Clinical-radiomics predictors to identify the suitability of transarterial chemoembolization treatment in intermediate-stage hepatocellular carcinoma:A multicenter study

Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.

Mesh erosion into the colon following repair of parastomal hernia: A case report

BACKGROUND In recent years,mesh has become a standard repair method for parastomal hernia surgery due to its low recurrence rate and low postoperative pain.However,using mesh to repair parastomal hernias also carries potential dangers.One of these dangers is mesh erosion,a rare but serious complication following hernia surgery,particularly parastomal hernia surgery,and has attracted the attention of surgeons in recent years.CASE SUMMARY Herein,we report the case of a 67-year-old woman with mesh erosion after parastomal hernia surgery.The patient,who underwent parastomal hernia repair surgery 3 years prior,presented to the surgery clinic with a complaint of chronic abdominal pain upon resuming defecation through the anus.Three months later,a portion of the mesh was excreted from the patient’s anus and was removed by a doctor.Imaging revealed that the patient’s colon had formed a t-branch tube structure,which was formed by the mesh erosion.The surgery reconstructed the structure of the colon and eliminated potential bowel perforation.CONCLUSION Surgeons should consider mesh erosion since it has an insidious development and is difficult to diagnose at the early stage.

Blue LED promotes the chemosensitivity of human hepatoma to Sorafenib by inducing DNA damage

Background:Phototherapies based on sunlight,infrared,ultraviolet,visible,and laser-based treatments present advantages like high curative effects,small invasion,and negligible adverse reactions in cancer treatment.We aimed to explore the potential therapeutic effects of blue light emitting diode(LED)in human hepatoma cells and decipher the underlying cellular and molecular mechanisms.Methods:Wound healing and transwell assays were employed to probe the inhibition of the invasion and migration of hepatocellular carcinoma cells in the presence of blue LED.The sphere-forming test was used to evaluate the effect of LED blue light irradiation on cancer stem cell properties.Immunofluorescence and western blotting were used to detect the changes inγ-H2AX.The Cell Counting Kit-8 assay,5-ethynyl-2′-deoxyuridine staining,and colony formation assay were used to detect the combined effect of blue LED and sorafenib on cell proliferation inhibition.Results:We demonstrated that the irradiation of blue LED light in hepatoma cells could lead to cell proliferation reduction along with the increase of cell apoptosis.Simultaneously,blue LED irradiation also markedly suppressed the migration and invasion ability of human hepatoma cells.Sphere formation analysis further revealed the decreased cancer stemness of hepatoma cells upon blue LED irradiation.Mechanistically,blue LED irradiation significantly promoted the expression of the phosphorylation of the core histone protein H2AX(γ-H2AX),a sensitive molecular marker of DNA damage.In addition,we found that the combined treatment of blue LED irradiation and sorafenib increased cancer cell sensitivity to sorafenib.Conclusion:Collectively,we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer cells by inducing DNA damage and could enhance chemosensitivity of cancer cells,which represents a potential approach for human hepatoma treatment.

Exploration of transmission chain and prevention of the recurrence of coronavirus disease 2019 in Heilongjiang Province due to inhospital transmission

The coronavirus disease 2019(COVID-19)epidemic is a major public health emergency characterized by fast spread,a wide range of infections,and enormous control difficulty.Since the end of December 2019,Wuhan has become the first core infection area of China's COVID-19 outbreak.Since March 2020,the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases.Herein,we reported the major COVID-19 outbreak,which caused a rebound of the epidemic in Harbin,China.After the rebound,different levels of causes for the recurrence of COVID-19,including citylevel,hospital-level,and medical staff-level cause,were investigated.Meanwhile,corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level,hospital level,and medical staff level,which eventually showed the effect of infection control function in a pandemic.In this study,we described the complete transmission chain,analyzed the causes of the outbreak,and proposed corresponding countermeasures from our practical clinical experience,which can be used as a valuable reference for COVID-19 control.

Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning:A case report

BACKGROUND The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit.The subsequent formation of methemoglobin(MetHb)restricts oxygen transport and utilization in the body,resulting in functional hypoxia at the tissue level.In clinical practice,a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia.Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions.CASE SUMMARY A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission.Subsequently,she developed vomiting and cyanotic skin.The woman underwent orotracheal intubation,invasive mechanical ventilation(IMV),and correction of internal environment disturbance in the ICU.Her premature infant was born with a higher-than-normal MetHb level of 3.3%,and received detoxification with methylene blue and vitamin C,supplemental vitamin K1,an infusion of fresh frozen plasma,as well as respiratory support via orotracheal intubation and IMV.On day 3 after admission,the puerpera regained consciousness,evacuated the IMV,and resumed enteral nutrition.She was then transferred to the maternity ward 24 h later.On day 7 after admission,the woman recovered and was discharged without any sequelae.CONCLUSION MetHb can cross through the placental barrier.Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.

Effect of cuproptosis on acute kidney injury after cardiopulmonary bypass in diabetic patients

BACKGROUND Cardiopulmonary bypass(CPB)is a common procedure in cardiac surgery.CPB is a high-risk factor for acute kidney injury(AKI),and diabetes is also such a factor.Diabetes can lead to copper overload.It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB.Levels of copper ion,lactate,glucose,heat shock protein-70(HSP-70),and dihydrolipoamide dehydrogenase(DLAT)were determined.A diabetic rat model was established and CPB was performed.The rats were assessed for the development of CPB-AKI,and for the association of AKI with cuproptosis by detecting copper levels,iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.RESULTS CPB resulted in elevations of copper,lactate,HSP-70 and DLAT in blood and urine in both diabetic and nondiabetic patients.CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats.Cuproptosis-related proteins also appeared to be significantly reduced.CONCLUSION CPB-AKI is associated with cuproptosis.Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

Puerarin modulation of CENPA affects downstream PLK1 and CCNB1 expression to inhibit bladder cancer cell proliferation

Background:The treatment alternatives for bladder cancer(BLCA),the 10th most prevalent cancer in the world,need to be further investigated,and many active substances like Puerarin in herbal medicine were found to be effective in treating BLCA.The purpose of this study was to investigate the potential treating mechanisms of Puerarin on BLCA.Methods:The cell counting kit 8 assay and flow cytometry were performed to confirm Puerarin’s ability to suppress BLCA.The differentially expressed proteins(DEPs)were obtained by Tandem Mass Tags technology and functional enrichment analysis performed by R studio.The most enriched pathways were selected for study and the DEPs were screened out.Protein-protein interaction network maps were created using String and Cytoscape and key proteins,which will be analyzed for survival,expression,and upstream transcription factor prediction,were screened out using the cytoHubba plugin.CHEA3 was used to obtain upstream transcription factor validated by molecular docking and western blotting experiments.Results:Cell counting kit 8 showed that Puerarin inhibited BLCA cells,with 50%inhibitory concentration of 218μmol/L in T24 and 198μmol/L in 5637.Flow cytometry reveals that Puerarin blocks T24 and 5637 cells in G1 phase.1,385 DEPs were obtained and the enrichment analysis revealed that cell cycle and DNA replication were the two main areas in which DEPs were enriched.Cyclin-B-cyclin dependent kinase 1(CDK1),cyclin B1(CCNB1),and polo-like kinase 1(PLK1)were identified as key proteins,and their upstream transcription factor was predicted to be centromere protein A(CENPA).Puerarin’s binding energy to CENPA was determined by molecular docking to be−6.3 kcal/mol,indicating a strong binding interaction.Western blot showed that Puerarin significantly reduced the expression of CENPA.Conclusion:We hypothesize that Puerarin may inhibit the proliferation of bladder cancer cells by inhibiting CENPA expression to regulate PLK1 and CCNB1 expression,thereby affecting cell cycle.

Molecular hydrogen regulates the expression of miR-9,miR-21 and miR-199 in LPS-activated retinal microglia cells

·AIM: To explore the potential mechanism of molecular hydrogen in the regulation of miRNA expression and signal-modulating activities. ·METHODS: Retinal microglia cells were activated by Lipopolysaccharides (LPS) and then treated with hydrogen -saturated medium or normal medium without hydrogen. qRT -PCR was used to detect the expression difference in miR-9, miR-21 and miR-199 between these two groups. Moreover, the expression of LPS -induced signaling proteins, including Myd88, IKK -β, NF -kB, and PDCD4, were detected by Western blotting. ·RESULTS: The results demonstrated a marked downregulation of miR -9 and miR -21 and up -regulation of miR-199 by hydrogen treatment; the expression of Myd88 and IKK-β was decreased after hydrogen treatment, whereas PDCD4 was increased, and there was no significant change in NF-kB expression. · CONCLUSION: The results in the present study indicate that miR -9, miR -199 and miR -21 play an important role in the anti -inflammatory regulation of LPS -activated microglia cells by molecular hydrogen, which will help to explain the protective mechanism of molecular hydrogen against inflammatory injury.·

