Clinical significance of expression of tissue factor and tissue factor pathway inhibitor in ulcerative colitis

AIM: To investigate the clinical significance of expression of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in ulcerative colitis (UC).

New Insights into the Discovery of Novel Drugs to Treat Human Pulmonary Adenocarcinoma

Lung cancer is one of the most prevalent cancers in the world. A cisplatin-based chemotherapy regimen is commonly used to major patients who have adenocarcinoma. Because of the limited remission rate, many patients need receive second-line treatment after receiving first-line chemotherapy. Drug screenings carried out currently are mainly from single phase. In consideration of systemic treatment, evaluation of a novel drug candidate from the point of view of first-line and second-line treatment is supposed to be important in the process of drug screening. In this review, we propose a flow of searching for new drugs, which is tailored to accommodate to first-line and second-line treatment in clinic.

Using shape-memory alloy staples to treat comminuted manubrium sterni fractures: A case report

BACKGROUND Comminuted manubrium sterni fractures are rare,and internal fixation methods are limited.This report explored a practical and feasible method of internal fixation for comminuted manubrium sterni fractures.CASE SUMMARY A 17-year-old female was injured in a car accident for which she underwent debridement and suturing of her head and anterior chest wounds in another hospital.Eight days later,the patient was transferred to our hospital for surgical treatment.The manubrium sterni was found intraoperatively to be split into three irregular fragments with obvious overlap and separation displacement.Meanwhile,a manubriosternal joint dislocation and left first rib cartilage fracture were observed.The retraction force of the shape-memory alloy staples was used to pull the fracture fragments together.Two more titanium locking plates were then used to fix the manubrium sterni and corpus sterni longitudinally,and the left first rib cartilage fracture was repositioned and fixed with a titanium locking plate.A postoperative computed tomography scan showed reduced and rigid fixation of the comminuted manubrium sterni fractures.The patient recovered well with no significant complaints of discomfort.The patient was discharged 10 days postoperatively after the stitches had been removed.CONCLUSION Shape-memory alloy staples had the advantage of being safe and effective during the repositioning and internal fixation of comminuted manubrium sterni fractures.Therefore,they provided a new surgical option for comminuted manubrium sterni fractures.

Reflection on the cognitive differences between doctors and patients

As we all know, the doctor-patient relationship in China is in a very tense state. There are many reasons for this situation, an important factor among them is the cognitive differences between doctors and patients.Here we analyze the reasons for the cognitive differences between doctors and patients from the perspective of both doctors and patients cognition of diseases, the motives of both parties and the expectations of curing diseases.We will also discuss a: "patient-centered" concept, strengthening effective communication between doctors and patients, as well as how they can respect each other's personality and rights.

Application of medial column classification in treatment of intraarticular calcaneal fractures

BACKGROUND There are many types of treatments for calcaneal fractures,including conservative treatment,conventional surgical treatment,and minimally invasive surgery.The choice of specific treatment options is still controversial.Open reduction and internal fixation are currently the most commonly used surgical procedures in the clinic.A good fracture reduction effect can be achieved by using the lateral extension incision of the calcaneus;however,many studies have reported a high incidence of postoperative incision complications.Although there are many methods for the classification of intra-articular calcaneal fractures,it is generally believed that the computed tomography(CT)classification proposed by Sanders has high application value in the selection of treatment methods and evaluation of prognosis of calcaneal fractures.However,this method has no clear guiding significance for the choice of surgical incision and surgical plan.AIM To explore the application and clinical efficacy of medial column classification in the treatment of intra-articular calcaneal fractures.METHODS From July 2017 to July 2018,91 patients,including 60 males and 31 females aged 27 to 60 years,were enrolled.All participants had closed intra-articular calcaneal fracture,and their surgical options were selected under the guidance of medial column classification.The patients'fractures were classified according to the Sanders classification:Type II,35 cases;Type III,33 cases;and Type IV,23 cases.Among them,53 patients had medial column displacement(shortened varus)and underwent open reduction and internal fixation with L-lateral incision of the calcaneus;38 patients had no displacement of the medial column and underwent open reduction and internal fixation with tarsal sinus incision.The calcaneus Bohler angle,Gissane angle,length,width,height,and step thickness of the articular surface were evaluated by X-ray and three-dimensional CT before and after surgery and at the last follow-up.Foot function recovery was assessed by the Maryland foot scoring criteria.RESULTS All patients were followed for 5 to 14 mo,with an average of 10.5±2.9 mo.The fractures of all patients healed,and the healing time was 10 to 19 wk,with an average of 10.8±1.5 wk.One patient developed wound infection 1 wk after surgery and was actively debrided and implanted with antibiotic calcium sulfate to control the infection.The patient's fracture healed 5 mo after surgery.One patient developed a sural nerve injury,and the symptoms disappeared 3 mo after surgery.The patients were assessed according to the Maryland foot scoring system:Excellent in 77 cases,good in 10,and fair in 4.The excellent and good rate was 95.6%.CONCLUSION Medial column classification can effectively guide the surgical selection for intraarticular fractures of the calcaneus.

