95.71％) (χ2 =9.73,8.60,all P<0.05).The disappeared time of symptoms of the observation group was significantly shorter than those of the control group ( t=2.67,3.15,2.20, 2.36,all P<0.05).The levels of IL-4 and INF-γafter treatment of the observation group were significantly higher than those of the control group and before treatment (t=2.44,2.71,3.07,3.66,2.94,3.26,all P<0.05).The incidence rates of adverse effects of the control group and the observation group were 8.57％,11.43％,respectively, there was no statistically significant difference between the two groups (χ2 =1.49,P>0.05).Conclusion Terbutaline combined with budesonide atomized inhalation in the treatment of children with bronchiolitis obliterans can efficiently control the disease progression ,shorten the clinical disease course ,regulate the levels of IL -4 and IFN-γand not aggravate the adverse drug reactions .

OBJECTIVE:To observe the clinical efficacy and safety of Ligustrazine injection,α-ketoacid combined with levam-lodipine in the treatment of chronic renal failure. METHODS:92 patients with chronic renal failure were randomly divided into ob-servation group(46 cases)and control group(46 cases). All patients received electrolyte,vitamins and essential amino acid,low salt,low fat,hypoglycemic and hypolipemic,anti-infection,correcting anemia and other conventional symptomatic treatment. Based on it,control group received 8 Compound α-ketoacid tablets,3 times a day + 1 Benzenesulfonic acid levamlodipine tablet, once a day. Observation group additionally received 150 mg Ligustrazine hydrochloride injection,adding into 250 ml 5% Glucose injection,intravenous infusion,once a day. The treatment course for both groups was 3 months. Clinical efficacy,and urea nitro-gen (BUN),serum creatinine (Scr),serum cystatin (CysC),low-density lipoprotein cholesterol (LDL-C),total cholesterol (TC),triglyceride (TG) levels before and after treatment and the incidence of adverse reactions in 2 groups were observed. RE-SULTS:The total effective rate in observation group was significantly higher than control group,the difference was statistically sig-nificant(P<0.05). Before treatment,there were no significant differences in the BUN,Scr,CysC,LDL-C,TC and TG between 2 groups(P>0.05). After treatment,BUN,Scr,LDL-C,TC and TG in 2 groups were significantly lower than before,and obser-vation group was lower than control group,CysC was significantly higher than before,and observation group was higher than con-trol group,the differences were statistically significant (P<0.05). And there was no significant difference in the incidence of ad-verse reactions(P>0.05). CONCLUSIONS:Based on conventional treatment,Ligustrazine injection,α-ketoacid combined with le-vamlodipine show obvious efficacy in the treatment of chronic renal failure,they can improve the renal functions,with good safety.

OBJECTIVETo observe treatment response, survival, safety and the improvement of ECOG in patients with refractory multiple myeloma (MM) with serious heart failure after the administration of continuous low-dose of cyclophosphamide combined with prednisone (CP).

METHODSFrom January 2005 to September 2013, a total of 75 patients were treated by metronomic chemotherapy with continuous low-dose cyclophosphamide (50 mg/d) and prednisone (15 mg/d).

RESULTSAmong the 75 patients, 2 were lost for follow-up. In the 73 available patients, the overall response was 64.4%, including 2 patients (2.7%) with complete remission (CR), 4 cases (5.5%) very good partial remission (VGPR), and 24 patients (32.9%) partial remission (PR). The median survival was 12 months (1-70 months) with a median onset time of 90 days (16-120) and a median progressive freedom survival of 12 months (1-60). The level of B-type natriuretic peptide in responders declined significantly, as compared to no responders [(336.6 ± 30.3) ng/L vs (906.4 ± 104.8) ng/L, P<0.01]. Common adverse events were as follows: 32 (43.8%) cases of bone marrow suppression, 26 (35.6%) cases of infection, 8 cases of dizzy as well as sleepiness (11.0%), 7(9.6%) cases of Cushing syndrome, 4 (5.5%) cases of secondary diabetes mellitus, and 3 (4.1%) cases of edema respectively.

