Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

【Objective】 To explore the clinical value of thromboelas-tography, coagulation four items and platelet count in guiding platelet transfusion in critically ill patients. 【Methods】 A total of 188 critically ill patients in Intensive Care Unit of our hospital from January 2020 to January 2022 were selected as subjects, and were divided into study group(n=89) and the control(n=99) according to the presence of bleeding symptoms. T-test was used for comparative analysis between the two groups. Spearman was used to analyze the correlation between TEG, coagulation four items and platelet count, and binary Logistic regression analysis was used to predict the influential factors of bleeding in critically ill patients, ROC curve was used to analyze the guiding value of the above-mentioned indexes for platelet transfusion. 【Results】 1) K and PT values in the study group, above the normal range, were significantly higher than those in the control, while the Angle value, MA value, CI value, FIB value and platelet count were significantly lower than those of the control, among which MA value, CI value and platelet count were below the normal range. 2) TEG, coagulation four items and platelet count were correlated. MA and CI values were positively correlated with platelet count, instead, R and K values were negatively correlated. R value was positively correlated with PT and APTT, CI value, on the contrary, was negatively correlated, K value was positively correlated with PT, while Angle value and MA value were negatively correlated. 3) Binary Logistic regression analysis showed that decreased MA value and decreased platelet count were independent risk factors for predicting bleeding in critically ill patients(P<0.05). 4) ROC curve analysis showed that the areas under ROC curve corresponding to Angle value, MA value, CI value, FIB value and platelet count were 0.866, 0.932, 0.9, 0.838 and 0.987(P<0.05). The sensitivity was highest in platelet count and lowest in FIB. The specificity was highest in MA and lowest in Angle. Compared with the single index, the area under the curve of the combined index(K value, MA value, CI value, PT value and platelet count) was 0.995(P<0.05), Yoden index 0.944, sensitivity 100%, specificity 93.3%, all higher than the individual index. 【Conclusion】 Thromboelas-tography combined with coagulation four items and platelet count can be used to accurately predict the critically ill patients with bleeding risk. To guide clinical platelets transfusion, the combined use of indexes, including K value, MA, CI value, PT and platelet count, is superior to separate use of them as the former showed better sensitivity and specificity, demonstrating a good clinical value.

Objective:By comparing the clinical effect of minimally invasive hollow screw internal fixation Assisted by orthopedic robot (TiRobot) and O-arm navigation in the treatment of pelvic fractures, and practicability and security of both treatments were evaluated.Methods:Retrospective analysis of data of 42 cases of Tile C type pelvic fractures was employed during June 2017 to June 2020. Among them, 32 cases, twenty-four men, eight women, aged 34±6.2 years (range 24-68 years), were treated with percutaneous screw fixation guided by O-arm X wire instrument. According to Tile classification, there were 3 cases of C1.1 type, 8 cases of C1.2 type and 21case of C1.3 type. According to the Denis classification of sacral fractures, 17 cases were in zone I, and 8 cases in zone II. Ten patients, eight males and two females, aged 36±5.2 years (range 19-62 years) were treated by percutaneous screw fixation assisted by orthopedic robot. According to Tile classification, there were 1 case of C1.1 type, 2 cases of C1.2 type and 7 cases of C1.3 type. According to the Denis classification of sacral fractures, there were 5cases in zone I, 2 cases in zone II. For those who got obviously displaced pelvic fractures, Starr frames were used and then internal fixation was used to fix pelvic anterior ring and posterior ring injury respectively. Based on the times of needle adjustments, intraoperative fluoroscopy time, good screw position and incidence of complications two groups were statistically analysed. Matta score was employed to evaluate the quality of fracture reduction, while the Majeed score was employed to evaluate the clinical efficacy. Through the two groups of cases guide needle adjustment times, intraoperative fluoroscopy time, screw position excellent and good rate and the incidence of complications, which were statistically analyzed.Results:All screw positions were confirmed by CT scan after operation. The average time required for each screw placement of the O-arm group was 7.36±2.63 s, of the robot group was 6.80±3.20 s, so difference was not statistically significant ( P<0.05). An average of screw adjustments per one screw was 1.56±0.02 times by O-arm, and by the robot group was 0.34±0.06 times, so differences between the two groups were statistically significant ( P>0.05). The average operating time of O-arm group was 53.86±15.06 min, while the robot group was 52.52±15.14 min, so differences between the two groups were not statistically significant ( P>0.05). Position distribution of screw placement in two groups, all screws in O-arm group of position evaluations were excellent, excellent rate was 100%, all screw position evaluations by robot were excellent, excellent rate was 100%, so difference in screw distribution between the two groups was not statistically significant ( P>0.05). All cases were followed up for 6-12 months. Fracture healing time: 34.6±8.6 weeks for O-arm group, 33.4±9.4 weeks for robot group. Comparison between the two groups was not statistically significant ( P>0.05). Majeed score of O-arm group was 55-87, including Excellence of 17 cases, goodness of 9, fairness of 6. The rate of excellence and goodness was 81.2%, while robot group was 76-95, and that were excellent 7 cases,1 good, and the excellent and good rate was 80%, there was no significant difference between Matta and Majeed score between the two groups ( P>0.05). The incidence of complications between the two groups were no statistically significant ( P>0.05). Conclusion:Orthopedic robot system and O-arm navigation system assisted by percutaneous hollow screw fixation treatment of pelvic anterior and posterior ring injury, which are accurate, safe, minimally invasive, can reduce radiation damage to patients and surgeons. The efficacy were satisfactory. Both treatments are ideal for minimally invasive treatment of pelvic fractures, and the orthopedic robot have advantages of being programmed, standardized, stable and it’s learning curve is shorter.

