Objective:To determine the expression and diagnostic value of peripheral blood lymphocytes and functional activation status in non-Hodgkin lymphoma with hemophagocytic lymphohistiocytosis (NHL-HLH) .Methods:We retrospectively analyzed clinical data from 30 newly diagnosed NHL-HLH patients admitted to Jiangsu Province Hospital from September 2022 to September 2023. We assessed peripheral blood lymphocytes and activation status by flow cytometry. Forty newly diagnosed patients with NHL who received treatment at our hospital during the same period and had lymphocyte and functional activation indexes were selected as the control group. The differences in relative and absolute lymphocyte counts and functional activation indexes between the two groups were compared. The optimal cutoff values for continuous variables were calculated from the receiver operating characteristic curve and logistic regression analysis was used to evaluate the risk factors in NHL patients with HLH.Results:A total of 30 NHL-HLH patients were evaluated, including 12 T-cell lymphoma and 18 B-cell lymphoma patients. Forty individuals were in the control group, which included 19 T-cell lymphoma and 21 B-cell lymphoma patients. The absolute counts of CD3 + T, CD4 + T, CD8 + T, and NK cells, along with the relative count of NK cells, were significantly lower in the HLH group compared with that in the control group (all P values<0.01) . The expression of CD38 and HLA-DR on CD8 + T-cell activated subgroups was significantly higher in the NHL-HLH group compared with that in the control group (CD8 +CD38 +/CD8 + T expression median: 57.4% vs 21.5%, P<0.001; CD8 +CD38 +/CD8 + T expression median: 49.7% vs 33.5%, P=0.028, respectively) . In addition, CD28 expression on CD4 + and CD8 + T cells was significantly higher in NHL-HLH patients ( P<0.01) . ROC curve and multivariate logistic regression analyses revealed that absolute NK cell count ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were risk factors for predicting the occurrence of NHL-HLH patients. The sensitivity and specificity of the regression model were 86.7% and 86.1%, respectively, with an area under the curve of 0.94 ( P<0.001) . Conclusions:In NHL patients with HLH, there was a significant reduction in the absolute number of peripheral blood lymphocyte subpopulations, whereas T-cell function was notably activated. Specifically, absolute counts of NK cells ≤72.0 cells/μl, CD4 +CD28 +/CD4 + T >94.2%, and CD8 +CD28 +/CD8 + T >38.4% were identified as risk factors for predicting the development of NHL-HLH patients. This will assist in early clinical diagnosis and treatment.

AIM:To investigate the effects and mechanism of Xin-Tong-Tai granule on oxidized low-density li-poprotein(ox-LDL),intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in ApoE-/-mice with atherosclerosis(AS).METHODS:A total of 72 SPF-grade healthy male ApoE-/-mice aged 6～8 weeks were fed with high-fat diet for 12 weeks to replicate AS models,and 12 SPF-grade healthy male C57BL/6J wild mice were fed with ordinary diet as the control group.After the corresponding drugs were administered for 8 weeks,the body weight and general condition of mice in each group were observed.The serum levels of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were detected by biochemi-cal kits.The pathological structures of aorta were observed by HE and oil red O staining.The levels of serum ox-LDL and aortic ICAM-1 and VCAM-1 were detected by ELISA.The protein levels of NADPH oxidase 4(NOX4),NOX subunit p22phox,inhibitor of κB kinase-α(IKK-α),IKK-β and nuclear factor-κB(NF-κB)in aorta were detected by Western blot.RESULTS:Compared with control group,the mice in model group showed increased body weight(P<0.05),dull and lo-cal shedding hair,slow grasping response,increased serum TC,TG and LDL-C levels,decreased serum HDL-C level(P<0.05),increased the levels of serum ox-LDL and aortic ICAM-1 and VCAM-1(P<0.05),and increased protein expres-sions of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta(P<0.05).Compared with model group,the body weight of mice in each treatment group decreased(P<0.05),the hair loss and the response flexibility were also improved.The se-rum levels of TC,TG and LDL-C decreased and HDL-C increased(P<0.05).The levels of serum ox-LDL and aortic ICAM-1(except the low-dose Xin-Tong-Tai granule group)and VCAM-1 decreased(P<0.05).The protein levels of NOX4,p22phox,IKK-α,IKK-β and NF-κB in aorta decreased(P<0.05).HE and oil red O staining showed that typical AS plaques could be seen in blood vessels of the model group,and the red-stained areas were widely distributed.The above lesions were alleviated to different degrees in each treatment group compared with model group.CONCLUSION:Xin-Tong-Tai granule reduces the atherosclerotic plaque area of ApoE-/-mice induced by high-fat diet,decreased serum TC,TG and LDL-C levels,increased HDL-C level,decreased the levels of serum ox-LDL and aorta ICAM-1 and VCAM-1,and inhibited protein expression of NOX4,p22phox,IKK-α and IKK-β in the aorta,thereby attenuating AS.

