Objective To investigate the prognostic value of plasma thrombomodulin(TM)in patients with septic shock.Methods A retrospective analysis was conducted on the clinical data of 180 patients with septic shock admitted to the intensive care unit of the 908th Hospital from May 2018 to November 2022.The patients were divided into survival group(106 cases)and death group(74 ca-ses)based on the 30-day follow-up outcomes.Propensity score matching(PSM)was used to match 57 surviving patients with 57 de-ceased patients in a 1∶1 ratio,based on confounding factors such as age,gender,underlying diseases,primary infection site,laborato-ry results and disease severity scores.TM and other coagulation molecular markers were compared between the two groups,and logistic regression,receiver operating characteristic(ROC)curve,survival and correlation analyses were performed.Results After PSM,the TM levels in the death group(18.3[13.2,22.3]TU/mL)were significantly higher than those in the survival group(13.7[9.0,18.3]TU/mL)(P＜0.05).Multivariate logistic regression analysis showed that TM was an independent risk factor for 30-day mortality in the patients with septic shock(OR=1.137,95％CI:1.023-1.262,P＜0.005).ROC curve analysis revealed that the areas under the curve(AUCs)for predicting 30-day mortality were 0.665,0.627 and 0.600 for TM,Acute Physiology and Chronic Health EvaluationⅡ(APACHE Ⅱ)and Sequential Organ Failure Assessment(SOFA)scores,respectively.Kaplan-Meier survival analysis stratified by the optimal TM cut-off value(17.9 TU/mL)showed that the 30-day survival rate of the TM＜17.9 TU/mL group was 1.56 times that of the TM≥17.9 TU/mL group(Log-Rank test,P＜0.000 1).Spearman correlation analysis demonstrated that TM levels were positively correlated with APACHE Ⅱ(r=0.10,P＜0.005)and SOFA scores(r=0.35,P＜0.005).Conclusion Plasma TM has showed a good predictive value for assessing the prognosis of patients with septic shock and may serve as a potential biomarker for determining the prognosis of septic shock.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Purpose: Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. Results: We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. Conclusion Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

OBJECTIVE：To excavate the safety warning signals induced by azole antifungal agents ，including fluconazole ， ketoconazole，itraconazole and voriconazole after marketing ，and to provide references for rational drug use in the clinic. METHODS：Reporting odds ratio （ROR）data mining algorithm was used to investigate signals of adverse drug event （ADE）for fluconazole，ketoconazole，itraconazole and voriconazole from FDA Adverse Event Reporting System （FAERS）during January 1st，2004 to March 30th，2019. ROR data mining method was used to excavate the ADR signals of the drugs ，and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS ：A total of 27 831，5 712， 5 381 and 11 333 reports were picked out for fluconazole ，ketoconazole，itraconazole and voriconazole ，respectively. All of these drugs had exhibited high-risk signals detection by ROR ，including medical examination ，blood and lymphatic system disorders ， renal and urinary disorders ，endocrine diseases ，hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole （fluconazole ROR ＝6.51，voriconazole ROR ＝14.65）；ADR detection results of Cushing’s-like syndrome （ROR＝24.86） and adrenal suppression （ROR＝44.06） by itraconazole showed high-risk signals ； ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction （ketoconazole ROR ＝15.64， itraconazole ROR ＝23.26），and the signal intensity of ketoconazole （ROR＝2.81）in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ，hemorrhagic cystitis caused by fluconazole，itraconazole and voriconazole were not included in the drug instructions （fluconazole ROR ＝17.73，itraconazole ROR ＝31.43，voriconazole ROR ＝17.06）； netted green spot caused by fluconazole （ROR＝10.50）were not included in the drug instructions . CONCLUSIONS：Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ，ketoconazole，itraconazole and voriconazole ； particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole，itraconazole，voriconazole and netted green spot caused by fluconazole ，as well as ADRs mentioned in the drug instructions but have abnormally high signal ，such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .

Objective To study the inhibitory effect and mechanism of dipeptide peptidase inhibitors analogues on LPS -induced inflam-matory response on microglia .Methods Microglia cells were cultured ,isolated and purified from the neonatal Sprague-Dawley rats.Divided them into blank group ,negative control ,LPS group and medicine group ( parallel determination for 3 times each group ) after pharmacological preconditioning for 48 hours.The optimal concentration of microglia proliferation induced by LPS were measured by MTT assay .Observed the role of dipeptide peptidase inhibitors analogues on LPS-induced microglia in different concentrations .The interleukin1β( IL-1β) ,tumor necro-sis factor alpha ( TNF-α) were assayed by enzyme-linked immunorrbent assay ( ELISA ) .The expression of TLR-4 was detected by Western blotting and the expression of NF-κB was detected by RT-PCR.Results LPS induced the proliferation of microglia and significantly in-creased the release of inflammatory cytokines in LPS-stimulated primary microglia .Compared with the blank group ,dipeptide peptidase inhibi-tors analogues could inhibit this effect and the IC 50 values was 1.014 ×10 -2 mol/L to MG after pretreatment for 48 hours.Dipeptide peptidase inhibitors analogues could inhibit the release of TNF-αand IL-1 significantly(P<0.01),and it decreased the expression of TLR4 and NF-κB signif-icantly(P<0.01).Conclusion This research suggests that dipeptide peptidase inhibitors analogues restrain cell proliferation and inflammatory re-sponse of LPS-stimulated microglia,and the possible mechanism may be related to the inhibition of the expression of TLR-4 and NF-κB.

Objective To investigate the clinical application and effect of pick-stab skill in eyebrow embroidery.Methods From July 2015 to January 2016,36 cases were selected to receive eyebrow embroidery with pick-stab skill in our department,including 1 male and 35 females.The cosmetic outcomes,complications and satisfaction rate were observed in these cases.Results In these 36 cases,14 cases were colored in one time,19 cases were colored twice,and 3 cases were more than 3 times.All patients were followed up for 6 months.The color of the eyebrow was natural,and the blue color was not existed.Conclusions The pick-stab skill in eyebrow embroidery is worthy in clinic with better cosmetic effect,higher success rate and safety.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

ABSTRACT:In recent years ,there has been high prevalence of murine typhus in Yunnan Province ,People's Republic of China .A large outbreak of murine typhus occurred in Xishuangbanna Prefecture ,Yunnan Province in 2010 .However ,not all cases were confirmed by laboratory assays ;therefore ,field epidemiologic and laboratory investigations of murine typhus in Xishuangbanna Prefecture were conducted in 2011 .Blood samples were collected from clinical diagnostic cases at the acute and convalescence stages of murine typhus in Xishuangbanna Prefecture ,Yunnan Province ,from June to September of 2011 ,and blood and spleen samples were collected from mice sharing the same habitats as the patients .Immunofluorescence assays were used to test for the presence of IgM and IgG antibodies against Rickettsia typhi in sera from patients and mice .Real‐time PCR was used to detect the groEL gene of R .typhi in blood clots from patients at the acute stage and in spleen tissue from mice .A total of 1 157 clinically diagnosed murine typhus cases occurred in Xishuangbanna Prefecture ,Yunnan Province in 2011 ,with an incidence of 102 .10/100 000 .Of these cases ,80 were investigated by laboratory assays and 74 of 80 patients were confirmed to have murine typhus .The coincidence rate between the clinical diagnosis and laboratory detection was 92 .50% .The positivi‐ty rate for IgG antibodies against R .typhi was 14 .0% (14/100) for Rattus f lavipectus ,while the rate by PCR was 9 .0%(9/100) .That laboratory diagnoses confirmed that the severity of the murine typhus outbreak in Xishuangbanna cannot be ig‐nored .The distribution of host animals transmitting R .typhi underscores this conclusion .

Objective To investigate the influence of arsenic trioxide (AS2 O3 )in the vasculogenic mimicry (VM ) of HepG2 cells, and to preliminary clarify the possible mechanism of inhibition of AS2 O3 on the VM. Methods Themean inhibitory concentration (IC50 )of AS2 O3 72 h after treatment of HepG2 cells was calculated by CCK-8 assay.The HepG2 cells were cultured on 3-D Matrigel and randomly divided into control group, 1/2 IC50 AS2 O3 group and IC50 AS2 O3 group.IPP software was used to calculate the number,length and area of VM,and the expression levels of VM-related proteins VE-cadherin and MMP-2, apoptotic-related protein caspase-3 and proliferation-related protein PCNA were detected by Western blotting method.Results The IC50 of AS2 O3 was 10μmol·L-1 72 h after treatment of HepG2 cells.The number,length and area of VM in 1/2 IC50 and IC50 AS2 O3 groups were significantly lower than those in control group (P<0.01);the number,length and area of VM in IC50 AS2 O3 group were also lower than those in 1/2 IC50 AS2 O3 group (P<0.05).Compared with control group,the expression levels of VE-cadherin and MMP-2 in 1/2 IC50 and IC50 AS2 O3 groups were decreased (P<0.05),and the expression levels of caspase-3 and PCNA had no significant change (P>0.05).Conclusion AS2 O3 can inhibit the forming of VM of HepG2 cells,which indicated that its mechanism may be related to inhibiting the expressions of VE-cadherin and MMP-2 .