Objective To assess the value of central venous-to-arterial carbon dioxide difference [ P( cv-a) CO2 ] in evaluation of disease severity and prognosis in patients with septic shock.Methods There were 45 consecutive resuscitated septic shock patients from April 2009 to October 2010 included immediately after their admission into our ICU.The patients were divided into low P(cv-a) CO2 group and high P(cv-a) CO2 group according to a threshold of 6 mm Hg ( 1 mm Hg=0.133 kPa).All patients were treated by early goal directed therapy (EGDT).The parameters of hemodynamics,lactate clearance rate,the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ ) score,the sequential organ failure assessment (SOFA)score,6 h rate of EGDT achievement,the ICU mortality and 28 days in-hospital mortality were recorded for all patients.Results There were 30 patients in the low P(cv-a) CO2 group,and 15 in the high P(cv-a)CO2group.There were no significant differences between low P(cv-a) CO2 and high P(cv-a) CO2 patients in age,APACHE Ⅱ score and SOFA score (all P ＞ 0.05 ).Compared with the high P(cv-a)CO2 group,the low P(cv-a) CO2 group had higher cardiac index ( CI ) and 24 h CI,higher delivery O2 ( DO2 ) and 24 h DO2,higher central venous oxygen saturation ( ScvO2 ) [ (74 ± 9) ％ vs (67 ± 8) ％ ],lower lactate [ ( 3.4 ± 2.1 )mmol/L vs (5.7 ± 4.5 ) mmol/L] and higher △SOFA score [ (0.7 ± 1.8 ) vs ( - 0.4 ± 1.1 ) ],lower 24 h SOFA score [ (7.8 ± 2.0) vs (9.8 ± 2.0 ) ],higher 6 h rate of EGDT achievement ( 83.3％ vs 53.3 ％ )(P ＜ 0.05 ),however,there were no differences in 28 days mortality and ICU mortality between the two groups ( P ＞ 0.05 ).Conclusion P(cv-a) CO2 might be an indicator for predicting the severity of patients with septic shock and evaluating tissue perfusion.

Objective To express a recombinant protein TFPR1 ( the functional region of the snake venom proteins from Trimeresurus flavoviridis) in Pichia pastoris expression system. Methods The target gene was codon-optimized and synthesized according to the sequence of the conserved structural do-main of triflin and then cloned into the Pichia pastoris expression vector pPICZαA to construct the recombi-nant expression plasmid pPICZαA-TFPR1. The recombinant plasmid pPICZαA-TFPR1 was electroporated into the yeast strain X33. The transformed strains carrying expression plasmid were screened out with Zeocin and then induced by methanol to express the recombinant protein TFPR1. ELISA was performed for the screening of positive clones. SDS-PAGE and Western blot were used for further identification of the ex-pressed products. Results The recombinant plasmid pPICZαA-TFPR1 was successfully constructed. The recombinant protein TFPR1 was expressed in a secreted form at a molecular weight of 16×103. Conclusion The recombinant protein TFPR1 was successfully expressed in Pichia pastoris expression system, which laid a foundation for further researches on its biological function and application as an adjuvant.

OBJECTIVE: To determine the biological activity of ellagic acid extracted from gallnut against nasopharyngeal carcinoma and its molecular mechanism. METHODS: Nasopharyngeal carcinoma 5-8F cells were treated with 2, 4, 6 μg/mL ellagic acid for 48 h in vitro. The cell proliferation and cell apoptosis were analyzed by MTT and Hoechst33258 stain. The cell cycle and protein expression were measured by flow cytometry and Western blot. RESULTS: Ellagic acid inhibited the proliferation of 5-8F cells. The inhibition rates were (29.35±4.95)%, (53.32 ±4.44)% and ( 61.75 + 6.93)%, respectively, with significant difference from the control group (P<0.01). S phase cells in the experimental groups were (25.47±0.74)%, (28.08±1.41)% and (35.49±0.66)%, respectively, with significant difference (P<0.01) from the control group (21.26±0.70)%. Cells in the experimental groups showed nuclear pyknosis, karyorrhexis and poptotic cell morphology. The expression of COX-2 and stathmin in 5-8F cells was down-regulated with increased drug concentration. CONCLUSION Ellagic acid extracted from gallnut has activity against nasopharyngeal carcinoma cells, and its mechanism may be related to down-regulated expression of COX-2 and stathmin.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; genetics ; metabolism ; Down-Regulation ; drug effects ; Ellagic Acid ; pharmacology ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Plant Extracts ; pharmacology ; Stathmin ; genetics ; metabolism