CONCLUSIONThe metronomic chemotherapy of cyclophosphamide combined with prednisone had satisfactory impact on the treatment outcome, including the improvement of cardiac functions and physical capacities, better survival and safety in refractory MM with serious heart failure. It provides a novel regimen for such patients.

Antineoplastic Combined Chemotherapy Protocols ; Clinical Protocols ; Cyclophosphamide ; Heart Failure ; Humans ; Multiple Myeloma ; Prednisone ; Remission Induction ; Treatment Outcome

OBJECTIVE:To study the effect of Yi medicine Acanthopanax trifo-liatus alcohol extract on the contents of IL-1β, IL-6,IL-10,NO,TNF-αand PGE2 in serum of adjuvant-induced arthritis(AA)rats. METHODS:60 SD rats were randomly divid-ed into normal control group (distilled water),model group (distilled water),positive control group (nimesulide,0.03 g/kg), A. trifo-liatus high-dose,medium-dose and low-dose groups [7,3.5,1.75 g(medicinal material)/kg]. Except for normal control group,other groups were given 0.1 ml Freund’s complete adjuvant on posterior right toe to induce AA model. After modeling, those groups were given relevant medicine intragastrically,once a day. The contents of IL-1β,IL-6,IL-10,TNF-α,NO,PGE2 in rat serum were measured 30 days later. The pathological morphology of the rat ankle was also observed. RESULTS:Compared with normal control group,the contents of IL-1β,IL-6,TNF-α,NO and PGE2 in serum increased in model group while the content of IL-10 decreased,with statistical significance (P<0.01);compared with model group,the contents of IL-1β,IL-6,TNF-α,NO and PGE2 in serum decreased in A. trifo-liatus high-dose groups while the content of IL-10 decreased,with statistical significance (P<0.05). The pathology results showed that part of the slice synoviocytes mild thickening,fibrous tissue mild hyperplasia,in-flammatory cells infiltration at varying degrees,macrophages mild hyperplasia in A. trifo-liatus groups. Those changes were not found in normal control group. CONCLUSIONS:A. trifo-liatus alcohol extract has an obvious anti-inflammatory action to AA mod-el rat,by a mechanism of decreasing the contents of IL-1β,IL-6,TNF-α,NO and PGE2,and increasing the content of IL-10.

Objective To investigate the expression types of protease-activated receptors (PAR) in human gingival fibroblasts(HGF) and the functions of PAR in periodontitis.Methods Primary HGF were cultured.Reverse transcription PCR(RT-PCR) was used to detect the expression of PAR in HGF.Recombinant gingipain R (rRgp) was applied to HGF.The change of PAR expression on the cell surface was analyzed by real-time quantitative RT-PCR,and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of the interleukin(IL)-6 production from HGF.The results of RT-PCR and ELISA were statistically analyzed using the two independent samples t-test of SPSS10.0 software.Results HGF expressed PAR-1 and PAR-3.The expression of PAR-1 and PAR-3 changed after two rRgp treatment with HGF cells.The relative expression of PAR-1 was decreased from 1.04 ± 0.31 to 0.67 ± 0.11 and 0.31 ±0.11.The relative expression of PAR-3 was decreased from 1.01 ±0.44 to 0.79 ±0.13 and 0.44 ± 0.12 (P ＜ 0.05).The level of IL-6 was increased after rRgp treatment for 8 h.The control group was (18.77 ±4.09) μg/L,the rRgp treatment groups were (179.36 ± 15.81) and (320.56 ± 26.19) μg/L respectively.Conclusions HGF expressed PAR-1 and PAR-3 and were involved in periodontal inflammation.