Objective To compare and analyze the results of hysterosalpingography(HSG)in primary infertility patients who received ultra-liquefied ethiodized poppyseed oil-based contrast medium or iodized oil-based contrast medium.Methods A total of 212 patients with primary infertility who received HSG examination were enrolled,of which 96 patients were in the ultra-liquefied ethiodized pop-pyseed oil-based contrast medium group,while 116 patients were in the iodized oil-based contrast medium group.The visual analogue scale(VAS)score of pain during HSG,adverse reactions(allergic reaction of contrast medium,contrast medium reflux,etc.),24 h-peri-toneal distribution and natural pregnancy rate within 1 year after HSG were analyzed between the two groups.Results The VAS score[(1.62±0.92)points]and the incidence of contrast medium reflux(5.2％)in the ultra-liquefied ethiodized poppyseed oil-based con-trast medium group were lower than those in the iodized oil-based contrast medium group[(3.2±1.42)points and 13.8％],respectively and the differences between the two groups were statistically significant(P＜0.05).In the 24 h-peritoneal distribution,the diagnosis rate of mild pelvic adhesion in the ultra-liquefied ethiodized poppyseed oil-based contrast medium group(26％)was lower than that in the iodized oil-based contrast medium group(39.7％),and the difference was statistically significant(P=0.041).The natural pregnancy rate of the two groups within 1 year was significantly improved,but there was no significant difference between the two groups(P＞0.05).Conclusion Ultra-liquefied ethiodized poppyseed oil-based contrast medium has less pain,lower incidence adverse reactions and better peritoneal distribution,and improve the natural pregnancy rate in primary infertility patients undergoing HSG.It is a high priority contrast medium for HSG.

Due to the development of neonatal intensive care, the survival rate of very preterm infants and very low birth weight infants has been significantly improved, and the incidence of bronchopulmonary dysplasia (BPD) has been obviously increasing year by year.The pathogenesis of BPD has not been clear, it is considered that inflammation is an important link in the occurrence and development of BPD at present.Neutrophils can use their neutrophil extracellular traps (NETs) to capture and kill pathogens and reduce inflammation, but excessive formation of NETs is easy to induce inflammatory imbalance, so as to damage normal cells or tissues and participate in the pathophysiological process of BPD.This paper reviews the structure, formation, function and regulatory role of NETs in BPD, and the targeted treatment strategies and potential research directions of NETs in BPD.

Objective:To evaluate the effect of superior cervical ganglion block (SCGB) on cardiac function and nucleotide like receptor protein 3 (NLRP3) signaling pathway in a rat model of myocardial ischemia-reperfusion (I/R).Methods:Sixty healthy SPF male Sprague-Dawley rats, weighing 250-300 g, aged 2-3 months, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (sham group), myocardial I/R group (IR group), myocardial I/R + normal saline group (IR+ NS group), and myocardial I/R + SCGB group (IR+ SCGB group). Myocardial I/R model was developed by ligation of the left anterior descending branch of the coronary artery for 45 min followed by restoration of blood flow in anesthetized aninals. IR+ SCGB group received SCGB (0.25% ropivacaine 0.1 ml) at 10 min before reperfusion once a day for 2 consecutive weeks, while 0.9% sodium chloride was given instead of ropivacaine in IR+ NS group. Blood samples were collected at 24 h and 14 days of reperfusion for determination of serum concentrations of norepinephrine (NE), troponin T (TnT), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18) and IL-1β by enzyme-linked immunosorbent assay. Echocardiography was performed before ischemia and at 14 days of reperfusion, and left ventricular short axis shortening rate (FS), ejection fraction (EF), and cardiac output (CO) were measured. The rats were sacrificed at 14 days of reperfusion and the hearts were taken for determination of the contents of norepinephrine (NE) in myocardial tissues in the infarction area (by enzyme-linked immunosorbent assay), percentage of myocardial fibrosis area (by Masson staining), M1 macrophage marker CD68 + cell count in the infarction area (by immunohistochemical method), and expression of NLRP3 and gasdermin D (GSDMD) in myocardial tissues (by Western blot). Results:Compared with Sham group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly increased, the expression of NLRP3 and GSDMD in myocardial tissues was up-regulated, CD68 + cell count was increased, and EF, CO and FS were decreased in IR group ( P<0.05). Compared with IR group, the serum concentrations of TnT, TNF-α, IL-18 and IL-1β, percentage of myocardial fibrosis area, and NE levels in serum and myocardial tissues were significantly decreased, the expression of NLRP3 and GSDMD in myocardial tissues was down-regulated, CD68 + cell count was decreased, and EF, CO and FS were increased in IR+ SCGB group ( P<0.05), and no statistically significant changes were found in the parameters mentioned above in IR+ NS group ( P>0.05). Conclusions:SCGB can improve the cardiac function in a rat model of myocardial I/R, and the mechanism may be related to the inhibition of NLRP3 signaling pathway.

