OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

The aim of this study was to investigate the effect and mechanisms of miR-29a in migration and inva-sion of human breast cancer MCF-7 cells in vitro. MCF-7 cells were treated with miR-29a mimic or miR-29a inhibitor to up-regulate/down-regulate the expression level of miR-29a. Wound-healing assay and transwell chamber were employed to determine cell migration and invasion in vitro. The target gene of miR-29a was predic-ted with the Targetscan7. 1 database and verified through luciferase reporter method. The effects of miR-29a on the expression of the potential target were detected by Western blot and real-time PCR. Results showed that in vitro migration and invasion ability of MCF-7 cells was increased significantly by miR-29a,which could target HBP1 in the 3′-UTR region. The protein expression of HBP1 was decreased by miR-29a overexpression. However, the alteration of miR-29a had no significant effect on the expression of HBP1 mRNA. The results validated that miR-29a,highly expressed in breast cancer,could down-regulate HBP1 ,which in turn promotes migration and invasion ability of breast cancer cells,thus promoting breast cancer metastasis.

Objective To evaluate the diagnostic performance of the automated quantitative analysis by coronary computed tomography angiography (CCTA) for lesion specific hemodynamic significance assessed by fractional flow reserve(FFR). Methods One hundred and fifteen patients with one hundred and fifty?one vessels,who successively underwent invasive coronary angiography with evaluation of FFR(values≤0.8 were defined as lesion specific hemodynamically significant), were analyzed by coronary CT angiography. FFR≤0.80 was found in 54(35.76％) of the 151 vessels, which was divided into two groups (group of hemodynamically significant and group of hemodynamically non-significant). CCTA images were quantitatively analyzed with automated software to obtain the following index:minimal lumen diameter(MLD), maximum diameter stenosis(MDS％), minimal lumen area(MLA), maximum area stenosis(MAS％), lesion length (LL), total plaque volume(TPV), total plaque burden(TPB), calcified plaque volume(CPV), calcified plaque burden (CPB), non-calcified plaque volume(NCPV), non-calcified plaque burden(NCPB), lipid plaque volume(LPV), lipid plaque burden(LPB), fibrous plaque volume(FPV), fibrous plaque burden(FPB), napkin-ring sign(NRS), remodeling index(RI) and eccentric index(EI). Logistic regression and area under the receiver operating characteristics were used for statistical analysis. Results MDS％(65.04％± 8.20％), MAS％(73.91％± 7.58％), TPB(57.96％± 11.17％), CPB[4.32％(0.11％, 5.34％)], LPB[14.89％(9.30％, 19.23％)], CPV[30.68 (0.29, 33.36)mm3], LPV[(81.72(33.92, 94.68)mm3]in the group with hemodynamic significance were larger than those in group with normal hemodynamic status[58.27％± 9.50％, 64.83％± 8.31％, 53.88％± 11.77％, 2.05％(0.00％, 3.42％), 11.83％(6.34％, 16.8％), 12.53(0.00, 13.24)mm3, 60.71(24.1, 75.11)mm3, respectively], which was statistically significant(t=4.41,P<0.01;Z=6.63,P<0.01;t=2.08,P<0.05;Z=-2.47,P<0.01;Z=-2.30,P<0.05;Z=-2.48, P<0.01;Z=-2.55, P<0.01, respectively). MLD[1.24(1.04, 1.46)mm]and MLA[3.61(2.40, 4.80) mm2]in the group with hemodynamic significance were smaller than those in group with normal hemodynamic status[1.53(1.32,1.72)mm, 5.28(4.00,6.40)mm2],which was statistically significant[Z=-4.82,-5.40, respectively;P<0.01].In logistic regression analysis, only MAS％(OR:1.08,95％CI:1.01-1.15,P=0.02), CPB (OR:1.16,95％CI:1.02-1.33,P=0.02) and LPB(OR:1.10,95％CI:1.01-1.19,P=0.02), MLA(OR:0.69, 95％CI:0.49-0.98,P=0.04)were significant predictors of hemodynamic significance. For predicting lesion specific hemodynamic significance, compared with MLA(0.76), MDS％(0.71), CPB(0.62) and LPB(0.61), except for MLA(Z=0.77, P=0.44), the AUC of MAS％(0.79) was significantly increased(Z=2.54, P=0.01;Z=2.91, P<0.01;Z=2.94, P<0.01, respectively). However, combination of other index to MAS％[MAS％+MLA％(0.81), MAS％+MDS％(0.80), MAS％+TPB(0.80), MAS％+CPB(0.80), MAS％+LPB(0.81)] did not show significantly difference over MAS％(Z=1.10, 0.71, 0.40, 0.54, 1.07, respectively;P>0.05). Conclusion Compared with diameter stenosis, area stenosis substantially improves the prediction of lesion specific hemodynamic significance.