Objective To explore the effects of transcutaneous electrical acupoint stimulation(TEAS)combined with multi-model analgesia on infrared thermal imaging characteristics and pain after total knee arthroplasty(TKA).Methods A total of 74 patients with TKA were divided into the treatment group and the control group according to random number table method,with 37 cases in each group.The control group was treated with multi-model analgesia,and the treatment group was treated with TEAS on the basis of multi-model analgesia for 30 min,once in the morning and afternoon before the patient's rehabilitation exercise 1-7 days after surgery.The infrared thermal imaging data,visual analogue scale(VAS)score,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score and pain threshold of the two groups were recorded and analyzed before and at different time points after operation.Results There were 2 cases dropped out in each group.Compared with before surgery,both groups had an increase in knee joint temperature on the surgical side 14 days after surgery(P<0.05),and the temperature in the treatment group was lower than that in the control group(P<0.05).The self knee temperature difference in the treatment group was lower than that in the control group 14 days after surgery(P<0.05).Compared with before surgery,the VAS score of the treatment group decreased 3 and 7 days after surgery(P<0.05),while the VAS score of the control group decreased 7 days after surgery(P<0.05);compared with the control group at 3 and 7 days after surgey,the VAS score of the treatment group was lower than that of the control group.Compared with before surgery,the WOMAC scores of both groups increased 7 days after surgery(P<0.05);after 7 days of surgery,the WOMAC score of the treatment group was lower than that of the control group(P<0.05).Compared with before surgery,the pain threshold values of both groups increased 7 days after surgery(P<0.05);compared with the control group at 3 and 7 days after surgery,the pain threshold values of the treatment group was higher than that of the control group(P<0.05).Conclusion TEAS combined with multi-model analgesia can reduce the temperature of the knee joint,relieve the pain of the operated limb,and promote the early functional recovery of the knee joint after TKA.Infrared thermal imaging technology has a certain application value in indirectly assessing the degree of postoperative pain and detecting early infection of the affected limb.

Objective To explore the treatment effects and mechanism of Fangji Huangqi Xiaozhong Prescription in metabolic syndrome phenotype osteoarthritis(MS-OA)based on PPARγ/NF-κB signaling pathway.Methods SD rats were randomly divided into sham-operation group,OA group,MS-OA group,Western medicine group,and TCM high-and low-dasage groups.The modified Hulth method was used to make the OA model,and OA model was added with high-carbohydrate high-fat diet to make the MS-OA model.TCM high-and low-dosage groups were given 15.12,7.56 g/kg Fangji Huangqi Xiaozhong Prescription for gavage.The Western medicine group was given 16.2 mg/kg of losoprofen sodium by gavage,while the other groups were given physiological saline by gavage once a day for 6 consecutive weeks.Rat body mass was measured,biochemical detection of blood lipids and blood glucose was conducted,ELISA was used to detect the contents of serum TNF-α,IL-1β,IL-10 and leptin,morphological changes in cartilage tissue were observed using safranin O-fixed green and HE staining,immunohistochemical staining was used to detect expressions of Acan,ColⅩ,MMP13,TNF-α,IL-1β and PPARγ in cartilage tissue,Western blot was used to detected the expression of PPARγ,NF-κBp65 and p-NF-κBp65 protein in cartilage tissue.Results Compared with the sham-operation group,body mass and serum TC,TG,LDL-C,TNF-α,IL-1β and leptin of MS-OA group increased significantly(P<0.01),the contents of HDL-C and IL-10 decreased(P<0.01),cartilage tissue degeneration was significant,and the Mankin score increased(P<0.01),the expression of ColⅩ,MMP13,TNF-α,IL-1β,p-NF-κBp65 protein increased(P<0.05,P<0.01),and the expression of Acan and PPARγ protein decreased(P<0.01).Compared with the MS-OA group,the contents of serum TC,TG,LDL-C,TNF-α and leptin decreased in TCM high-dosage group(P<0.05,P<0.01),the content of IL-10 increased(P<0.05),the pathological damage of cartilage tissue improved,the Mankin score decreased(P<0.01),the expressions of ColⅩ,MMP13,TNF-α,IL-1β and p-NF-κBp65 protein in cartilage tissue decreased(P<0.05,P<0.01),and the protein expressions of Acan and PPARγ protein increased(P<0.01,P<0.05).Conclusion Fangji Huangqi Xiaozhong Prescription can improve lipid metabolism disorder,improve intra-articular inflammatory environment,balance cartilage metabolism,and delay cartilage degeneration in MS-OA rats.Its mechanism may be related to the regulation of PPARγ/NF-κB signaling pathway.