Objective To evaluate the efficacy andtolerability of continuous low-dose cyclophosphamide and prednisone treatment of relapsed and refractory multiple myeloma. Methods84 relapsed and refractory multiple myeloma patients were enrolled, including 46 males and 38 females, the assess patients of 81 cases with average age of 69.7 (45-91)years. They were treated continuous with oral cyclophosphamide (50 mg/d) and prednisone (15 mg/d) and monthly follow-up.ResultsAverage follow-up time were 23.5(1-71)months.The assessed patients were 81 cases,with 52 cases (64.2 ％) responded.There were 2 cases(2.5 ％)CR,21 cases(25.9 ％) of PR,29 cases(35.8 ％)MR,19 cases(23.5 ％)NC and 10 cases (12.3 ％)PD.The median time to response was 2 months.In the patients who responded to the treatment,the median progression-free survival(PFS)and overall survival (OS) were 18(95 ％CI 12.8-23.2),29(95 ％CI 24.1-33.9)months.In the non-responding patients,the PFS and OS were 4(95 ％ CI 2.2-5.8) and 6(95 ％ CI 4.9-7.1)months.Two groups were statistically significant(P＜0.05).The most common toxicities included fatigue,nausea, neutropenia, hyperglycemia and lung infection. No patient withdrew from the study because of toxicity. Conclusions Continuous low-dose cyclophosphamide combined prednisone is a treatment options for relapsed and refractory MM patients.

Objective To investigate the characteristic and its clinical value of tumor necrosis factor (TNF)-α and its receptor, interleukin (IL)-1β and its receptor in serum and bronchoalveolar lavage fluid(BALF) in patients with pulmonary tuberculosis and to determine the role of them in the immunopathogenesis of tuberculosis. Methods The concentrations of TNF-α,soluble TNF receptor (sTNF-R) Ⅰ, IL-1β and IL-1 receptor were measured using sandwish ABC-enzyme-linked immunosorbent assay (ELISA) method in serum and BALF of 46 patients with active tuberculosis and 21 patients with inactive tuberculosis, and in the serum of 20 cases of healthy control. Meanwhile the above-mentioned cytokine levels in serum and BALF of 19 patients with active tuberculosis were followed up. Differences between groups were assessed for significance by t test. Results The TNF-α,sTNF-R Ⅰ, IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of active tuberculosis group were (286.2±96.3) pg/L,(2 431.5±1 124.6) pg/L,(58.6±3.2) pg/L,(162.4±17.1) pg/L and 0.06±0.01, respectively, which were all significantly higher than those with inactive tuberculosis group (t=3.36,3.25,2.95,2.27 and 3.12 respectively; P<0.05). The TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of cavernous tuberculosis group were (381.4±106.4) pg/L,(2 824.7±1 318.5) pg/L,(66.4±4.6) pg/L,(176.4±18.7) pg/L and 0.07±0.01, respectively,which were all significantly higher than those of non-cavernous tuberculosis group (t= 3.46,2.37, 3.19, 2.99 and 3.22, respectively; P<0.05). After 2-month' antituberculosis treatments, among 19 cases, the TNF-α,sTNF-R Ⅰ,IL-1β and IL-1 receptor levels and TNF-α/sTNF-R Ⅰ ratios in BALF of 16 cases were significantly lower than those at the beginning of treatments (t= 3.26,3.17, 3.28, 2.92 and 3.12 respectively; P<0.01). Meanwhile, their clinical symptoms improved, sputum smear negative, lesions on chest X-ray resolved and the cavity shrinked or closed. Conclusions TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor are likely to be involved in the immunopathogenesis of tuberculosis. Detection of TNF-α, sTNF-R Ⅰ, IL-1β and IL-1 receptor levels in the serum and BALF is helpful to understand the activity of disease, determine the clinical pattern of disease,assess the prognosis of disease and monitor the therapeutic effect in patients with pulmonary tuberculosis.

OBJECTIVETo study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepa1-6.

METHODSRetrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL.

RESULTS(1)In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared.

CONCLUSIONSThe antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1BBL

4-1BB Ligand ; Animals ; Cell Division ; immunology ; Female ; Liver Neoplasms, Experimental ; immunology ; pathology ; prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Plasmids ; genetics ; immunology ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; genetics ; immunology