Controversy over the use of intraoperative blood salvage autotransfusion during liver transplantation for hepatocellular carcinoma patients

Intraoperative blood salvage autotransfusion (IBSA) is used in various surgical procedures. However, because of the risk of reinfusion of salvaged blood contaminated by tumor cells, the use of IBSA in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is controversial. The critical points include whether tumor cells can be cleared by IBSA, whether IBSA increases the risk of recurrence or metastasis, and what are the indications for IBSA. Moreover, is it warranted to take the risk of tumor dissemination by using IBSA to avoid allogeneic blood transfusion? Do the remaining tumor cells after additional filtration by leukocyte depletion filters still possess potential tumorigenicity? Does IBSA always work well? We have reviewed the literature and tried to address these questions. The available data indicate that IBSA is safe in LT for HCC, but randomized, controlled and prospective trials are urgently required to clarify the uncertainty.

Adult reference values of the computerized diplopia test

AIM： To estimate the adult reference values for measured deviations by a computerized diplopia test and testify the validity.METHODS： Totally 391 participants were recruited and taken the computerized diplopia test. The plots and amplitude of deviations were recorded. The differences in different gender, age and visual acuity groups were analyzed respectively. Of 30 subjects were enrolled to testify the interobserver reliability. Another 46 subjects（including 26 normal subjects and 20 patients） were taken the test and theirs deviations were recorded to testify the validity of the reference value.RESULTS： The max horizontal and vertical deviations were 2.55° and 0.76° with normal corrected visual acuity while 3.88° and 1.46° for subjects with poor corrected vision. The differences between age groups was insignificant（Z =3.615, 4.758; P =0.461, 0.313 for horizontal and vertical respectively）. The max horizontal deviation of female was smaller than male（Z =-2.177; P =0.029）,but the difference in max vertical deviation was insignificant（Z =-1.296; P =0.195）. The mean difference between observers were both-0.1°, with 95% confidence limits（CI） of-1.4° and 1.6° in max horizontal deviations while-2.1° and 1.8° in max vertical deviation. The mean deviation of 26 normal subjects was 1.02° ±0.84° for horizontal and 0.47° ±0.30° for vertical which both within the range of reference values. The mean deviation of 20 patients was 13.51°±11.69° for horizontal and 8.34°±8.58°for vertical which both beyond the reference range.CONCLUSION： The max amplitude of horizontal and vertical deviation is pointed as the numerical parameters of computerized diplopia test. The reference values are different between normal corrected visual acuity and poor corrected vision. These values may useful for evaluating patients with diplopia in veriety conditions during clinical practice.

Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw(MRONJ)is a serious side effect of bone-modifying agents and inhibits angiogenesis agents.Although the pathogenesis of MRONJ is not entirely clear,multiple factors may be involved in specific microenvironments.The TGF-β1 signalling pathway may have a key role in the development of MRONJ.According to the clinical stage,multiple variables should be considered when selecting the most appropriate treatment.Therefore,the prevention and management of treatment of MRONJ should be conducted in patient-centred multidisciplinary team collaborative networks with oncologists,dentists and dental specialists.This would comprise a closed responsibility treatment loop with all benefits directed to the patient.Thus,in the present review,we aimed to summarise the pathogenesis,risk factors,imaging features,clinical staging,therapeutic methods,prevention and treatment strategies associated with MRONJ,which may provide a reference that can inform preventive strategies and improve the quality of life for patients in the future.

The Relationship between p38MAPK and Apoptosis during Paclitaxel Resistance of Ovarian Cancer Cells

To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration （IC50） of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RToPCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was （19.7±1.04）% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group （p〈0.05）. The relative reversal rate of A2780/Taxol cells to paclitaxel was （57.18±2.01）%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.