Clinical study on the surgical treatment of atypical Lisfranc joint complex injury

BACKGROUND Lisfranc injuries have not received much attention by orthopedic doctors in the past,and there is little related research on the diagnosis and treatment of these injuries.In recent years with the rise in foot and ankle surgery,doctors are now paying more attention to this type of injury.However,there is still a high rate of missed diagnosis due to insufficient attention causing treatment delays or inadequate treatments,which eventually result in greater sequelae;including long-term pain,arthritis,foot deformity etc.In particular,for cases with a mild Lisfranc joint complex injury,the incidence of sequelae is higher.AIM To select an active surgical treatment for an atypical Lisfranc joint complex injury and to evaluate the clinical efficacy of the surgical treatment.METHODS The clinical data of 18 patients,including 10 males and 8 females aged 20-64 years with Lisfranc injuries treated in our department from January 2017 to September 2019 were retrospectively analyzed.All patients were treated with an open reduction and internal fixation method using locking titanium mini-plates and hollow screws or Kirschner wires.X-ray images were taken and follow-up was performed monthly after the operation;the internal fixation was then removed 4-5 mo after the operation;and the American Orthopedic Foot and Ankle Society(AOFAS)score was used for evaluation on the last follow-up.RESULTS All patients were followed up for 6-12 mo.A good/excellent AOFAS score was observed in 88.9%of patients.CONCLUSION For atypical Lisfranc joint complex injuries,active open reduction and internal fixation can be performed to enable patients to obtain a good prognosis and satisfactory functional recovery.

Clinicopathological significance of human leukocyte antigen F-associated transcript 10 expression in colorectal cancer

BACKGROUND Colorectal cancer(CRC) is a common malignancy of the gastrointestinal tract. The worldwide mortality rate of CRC is about one half of its morbidity. Ubiquitin is a key regulatory factor in the cell cycle and widely exists in eukaryotes. Human leukocyte antigen F-associated transcript 10(FAT10), known as diubiquitin, is an 18 kDa protein with 29% and 36% homology with the N and C termini of ubiquitin. The function of FAT10 has not been fully elucidated, and some studies have shown that it plays an important role in various cell processes.AIM To examine FAT10 expression and to analyze the relationship between FAT10 expression and the clinicopathological parameters of CRC.METHODS FAT10 expression in 61 cases of CRC and para-cancer colorectal tissues was measured by immunohistochemistry and Western blotting. The relationship between FAT10 expression and clinicopathological parameters of CRC was statistically analyzed.RESULTS Immunohistochemical analysis showed that the positive rate of FAT10 expression in CRC(63.93%) was significantly higher than that in tumor-adjacent tissues(9.84%, P < 0.05) and normal colorectal mucosal tissue(1.64%, P < 0.05). Western blotting also indicated that FAT10 expression was significantly higher in CRC than in tumor-adjacent tissue(P < 0.05). FAT10 expression was closely associated with clinical stage and lymphatic spread of CRC. FAT10 expression also positively correlated with p53 expression.CONCLUSION FAT10 expression is highly upregulated in CRC. FAT10 expression is closely associated with clinical stage and lymphatic spread of CRC.

Short-term clinical efficacy of capecitabine combined with oxaliplatin in the treatment of stage Ⅱ and Ⅲ rectal cancer after operation with Shengmai Yin

[Objective]To observe the short-term clinical efficacy of ciprofloxacin+oxaliplatin combined with Shengmaiyin onⅡ/Ⅲrectal cancer patients.[Method]120(2011.2-2018.2,Department of Surgical oncology,The Center Hospital Affiliated to Shenyang Medical College)Ⅱ/Ⅲrectal cancer patients,then they were randomly divided into control group and observation group,every group include 60 patients.The control group were given ciprofloxacin+oxaliplatin,and the three-dimensional conformal radiotherapy,observation group were given Shengmaiyin,treatment for 1 month,then assessed the clinical efficacy,the immunidy index(cellular immunity and humoral immunity),and record the adverse reaction.[Results]After treatment,short term clinical efficacy in observation group significantly better than the control group but the difference had no statistical significance(p>0.05).After treatment,the immunidy index(cellular immunity and humoral immunity)in the two groups were better than before treatment,the difference had statistical significance(p<0.05),and the observation group were better than control group,the difference had statistical significance(p<0.05).During the treatment,reducing leucocyte and platelet,nausea,vomit,etc were appearring in both groups,the clinical in the observation group was better than control group(94.00%vs 90.91%),but the difference had no statistical significance(P>0.05).[Conclusions]Using the ciprofloxacin+oxaliplatin combined with Shengmaiyin onⅡ/Ⅲrectal cancer patients treatment can improve the immunidy function and short-term clinical efficacy.

Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection

Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.

Correction to:Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection

The information of affiliation 1 and 3 was incorrect.The information of affiliations should read as given below.Author information 1 Virology Lab,Shengjing Hospital of China Medical University,Shenyang 110004,China 2 Department of Laboratory,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024,China.