Objective: To evaluate the efficacy and safety of Qili Qiangxin Capsule (QLQXC) combined with western medicine in patients with ischemic cardiomyopathy (ICM) comorbid with heart failure (HF) for clinical application. Methods: We searched relevant references in Chinese databases including China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), Wanfang Database, and China Biology Medicine (CBM), as well as English databases including PubMed and Embase, from the foundation of the database to January 8, 2023, without language restrictions. All statistical analyses, including subgroup and sensitivity analyses, were performed using the Review Manager (version 5.4) and Stata (version 15.0). Results: QLQXC combined with western medicine significantly increased the endpoints of overall response rate (ORR) (P< 0.000 01), left ventricular ejection fraction (LVEF) (P< 0.000 01), the score of Minnesota Living with Heart Failure Questionnaire (MLHFQ) (P = 0.000 2), and 6-minute walking distance (6MWD) (P < 0.000 01), decreased left ventricular end-diastolic diameter (LVEDD) (P < 0.000 01), left ventricular end-systolic diameter (LVESD) (P = 0.03), and pro-brain natriuretic peptide (pro-BNP) (P < 0.000 01), and reduced the incidence of rehospitalization (P = 0.000 3) and adverse events (AEs) (P = 0.000 6) compared with those under the conventional western therapy alone. Nonetheless, no significant difference was observed in reducing the mortality between the QLQXC combined with western medicine group and the western medicine group (P = 0.30). Conclusion The combination therapy of QLQXC with western medicine can potentiate cardiac function and raise the quality of life in patients with ICM comorbid with HF.

ObjectiveTo screen and validate key enzyme genes affecting the polysaccharide content in different Polygonatum species and perform in-depth amino acid sequence analysis by transcriptomic analysis of P. zanlanscianense， P. kingianum， and P. cyrtonema rhizomes to enrich the transcriptome data of Polygonatum plants and provide references for polysaccharide biosynthesis mechanism and genetic improvement. MethodThe Polygonatum transcriptome was sequenced and analyzed using the Illumina NovaSeq high-throughput sequencing platform， and the differences in the transcriptomes of the three Polygonatum species were compared and according to the annotations of Nr， Gene Ontology （GO）， and Kyoto Encyclopedia of Genes and Genomes （KEGG） databases. The key enzymes in the polysaccharide metabolism pathway were screened， and the expression of key enzyme genes was clustered and correlated with the polysaccharide content. Finally， Real-time polymerase chain reaction （Real-time PCR） was performed to validate the eight key enzyme genes， and the key genes of polysaccharide biosynthesis were further screened for homologous gene sequence analysis in combination with sequencing results， followed by constructing phylogenetic trees， predicting motifs， conserved structural domains， protein sequence isoelectric points， and molecular weights， and constructing 3D protein structures by using homology modeling method. ResultThe annotation of the Nr database revealed that three Polygonatum species had the highest gene homology with Asparagus officinalis. GO database annotation results showed that three Polygonatum species differed significantly in binding， catalytic activity， metabolic processes， and cellular components， while the KEGG pathway annotation results indicated that three Polygonatum species differed significantly in the starch and sucrose metabolic pathway and galactose metabolic pathway. According to clustering analysis， correlation analysis， Real-time PCR， expression profiles， and structural and functional predictions of amino acid sequences， the key enzyme significantly affecting the polysaccharide content in different Polygonatum species was inferred to be β-fructofuranosidase （sacA）. ConclusionSacA may be the main influencing factor for the difference in polysaccharide content of Polygonatum， and is also an important reason why Polygonatum polysaccharides are mainly fructans.