Objective To investigate the relationship between white-matter hyperintensities (WMHs) and hemorrhagic transformation and neurological outcome at 3 months after recombinant tissue plasminogen activator (rt-PA) treatment in patients with acute ischemic stroke.Methods The chnical data of 132 patients with acute ischemic stroke who had received intravenous rt-PA therapy were retrospectively reviewed.The severity of WMHs according to the modified Schelten scale was assessed.Hemorrhagic transformation included hemorrhagic infarct (HI) and cerebral parenchymal hemorrhage (PH).Hemorrhagic transformation after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months was also analyzed.Favorable neurological outcome as mRS 0-1 score and unfavorable neurological outcome as mRS 2-6 scores was defined.Results Hemorrhagic transformation was found in 26 patients (19.7％,26/132) among 132 patients receiving intravenous rt-PA treatment.Seventeen patients were HI type and 9 patients were PH type.Multiple Logistic regression analysis showed that baseline American National Institute of Health Stroke Scale (NIHSS) score,diastolic pressure,WMHs score was not correlated with HI type hemorrhagic transformation (P ＞ 0.05) ; and WMHs score was not correlated with PH type hemorrhagic transformation (P ＞0.05),but baseline NIHSS score,diastolic pressure was the independent risk factor of PH type hemorrhagic transformation (P ＜ 0.05).Dicho-Logistic regression analysis showed that WMHs score was the independent risk factor of unfavorable neurological outcome (OR =1.136,95％ CI 1.037-1.245,P =0.008).Conclusion Severe WMHs are not associated with hemorrhagic transformation but independently associated with unfavorable neurological outcome after thrombolytic therapy in patients with acute ischemic stroke.

Objeetive To explore the correlative factors of early progressive motor deficits in cerebral infarction of moderately size in basal ganglia and the relationship between motor deficit progression and the stem lesion of middle cerebral artery.Methods One hundred and fifty patients with single acute infarction located in white matter of basal ganglia region were recruited in this study retrospectively.All patients were performed brain and neck MRI and magnetic resonance angiography (MRA) within 72 h after onset.They were divided into two groups based on the maximal diameter of infarction on diffuse weighing imaging(DWI):moderate size infarction group(75 patients,maximal diameter of infarction from 1.5 cm to 3.0 cm) and lacunar infarction group(75 patients,maximal diameter of infarction lower than 1.5 cm).The scores of dynamic National Institutes of Health Stroke Scale(NIHSS) in 7 d after the admission and multiple Logistic regression analysis were used and the risk factors of the early progressive motor deficits were analyzed.Results The rate of early progressive motor deficits in moderate size infarction group was significant higher than that in lacunar infarction group [32.0 ％ (24/75) vs.8.0 ％ (6f75)] (P ＜ 0.05).The multiple Logistic regression analysis showed that elevated systolic blood pressure on admission was the independent risk factor for early progressive motor deficits (P =0.016).The rate of stem lesion of middle cerebral artery in moderate size infarction group was significantly higher than that in lacunar infarction group [41.3 ％ (31/75) vs.9.3 ％ (7/75)] (P ＜ 0.01).Conclusions Patients with acute single infarction located in white matter of basal ganglia and with the diameter of 1.5-3.0 cm are more prone to early progressive motor deficits and elevated systolic blood pressure on admission is the most significantly independent factor.The pathogenic mechanism may be associated with the stem lesion of middle cerebral artery.