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke:subgroup analysis of the TRACE-2 randomised controlled clinical trial

Background The benefit of intravenous alteplase in acute ischaemic stroke(AIS)is time-­dependent.Tenecteplase is non-­inferior to alteplase among patients with AIS.We aimed to delineate the association of the stroke onset to treatment time(OTT)with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.Methods This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-­2 an open-­label,randomised,controlled,non-­inferior trial.A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned(1:1)to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg.The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days.A post hoc subgroup analysis was conducted with the OTT divided into three intervals(0–90 min,91–180 min and 181–270 min).The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-­thrombolytic treatment.Results Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase(n=707)or alteplase(n=705).The OR of primary efficacy outcome was similar as OTT increased(p=0.84).Adjusted odds of an excellent functional outcome were 0.99(95%CI 0.37 to 2.67)for 0–90 min,1.23(95%CI 0.88 to 1.71)for 91–180 min and 1.21(95%CI 0.88 to 1.65)for 181–270 min.All were in favour of the tenecteplase group.Meta-­analysis of 2949 patients yielded a pooled risk difference of 5.54(95%CI-0.18 to 11.26;p=0.82)in favour of tenecteplase for more than 180 min and 1.77(95%CI-2.66 to 6.20;p=0.58)for 0–180 min.Conclusions In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset,there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis

Background: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. Methods: WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (w = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline;w = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-10, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6g were investigated by immunohistochemistry (IHC). Results: Acanthosis (98.46±14.12 vs. 222.68土71.10μm, P<0.01) and dermal cell infiltration (572.25±47.45 vs. 762.47土 59.59cells/field, P< 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83±5112.09 vs. 4093.19±2591.88 pirn2, P< 0.01) and scales (100,935.24 ±41,167.77 vs. 41,604.41 ± 14,184.10 μm, P<0.01) as compared with WT mice. In skin lesions ot IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. Conclusions: IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.

Effectiveness of intravenous r- tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study

Background Intravenous recombinant tissue plasminogen activator(r-tPA)and urokinase(UK)are both recommended for the treatment of acute ischaemic stroke(AIS)in China,but with few comparative outcome data being available.We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China.Methods A pre-planned,prospective,nationwide,multicentre,real-world registry of consecutive patients with AIS(age≥18 years)who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017-2019.The primary effectiveness outcome was the proportion of patients with an excellent functional outcome(defined by modified Rankin scale scores 0 to 1)at 90 days.The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions.Multivariable logistic regression was used for comparative analysis,with adjustment according to propensity scores to ensure balance in baseline characteristics.Results Overall,4130 patients with AIS were registered but 320 had incomplete or missing data,leaving 3810 with available data for analysis of whom 2666 received r-tPA(median dose 0.88(IQR 0.78-0.90)mg/kg)and 1144 received UK(1.71(1.43-2.00)×104 international unit per kilogram).There were several significant intergroup differences in patient characteristics:r-tPA patients were more educated,had less history of stroke,lower systolic blood pressure,greater neurological impairment and shorter treatment times from symptom onset than UK patients.However,in adjusted analysis,the frequency of excellent outcome(OR 1.18,95%CI 1.00 to 1.40,p=0.052)and symptomatic intracranial haemorrhage(OR 0.70,95%CI 0.33 to 1.47,p=0.344)were similar between groups.Conclusions UK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China.Registration http://www.clinicaltrials.gov.unique identifier:NCT02854592.

Effect of Matrix Metallopeptidase 13 on the Function of Mouse Bone Marrow-derived Dendritic Cells

Background： Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 （MMP- 13）, a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells （DCs）. The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis. Methods： Bone marrow-derived dendritic cells were obtained fiom C57BL/6 mice. One short-interfering RNA specific for MMP- 13 was used to transfect DCs. MMP-13-silenced DCs and control DCs were prepared, and apoptosis was measured using real-time polymerase chain reaction and Western blotting. MMP-13-silenced DCs and control DCs were analyzed for surface expression of CD80 and CD86 and phagocytosis capability using flow cytometry. Results： Compared to the control DCs, MMP- 13-silenced DCs increased expression of anti-apoptosis-related genes, BAGl （control group vs. MMP-13-silenced group： 4.08 ± 0.60 vs. 6.11 ± 0.87, P = 0.008）, BCL-2 （control group vs. MMP-13-silenced group： 7.54 ± 0.76 vs. 9.54 ± 1.29, P = 0.036）, and TP73 （control group vs. MMP- 13-silenced group： 4.33 ± 0.29 vs. 5.60 ±0.32, P = 0.001 ） and decreased apoptosis-related genes, CASPI （control group vs. MMP- 13-silenced group： 3.79±0.67 vs. 2.54±0.39, P - 0.019）, LTBR （control group vs. MMP- 13-silenced group： 9.23 ±1.25 vs. 6.24 ± 1.15, P = 0.012）, and CASP4 （control group vs. MMP-13-silenced group： 2.07 ± 0.56 vs. 0.35 ±0.35, P = 0.002）. Protein levels confirmed the same expression pattern. MMP- 13-silenced groups decreased expression of CD86 on DCs; however, there was no statistical difference in CD80 surface expression. Furthermore, MMP-13-silenced groups exhibited weaker phagocytosis capability. Conclusion： These results indicate that MMP-13 inhibition dampens DC maturation, apoptosis, and phagocytosis.