INTRODUCTION: Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit. METHODS: This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m², and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test. RESULTS: A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE. CONCLUSION Serum NGAL identifies AKI and predicts three-month mortality.
Humans ; Lipocalin-2 ; Prospective Studies ; Lipocalins ; Proto-Oncogene Proteins ; Acute-Phase Proteins ; Biomarkers ; Acute Kidney Injury/diagnosis* ; Emergency Service, Hospital ; Predictive Value of Tests

Tyrosol is a natural polyphenolic product that is widely used in chemical, pharmaceutical and food industries. Currently, the de novo synthesis of tyrosol by Escherichia coli suffers from issues such as low cell density and poor yield. Therefore, the phenylpyruvate decarboxylase mutant ARO10^F138L/D218G obtained in our previous study was fused with an alcohol dehydrogenase from different microorganisms for fusion expression, and the optimal ARO^{10F138L/D218G}-L-YahK produced 1.09 g/L tyrosol in shake flasks. In order to further improve tyrosol production, feaB, a key gene in the competing pathway of 4-hydroxyphenylacetic acid, was knocked out, and the resulted strain produced 1.26 g/L tyrosol with an increase of 21.15% compared to that of the control. To overcome the low cell density in tyrosol fermentation, the quorum-sensing circuit was used to dynamically regulate the tyrosol synthesis pathway, so as to alleviate the toxic effect of tyrosol on chassis cells and relieve the growth inhibition. Using this strategy, the yield of tyrosol was increased to 1.74 g/L, a 33.82% increase. In a 2 L fermenter, the production of tyrosol in the engineered strain TRFQ5 dynamically regulated by quorum-sensing reached 4.22 g/L with an OD₆₀₀ of 42.88. Compared with those in the engineered strain TRF5 statically regulated by induced expression, the yield was increased by 38.58% and the OD₆₀₀ was enhanced by 43.62%. The combination of blocking the competing pathway using gene knockout technology, and reducing the inhibitory effect of tyrosol toxicity on chassis cells through quorum-sensing dynamic regulation increased the production of tyrosol. This study may facilitate the biosynthesis of other chemicals with high toxicity.
Escherichia coli/genetics* ; Biological Products ; Bioreactors ; Fermentation

OBJECTIVETo evaluate the diagnostic value of dynamic monitoring of C-reactive protein (CRP) in drainage fluid in predicting early anastomotic leakage after colorectal surgery.

METHODSThis study enrolled 172 patients, who were diagnosed as colorectal cancer before operation and underwent radical surgery, without residual tumor tissues by postoperative pathology and perioperative infection, at the Tianjin Medical University Cancer Hospital between July 2015 and January 2016. The C-reactive(CRP) protein level in drainage fluid was continuously monitored from postoperative days (POD) 1 to 5. CRP level was compared between anastomotic leakage (AL) group and non-anastomotic leakage (NAL) group. Receiver operating characteristics (ROC) curve was used to estimate the value of monitoring CRP in drainage fluid to predict anastomotic leakage after colorectal surgery.

RESULTSAmong 172 patients, 101 cases were male and 71 cases were female, with age of (59.9±10.3) years. Anastomotic leakage occurred after colorectal surgery in 24 cases(14.0%, AL group ) and other 148 cases were defined as NAL group. Other than body mass index (BMI), differences in baseline data were not statistically significant between two groups. The CRP lever in AL group and NAL group showed rising trend from POD1 to POD4 [Day 1: (6.7±8.4) g/L vs. (8.0±10.6) g/L; Day 2: (24.8±14.6) g/L vs. (28.3±21.1) g/L, Day 3: (54.8±26.5) g/L vs. (53.8±27.6)g/L, Day 4: (62.0±32.2) g/L vs. (58.4±30.7) g/L], while the differences were not significant (all P>0.05). At POD 5, the CRP lever of AL group increased continuously, while that of NAL group decreased with significant difference [(65.3±38.9) g/L vs. (44.7±39.5) g/L, t=-2.85, P=0.005]. Further stratification analysis on AL group revealed CRP level in early AL (AL occurrence POD 10) showed rising trend from POD 1 to 4, then decreased slightly at POD 5, but whose differences were not significant (all P>0.05). ROC curve was drawn with AL condition as state variables and CRP level as test variables. The AUC of POD 1 to 4 was 0.425, 0.487, 0.510, 0.522 respectively and the AUC of POD 5 was the largest, 0.657 (95%CI:0.537-0.777). The largest Youden Index was 0.274. The critical value of CRP was 27.15 g/L. When this value was used as the point of tangency to predict the occurrence of AL, the sensitivity was 87.5%, the specificity was 39.9%, positive predictive value was 19.1%, and negative predictive value was 95.2%.

CONCLUSIONContinuous increase of CRP level in abdominal drainage fluid from POD 1 to POD 5 indicates the occurrence of AL after colorectal cancer operation, especially the detection of CRP level at POD 5 is important.