Objective:To investigate the feasibility and clinical efficacy of percutaneous screw fixation for acetabular anterior column fracture with laser-assisted axial fluoroscopy.Methods:Data of 20 patients (22 sided) with acetabular anterior column fracture treated by percutaneous screw fixation with laser-assisted axial fluoroscopy from January 2017 to December 2018 were retrospectively analyzed. There were 11 males and 9 females with an average of 42.1±3.2 years (range, 24-68 years). There were 7 cases of unilateral acetabular anterior column fracture, 2 cases of bilateral acetabular anterior column fracture (4 sides), 7 cases of anterior column with ipsilateral sacral fracture, and 4 cases of anterior column with sacroiliac joint injury. There were 3 hips of Area I, 6 Area II, 13 Area III of acetabular anterior column fractures according to Nakatani partition. The time from injury to surgery was 5 days (range, 3-11 days). All patients with acetabular anterior column fractures were fixed by percutaneous screw fixation with laser-assisted axial fluoroscopy, and patients with sacral fracture or sacroiliac joint injury were fixed by percutaneous sacroiliac screws with Starr frame-assisted reduction. The time of operation, the number of intraoperative fluoroscopy and the amount of intraoperative bleeding were recorded. Matta scoring criteria were used to assess fracture reduction quality, and hip function was assessed at the last follow-up according to the modified Merle D' Aubigné and Postel scoring system.Results:The average operative time was 22±10 min (range, 20-40 min) with an average times of intraoperative fluoroscopy of 30±8 times (range, 21-45 times), and the amount of intraoperative blood loss was 20±5 ml (range, 10-40 ml). 20 patients were followed up after operation for a period of 14±3.1 months (range, 12-18 months). The quality of postoperative fracture reduction was assessed according to the Matta acetabular fracture reduction criteria: anatomical reduction in 18 hips, satisfactory reduction in 2 hips, unsatisfactory reduction in 2 hips, with an excellent and good rate of 91% (20/22). The fracture healing time was 13±2.2 weeks (range, 11-16 weeks). At the lastest follow-up, hip function was assessed according to the modified Merle D' Aubigné and Postel scoring system: excellent 18, good 3, fair 1, and the satisfactory rate was 95%(21/22). No major neurological, vascular injury, wound infection and ectopic ossification were found during follow-up.Conclusion:Using laser-assisted axial fluoroscopy percutaneous screw to treat acetabular anterior column fracture, the operation is simple. And there is low risk to damage important blood vessels and nerves. This method can shorten the operation time of acetabular anterior column fracture, reduce the amount of blood loss during the operation, and the outcome is satisfactory.