Objective:To evaluate consistency between 2-fold serial and 4-fold serial diluted neutralization tests against Enterovirus A71 (EV-A71) in estimating titer, Geometric mean titer (GMT), seroprevalence, and seroincidence.Methods:Based on a prospective cohort of 1-9 years old children, mothers and infants established in Anhua County, Hunan Province, during 2013-2018, from which 92 participants with a total of 386 blood specimens were sampled and tested with a 2-fold serial dilution and a 4-fold serial dilution neutralization tests against EV-A71 at the same time. Agreement was estimated using the Bland-Altman method. Stratified analysis was conducted to estimate effect dilution approach on GMT, seroprevalence and seroincidence.Results:The mean difference (0.04, 95% CI:-0.02-0.10) between the two dilution approaches was not significant. However, the limits of agreement (LOA) (-1.12-1.21), with the 95% confidence interval of upper LOA (1.10-1.31) and of lower LOA (-1.22--1.02), significantly exceeded the Clinic accept interval (-1, 1) indicating insufficient agreement between the two approaches in practice. While the dilution approaches did not affect estimates of GMT of the total population and the positive population, and seroincidence with seroconversion only, the differences were 2, 6 and 2%, respectively ( P>0.05). Estimates of seroincidence with at least 4-fold increase and seroconversion/4-fold increase were significantly higher using a 4-fold dilution neutralization test compared to the 2-fold dilution neutralization test with 8% (95% CI: 1%-12%) and 9% (95% CI: 1%-17%), respectively. Conclusion:The 2-dilution and 4-dilution neutralization tests yielded comparable results when estimating the population′s GMT; however, the difference between the two is not negligible when assessing the seroincidence.

Objective:To evaluate consistency between 2-fold serial and 4-fold serial diluted neutralization tests against Enterovirus A71 (EV-A71) in estimating titer, Geometric mean titer (GMT), seroprevalence, and seroincidence.Methods:Based on a prospective cohort of 1-9 years old children, mothers and infants established in Anhua County, Hunan Province, during 2013-2018, from which 92 participants with a total of 386 blood specimens were sampled and tested with a 2-fold serial dilution and a 4-fold serial dilution neutralization tests against EV-A71 at the same time. Agreement was estimated using the Bland-Altman method. Stratified analysis was conducted to estimate effect dilution approach on GMT, seroprevalence and seroincidence.Results:The mean difference (0.04, 95% CI:-0.02-0.10) between the two dilution approaches was not significant. However, the limits of agreement (LOA) (-1.12-1.21), with the 95% confidence interval of upper LOA (1.10-1.31) and of lower LOA (-1.22--1.02), significantly exceeded the Clinic accept interval (-1, 1) indicating insufficient agreement between the two approaches in practice. While the dilution approaches did not affect estimates of GMT of the total population and the positive population, and seroincidence with seroconversion only, the differences were 2, 6 and 2%, respectively ( P>0.05). Estimates of seroincidence with at least 4-fold increase and seroconversion/4-fold increase were significantly higher using a 4-fold dilution neutralization test compared to the 2-fold dilution neutralization test with 8% (95% CI: 1%-12%) and 9% (95% CI: 1%-17%), respectively. Conclusion:The 2-dilution and 4-dilution neutralization tests yielded comparable results when estimating the population′s GMT; however, the difference between the two is not negligible when assessing the seroincidence.

Objective To study the clinical characteristics of outpatients with hand,foot and mouth disease (HFMD) caused by different serotypes of enteroviruses.Methods This was a prospective study.From February 2017 to March 2018,563 outpatients with HFMD were enrolled by systematic sampling in the Department of Infectious Diseases,Henan Children's Hospital.Throat swabs were collected to determine the serotypes via PCR.Demographic,clinical,and laboratory data were collected by standard questionnaire.All cases were followed up twice at 2 and 9 weeks after the initial outpatient visit through telephone interview.A total of 563 cases were enrolled and 555 (98.6％) cases were positive for human enteroviruses,including 338 (60.9％) males.Analyses were stratified by enterovirus serotypes,Chi square test or Fisher's exact test,Rank sum test was used for comparison among different groups.Results The age of 555 cases was 24.2 (16.4,41.3) months.Among them 44.0％ (224 cases) were identified as coxsackievirus (CV)-A6,while 189 cases,35 cases,14 cases and 73 cases were identified as CV-A16,enterovirus (EV)-A71,CV-A10 and other serotypes,respectively.Fever (≥37.5 ℃C) was present in 51.4％(285/555) of laboratory confirmed cases.The proportions of fever in cases of CV-A6 (68.9％(168/244)) and CV-A10 (12/14) were significantly higher than those in cases of CV-A16 (31.7％(60/189),x2=57.344,14.313,both P=0.000),other serotypes (43.8％(32/73),x2=15.101 and 8.242,P=0.000 and 0.004) and EV-A71 (37.1％(13/35),x2=13.506 and 9.441,P=0.000 and 0.002) respectively.There was no significant difference between CV-A6 and CV-A10 in presentation of fever (x2=1.785,P=0.182).There were 359 cases (64.7％) with eruptions in mouth,hands,feet and buttocks.Cases infected with EV-A71 had the highest proportions (74.3％(26/35)) of rash emerging simultaneously in mouth,hands,feet,and buttocks.The proportion in cases of CV-A 16,CV-A6,CVA 10 and other serotype were 73.5％ (139/189),61.9％ (151/244),7/14 and 49.3％ (36/73),respectively.The proportion of rash on other parts of body,such as face,limbs or torso in cases infected with CV-A6 (16.8％ (41/244)) was the higherest and the proportion in cases of CV-A16,EV-A71,CV-A10 or other serotypes were 8.5％(16/189),5.7％(2/35),1/14,6.8％(5/73),respectively.None of these cases developed serious complications.Desquamation occurred in 45.5％ (179/393) cases 7.5 (5.0,9.0) days after disease onset and 13.5％ (53/393) cases showed onychomadesis 31.0 (18.0,33.5) days after disease onset.The proportion of desquamation and onychomadesis associated with CV-A6 (64.2％ (95/148) and 31.8％ (47/148)) was significantly higher than CV-A16 (31.8％ (49/154) and 1.3％ (2/154),x2=33.601 and 52.482,both P=0.000) and other serotypes (38.0％(19/50) and 6.0％(3/50),x2=10.236 and 12.988,P=0.001 and 0.000).Desquamation appeared more in cases of CV-A6 than in cases of CV-A10 (2/11,x2=9.386,P=0.002),with the proportion of onychomadesis higher in CV-A6 than in EV-A71 (3.3％ (1/30),x2=11.088,P=0.001).Conclusion Clinical manifestation such as fever,rash emerging parts,desquamation and onychomadesis are different among outpatient HFMD cases infected with CV-A16,CV-A6,EV-A71,CV-A10 and other enteroviruses.