BACKGROUND: Following trauma caused by seawater, cells often exhibit special pathological changes because of the special physico-chemical properties of seawater.OBJECTIVE: To observe corneal histopathological changes and interleukin-6 level in aqueous humor of a rabbit model of penetrating corneal trauma combined with seawater immersion.METHODS: The rabbit eye models of penetrating corneal trauma caused by firecrackers were established in 16 adult healthy grey rabbits. A 3-mm whole-layer incision was made in the cornea. The right eyes served as experimental sides and the left eyes served as controls. Seawater was injected into the aqueous humor of the right eyes via the corneal incision. The eye surface was flushed with seawater for 30 minutes. Physiological saline was used for the left eyes. RESULTS AND CONCLUSION: Optical microscopy results showed that at 1, 2, 3 days after model establishment, corneal cells on the experimental side exhibited severe necrosis and abscission, obvious swelling of substantia propria layer complicated by cellular infiltration. At 1 and 2 days after model establishment, the pathological changes on the control side were the same as the experimental side, but they were mild, but at 3 and 5 days, they were obviously alleviated. At 1, 2, 3 days after model establishment, interleukin-6 level in aqueous humor was significantly higher on the experimental side than on the control side (P < 0.05). These findings suggest that the degree of injury on the experimental side was more severe than that on the control side, indicating that seawater may be an important causative factor of corneal injury.

BACKGROUND:The safety and efficacy of paclitaxel-eluting stents (Taxus DES) has been proved by international researchers in clinic investigations.Based on further inclusion criteria,the incidence of in-stent restenosis is still lower than that of bare-metal stent.OBJECTIVE:TO observe restenosis of Taxus DES and the effect on local vessels through applying the follow up of coronary angiography and to investigate the biocompatibility of stent and host.DESIGN:Following-up observation.SETTING:Department of Cardiology,General Hospital of Chinese PLA.PARTICIPANTS:A total of 297 patients who had undergone coronary Taxus DES implantation for coronary artery disease were selected from Cardiovascular Department of General Hospital of Chinese PLA from May 2003 to May 2005.There were 265 males and 32 females and their ages ranged from 36 to 76 years.All patients provided informed consent,and the experiment had got confirmed consent from local ethic committee.METHODS:All patients were implanted Taxus DES and received the follow up within 6 and 12 months.In addition,at 6 months after operation,coronary angiography was used to measure the reference vessel diameter (RVD) and the minimal lumen diameter(MLD),calculate diameter restenosis rate and observe late loss.MAIN OUTCOME MEASURES:Coronary angiography at 6 months after Taxus DES implantation and biocompatibility of stent and host.RESULTS:①Quantitative angiographic analysis(QCA):Angiographic follow-up showed that the late loss of in-stent was significantly higher than that of pro-in-lesion and dis-in-lesion(P＜0.05).②Coronary angiography in-stent restenosis:In 134 angiographic follow-up patients,a total of 14 patients experienced restenosis,and the incidence was 10.4%(14/134).The patterns of restenosis were diffuse in-stent in 7 patients and the rate of revascularization was 6.7%.③Stent aneurysm:Angiographic evidence of aneurysm was observed in one patient among follow-up cases,and the rate of which was 0.75% (1/134).④Clinic follow-up major adverse cardiac events(MACE):Among 297 patients,one patient was attracted sudden death 5 months after intervention (0.34%; 1/297),and one patient was suffered subacute thrombosis 5 days after stent implant (0.34%;1/297),and late thrombosis occurred in 2 patients.The general rate of MACE was 1.35%.CONCLUSION:①The late loss of Taxus DES mainly takes place in in-stent.The patterns of restenosis of Taxus DES are in majority of diffuse in-stent,and the incidence of MACE is low.②Taxus DES possibly results aneurysm in local vessels.The follow up indicates that Taxus DES has a good biocompatibility to patients.