Data of patients with maxillofacial and jugular venous malformations involving isthmus faucium area from January 2012 to July 2016 were collected. Patients were questioned about the medical history before operation, and the airway was adequately evaluated. The patients diagnosed as having non-difficult airways were endotracheally tubed using fast induction of anesthesia. Tracheal intubation was per-formed using fast induction of anesthesia combined with topical anesthesia after visual laryngoscopy in the patients assessed as having difficult airways. Endotracheal intubation was guided with a visual hard endo-scope or a fibrobronchoscope in the patients with difficulty in opening mouth after multiple treatments. Post-operative airway management was as follows: the tracheal tube was removed after extubation, the tracheal tube was retained for 24-48 h, or preventive tracheotomy was performed. Oxygen was inhaled by mask. A total of 157 patients were included in this study, 55 patients diagnosed as having difficult airways, and a-mong the 55 patients, 87％ cases were intubated after visual laryngoscopy and 13％ cases received tracheot-omy. There were 10 patients with difficulty in opening mouth after multiple treatments and 5 cases under-went tracheotomy in the outer hospital. Sixteen patients presented with a transient increase in airway pres-sure during intraoperative injection of anhydrous ethanol. There were 106 cases in whom the tracheal tube was removed immediately after emergence, and among them, 32. 1％ cases needed tongue traction and 2. 8％ cases underwent emergency tracheotomy after extubation. Thirty-eight patients needed to retain the tracheal tube for 24-48 h after operation, and among them, 37％ cases needed tongue traction and 3％ ca-ses required emergency tracheotomy after extubation. Thirteen cases underwent preventive tracheotomy. The preoperative visit and assessment are especially important, appropriate airway management strategies should be developed, vital signs should be closely observed during operation, and the timing of extubation should be grasped for this type of patients, and the SpO2 and airway pressure should be mainly observed during op-eration especially for the patients who underwent anhydrous ethanol injection.

Objective: To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF) including diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry (EnVision method) and molecular detection of glioma-associated oncogene homologue 1 (GLI1) gene translocation were performed. All cases were histologically reviewed with immunohistochemical staining for smooth muscle actin (SMA), CD10, CD117, DOG1, CD34, ER, PR, ALK and S-100. Fluorescence in situ hybridization (FISH) was used to detect the GLI1 gene translocation, and mutation of CKIT exons 9, 11, 13 and 17; and PDGFRA exons 12, 14 and 18 were identified by Sanger sequencing in four cases. Relevant literature was reviewed. Results: The study included four men and four women, age ranged from 26 to 72 years (mean 51 years). Histologically, the tumors were rich in small thin-walled blood vessels and myxoid matrix, and exhibited multiple nodular growth pattern in the gastric wall. The tumor cells were bland, spindled or oval. Immunohistochemically, all cases strongly expressed vimentin and SMA, and some expressed CD10 (4/8), desmin (3/8), H-caldesmon (5/8) and PR (5/8), but were negative for CD34, S-100, ER, ALK, CD117 and DOG1. The GLI1 gene translocation detection was performed in eight cases by FISH with three positive cases and five negative cases. Mutation analyses for exons 9, 11, 13, and 17 of CKIT genes and exons 12, 14, and 18 of the PDGFRA genes were performed and the tumors all of four tested cases were wild-type. Seven patients were followed up (ranged from 24 to 95 months, mean 50 months) after diagnosis and none of the patients had recurrence or metastasis. Conclusions PF is a rare novel mesenchymal tumor of the stomach. Its distinct clinicopathologic features and immunohistochemical positivity for SMA, CD10 and PR can help differentiating this entity from other gastrointestinal mesenchymal tumors. FISH detection of GLI1 gene translocation offers an additional molecular diagnostic marker for the diagnosis.

Objective To investigate the association of distinct myositis specific autoantibodies (MSAs) with long-term survival of patients with polymyositis (PM) and dermatomyositis (DM).Methods We analyzed the clinical data and outcome of patients with PM and DM who were hospita-lized in the department of rheumatology of China-Japan Friendship hospital from 1994 to 2015,and evaluated the impact of MSAs on the prognosis of patients.Multivariate Cox regression analysis was used to identify the prognostic risk factors for PM/DM patients.Results A total of 383 PM/DM patients were followed up for 1-333 months.Cumulative survival and 10-year survival rate of all patients were 68.6％ and 76.2％,respectively.The survival rate of 80.4％ and 77.1％ at 3 and 5 years in patients with MSAs,which were lower than those of patients with-out MSAs,who had the survival rate of 90.1％ and 87.4％ at 3 and 5 years,respectively(x2=3.90 and 3.98,P＜0.05).There was significant difference for long-term survival in all MSAs positive groups (x2=40.654,P=0.000).Anti-MDA5 positive patients who had the 10-year survival rate of 28.7％ had the worst prognosis,while anti-HMGCR positive patients who had the l0-year survival rate of 100％ had the best outcome in all groups.Multivariate Cox regression analysis showed that independent risk factors associated with the long-term survival of patients were age of onset,complicated with malignancies,dysphagia,rapidly progress interstitial lung disease,antiMDA5 antibody positive,increased serum aspartate transferase and C reaction protein.Conclusion MSAs are strongly associated with the prognosis of patients with PM/DM.Patients with MSAs has worse 5-year overall survival than those without MSAs,which indicates that screening MSAs and aggressive treatment for PM/DM patients at very early stage of disease may improve the outcome.