A retrospective analysis of the clinical data of seven acute B-lymphoblastic leukemia (B-ALL) patients with TCF3-HLF fusion gene-positive admitted to the First Affiliated Hospital of Soochow University from June 2017 to August 2022 was conducted to summarize their clinical features and prognoses. The seven B-ALL patients comprised four males and three females, with a median age of 18 (11-33) years. Five patients tested positive for CD33 expression, and four patients had a normal karyotype. Two patients had hypercalcemia at the initial diagnosis, and one patient developed hypercalcemia at relapse. Six patients presented with coagulation dysfunction at diagnosis. After induction chemotherapy, five out of seven patients achieved complete remission, of which four subsequently relapsed. Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy. Three patients underwent chimeric antigen receptor T cell therapy, whereas three patients subsequently underwent hematopoietic stem cell transplantation. Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

OBJECTIVETo study clinical characteristics of refractory or relapsed DNMT3A⁺ cytogenetically normal acute myeloid leukemia（CN-AML）patients, and to explore the overall response rate（ORR）and side effects of these patients followed the therapy including decitabine with CAG or CAGlike regimen.

METHODSIn this study we retrospectively analyzed 53 refractory or relapsed CN- AML patients receiving the therapy including decitabine combined with CAG and CAG- like regimen in our center from April 2011 to October 2014. The clinical characteristics and ORR were further analyzed. Based on gene mutations, these patients could be divided into 2 groups: DNMT3A⁺ AML patients（n=24）and DNMT3A- AML patients（n=29）.

RESULTSThe median age of DNMT3A⁺AML patients was 46 years old, higher white blood cells and bone marrow blasts were observed in DNMT3A+ AML group. The ORR and complete response（CR）rate of DNMT3A+ group were 62.50% and 54.17%, respectively. No differences were observed in ORR and CR rates（P>0.05）between these two groups. DNMT3A⁺/FLT3-ITD⁺ CN-AML patients（n=14）had higher ORR and CR rates than DNMT3A-/FLT3-ITD⁺CN- AML patients（n=15）（P= 0.040 and 0.042, respectively）. The one- year overall survival （OS） of DNMT3A⁺ AML group and DNMT3A- AML group were 59.58% , 54.09% , no differences were observed （P=0.438）. 25 patients received further therapy of allo-HSCT, the one-year OS of DNMT3A⁺ CN-AML was 87.50% and one-year disease free survival（DFS）was 72.73%, while the one- year OS was 61.54% and one- year DFS was 58.02% in DNMT3A⁻ group. No differences were observed between 2 groups （P=0.456, 0.217）.

CONCLUSIONDecitabine combined with CAG or CAG-like regimen was an effective and safe treatment for refractory or relapsed CN- AML patients. Compared to DNMT3A⁻/FLT3- ITD⁺ CN- AML patients, DNMT3A⁺/ FLT3-ITD⁺ CN-AML patients had higher ORR and CR rates. Decitabine bridged hematopoietic stem cells transplant could likely improve the survival of refractory or relapsed CN-AML patients.

Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; analogs & derivatives ; therapeutic use ; Cytarabine ; therapeutic use ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Mutation ; Remission Induction ; Retrospective Studies