The balloon occlusion and thrombus aspiration catheter mediated-distal coronary perfusion technique(BI-RESCUE)for treatment of coronary artery perforation

Coronary artery perforation(CAP)remains an infrequent but potentially lifethreatening complication during percutaneous coronary intervention(PCI).Although the prevalence of CAP is about 0.2%−0.9%in relatively low risk PCI,the incidence could up to 9%in complex clinical scenarios such as severe coronary calcification,chronic total occlusions and rotational atherectomy.[1]Despite the new techniques and equipment had lower morbidity and mortality,up to 17%of acute CAP cases would evolve to tamponade and subsequent death.

Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth

FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam2OA-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM2OA. By breeding K14-Cre mice with Fam20An^x/fl^x mice, we created K14-Cre;Fam20Af/flox/flox （conditional knock out, cKO） mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X-ray radiography： histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam2OA-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice, The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues.

Targeting of p38 Mitogen-activated Protein Kinases to Early Growth Response gene 1 (EGR-1) in the Human Paclitaxel-resistance Ovarian Carcinoma Cells

To investigate the relationship between the expression of early growth response gene 1 （EGR-1） and p38MAPK pathway in the paclitaxel resistance of ovarian carcinoma cells, the effect of p38MAPK inhibitor SB203580 on cell apoptosis was examined by using Hoechst 33258 staining. The intracellular Rh123 （Rhodamine 123） accumulation was detected by the flow cytometry （FCM）. The 50% inhibition concentration （IC50） of paclitaxel for A2780/Taxol cells was determined by MTT method. Electrophoretic motility shift assay （EMSA） was employed to examine the EGR-1DNA binding activity. MDR1 and EGR-1 mRNA were assessed by RT-PCR. The expressed of p-gp, phos- phorylated p53 and p38 were detected by Western blotting. SB203580 could remarkably promote the apoptosis of A2780/Taxol cells, and the cell apoptosis was in a time-dependent manner. Cellular Rh123 accumulation was increased, and the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly. A2780/Taxol cell line after SB203580 treatment was shown to have a significantly higher level of EGR-1 DNA binding activity. SB203580 down-regulated the activity of p38MAPK pathway, but up-regulated EGR-1 expression. SB203580 significantly increased the level of cellular phosphorylated p53 protein, but decreased the p-gp protein level and MDR1 mRNA level in A2780/Taxol cells. There existed a close relationship between p38MAPK pathway and the paclitaxel resistance of ovarian carcinoma cells. The expression of EGR-1 mediated by p38MAPK pathway plays a critical role in paclitaxel resistance of ovarian carcinoma cells.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Management of procedural pain in the intensive care unit

Pain is a common experience for inpatients,and intensive care unit(ICU)patients undergo more pain than other departmental patients,with an incidence of 50%at rest and up to 80%during common care procedures.At present,the management of persistent pain in ICU patients has attracted considerable attention,and there are many related clinical studies and guidelines.However,the management of transient pain caused by certain ICU procedures has not received sufficient attention.We reviewed the different management strategies for procedural pain in the ICU and reached a conclusion.Pain management is a process of continuous quality improvement that requires multidisciplinary team cooperation,painrelated training of all relevant personnel,effective relief of all kinds of pain,and improvement of patients'quality of life.In clinical work,which involves complex and diverse patients,we should pay attention to the following points for procedural pain:(1)Consider not only the patient's persistent pain but also his or her procedural pain;(2)Conduct multimodal pain management;(3)Provide combined sedation on the basis of pain management;and(4)Perform individualized pain management.Until now,the pain management of procedural pain in the ICU has not attracted extensive attention.Therefore,we expect additional studies to solve the existing problems of procedural pain management in the ICU.

Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells

We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.

Removal of refractory thrombus by 5F child catheter in patients with subacute myocardial infarction

No-reflow phenomenon is common in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI),and it is strongly associated with adverse clinical prognosis.Previous studies have shown that heavy thrombus burden could predict the development of no-reflow in PCI.Manual and mechanical thrombus aspiration catheters are widely used;however,there is still residual refractory thrombus left after the routine use of thrombectomy,especially in patients with subacute myocardial infarction(SMI).In our practice,child catheter aspiration has been used as a safe and effective approach to solve the residual thrombus in SMI patients.We described this technique in detail by a series of cases.