Objective To analyse the clinicopathologic features of gastric plexiform fibromyxoma (PF)including diagnosis,differential diagnosis,immunohistochemistry and molecular pathology. Methods Eight cases of PF were collected from June 2006 to June 2017 at the Second Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University. The clinicopathologic findings of eight cases of PF were retrospectively analyzed, and immunohistochemistry(EnVision method)and molecular detection of glioma?associated oncogene homologue 1(GLI1)gene translocation were performed. All cases were histologically reviewed with immunohistochemical staining for smooth muscle actin(SMA), CD10, CD117,DOG1,CD34,ER,PR,ALK and S?100. Fluorescence in situ hybridization(FISH)was used to detect the GLI1 gene translocation,and mutation of CKIT exons 9,11,13 and 17;and PDGFRA exons 12, 14 and 18 were identified by Sanger sequencing in four cases. Relevant literature was reviewed. Results The study included four men and four women, age ranged from 26 to 72 years(mean 51 years). Histologically,the tumors were rich in small thin?walled blood vessels and myxoid matrix,and exhibited multiple nodular growth pattern in the gastric wall. The tumor cells were bland, spindled or oval. Immunohistochemically,all cases strongly expressed vimentin and SMA,and some expressed CD10(4/8), desmin(3/8), H?caldesmon(5/8)and PR(5/8), but were negative for CD34, S?100, ER, ALK, CD117 and DOG1. The GLI1 gene translocation detection was performed in eight cases by FISH with three positive cases and five negative cases. Mutation analyses for exons 9, 11, 13, and 17 of CKIT genes and exons 12,14,and 18 of the PDGFRA genes were performed and the tumors all of four tested cases were wild?type. Seven patients were followed up(ranged from 24 to 95 months,mean 50 months)after diagnosis and none of the patients had recurrence or metastasis. Conclusions PF is a rare novel mesenchymal tumor of the stomach. Its distinct clinicopathologic features and immunohistochemical positivity for SMA, CD10 and PR can help differentiating this entity from other gastrointestinal mesenchymal tumors. FISH detection of GLI1 gene translocation offers an additional molecular diagnostic marker for the diagnosis.

Objective To investigate the clinical efficacy of recombinant human epidermal growth factor in the treatment of recurrent oral ulcers in elderly patients.Methods 82 cases of elderly patients in our hospital in the treatment of recurrent oral ulcer were selected,41 cases in the control group,the conventional western medicine treatment,41 cases of the study group,recombinant human epidermal growth factor in treatment before and after treatment,blood determination of immune status,clinical efficacy and adverse reactions of comparison were performed at one-year follow-up.Results the effective rate of treatment group is lower than 78.05％of the effective rate of treatment group 95.12％,study group 3,6 and 12 months recurrence rate(4.88％,7.32％,7.32％)than in the control group the recurrence rate(19.51％,24.39％,29.27％),the study group after the treatment of CD3+ and CD4+/CD8+ and NK were higher than the control group,the CD8+ level is lower than the control group(P<0.05),the two groups had no serious adverse reaction.Conclusion recombinant human epidermal growth factor is effective in the treatment of oral ulcer.

Objective:To evaluate the effect of Nutlin-3,a MDM2 antagonist,on the pyroptosis in SMMC-7721 cells.Methods: The expression of actived caspase-1(p20) and IL-1β was detected using Western blot analysis.Pyroptosis was investigated by a standard lactate dehydrogenase release assay(LDH).IL-1β content in the cell culture supernatant was quantified by ELISA.Results: Nutlin-3 up-regulated the expression level of actived caspase-1 and IL-1β in SMMC-7721 cells.Meanwhile,Nutlin-3 increased significantly the content of LDH and IL-1β in the cell culture supernatant(P<0.05).Conclusion: Nutlin-3 activated pro-caspase-1,promoted pyroptosis and IL-1β release in SMMC-7721 cells.