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 investigate the feasibility and clinical efficacy of using the mirror technique, which involves overlapping the distance between the center of rotation of the femoral head and the posteromedial edge of the greater trochanter, combined with the injured side and the posterior edge of the contralateral femoral medial and lateral condyles, to correct rotational displacement of the femur during closed reduction and intramedullary nail fixation for multi-level comminuted femoral shaft fractures.Methods:This study included 52 adult patients with unilateral comminuted femoral shaft fractures treated with closed reduction and antegrade interlocking intramedullary nail fixation at the Trauma Center of Liuzhou Workers' Hospital from January 2020 to December 2022. The cohort consisted of 37 males and 15 females, with an average age of 44.4±3.5 years (range 19-68 years). During the operation, C-arm fluoroscopy was used to confirm the standard lateral position of the knee joint, identified by overlapping the posterior edges of the medial and lateral femoral condyles. With this position maintained, X-ray fluoroscopy was performed on the hip joint in the anteroposterior view to identify the rotation center of the femoral head (point O) and the intersection point of the arc projection between the posteromedial edge of the greater trochanter and the upper edge of the femoral neck (point Y). The distance from point O to point Y (OY) was measured and recorded. The rotational deformity of the femoral shaft fracture was corrected by internally or externally rotating the main screw sight frame to match the OY distance between the injured and healthy sides. Postoperative CT was used to measure bilateral femoral neck anteversion (FNA), and the difference in FNA between the two sides was compared to verify the accuracy of rotation control. Clinical efficacy was evaluated based on fracture healing rate, lower extremity functional scale (LEFS) score, Harris score, Lysholm knee score, hip and knee joint range of motion, and complications.Results:The postoperative FNA was 14.45°±3.23° on the healthy side and 14.21°±3.28° on the injured side. The mean FNA difference between the two sides was 0.79°±0.58° (range 0°-2.5°). In 3 cases, the difference exceeded 2°, with a maximum difference of 2.5°. In 10 cases, the difference ranged from 1° to 2°, and in 39 cases, the difference was ≤1°, including 2 cases with no difference. There was no significant difference in postoperative FNA between the two sides ( t=1.063, P=0.168). At the last follow-up, there were no significant differences in LEFS score, Harris score, or Lysholm score between the injured and healthy sides ( P>0.05). The range of motion (ROM) of the hip joint at the last follow-up was 117.0°±2.2° in flexion, 24.3°±3.2° in extension, 33.4°±3.1° in abduction, 20.8°±2.7° in adduction, 19.4°±3.5° in internal rotation, and 38.2°±1.5° in external rotation. The ROM of the healthy side was 122.0°±2.4° in flexion, 25.4°±2.8° in extension, 35.6°±2.0° in abduction, 23.4°±1.6° in adduction, 21.0°±2.2° in internal rotation, and 38.4°±1.8° in external rotation, with no significant differences ( P>0.05). The knee flexion ROM was 135.0°±2.8° on the injured side and 138.4°±1.2° on the healthy side, with no significant difference ( P>0.05). The fracture healing time was 10.6±2.3 months (range 6-13 months). One patient developed fat embolism syndrome on the third postoperative day and recovered after 2 weeks of hormone therapy and respiratory support. No other complications, such as vascular or nerve injury, infection, deep vein thrombosis, or joint dysfunction, were observed in the remaining 51 patients. Conclusion:The method of using the vertical projection distance between the center of rotation of the femoral head and the posteromedial edge of the greater trochanter, combined with the overlap of the injured side and the posterior edge of the medial and lateral femoral condyles, is a new quantitative approach. This technique accurately determines and corrects the rotational displacement of femoral fractures, offering an effective and quick intraoperative correction method.

Objective:To investigate the early clinical effects of orthopedic surgery robot-assisted double Endobutton titanium plate internal fixation in the treatment of fresh acromioclavicular joint dislocation.Methods:Thirty-nine patients with fresh acromioclavicular joint dislocation were included from January 2020 to January 2022. A total of 19 patients were treated with double Endobutton suspension internal fixation assisted by the domestic third-generation orthopaedic surgical robot (TiRobot ? 2.0) Dimensity system. There were Rockwood type III in 11 cases, type IV in 8 cases. Twenty cases were treated with conventional incision double Endobutton internal fixation, with Rockwood type III in 13 cases, type V in 7 cases. The operation duration, blood loss volume, incision length and hospitalization time were compared between the two groups. The following CT parameters of acromioclavicular joint at 2 days and 1 year after operation, distance between distal inferior cortex of clavicle and subacromial cortex, distance between upper and lower endobuttons, horizontal distance between anterior edge of distal clavicle and anterior edge of acromion and diameter of coracoid process and diameter of clavicular tunnel were measured. The visual analogue score (VAS), Constant-Murley shoulder function score and shoulder abduction activity were also evaluated before and at 12 months after operation. Results:The follow-up duration was 10.8±2.4 months in the robot group and 11.5±3.1 months in the routine group. The VAS score of the robot group decreased from 5.3±2.1 to 0.3±0.2 at 12 months after operation ( t=10.46, P=0.014). The Constant-Murley score increased from 55.6±6.4 to 92.0±4.2. The range of shoulder abduction increased from 42.2°±5.4° to 172.6°±6.1° ( t=17.24, P<0.001). The operation duation of the robot group was 74.4±6.6 min, which was longer than that of the conventional group 61.7±7.2 min ( t=5.43, P=0.037). There was no significant difference in VAS score, Constant-Murley score, shoulder abduction activity or CT measurement between the two groups ( P>0.05). During the follow-up, two cases in the robot group had cortical osteolysis on the supraclavicular surface, one case in the conventional group had loss of reduction, one case in the supraclavicular cortical osteolysis, and 4 cases in the cortical defect on the side of the coracoid process tunnel. Conclusion:Orthopedic robot-assisted and conventional incision with double Endobutton titanium plate internal fixation in treating fresh acromioclavicular joint dislocation can achieve satisfied early clinical effects. Accurate establishment of clavicle and coracoid bone tunnel assisted by robot can overcome the defects of bone tunnel deviation in conventional incision operation and can prevent reduction and bone loss. However, robot-assisted and conventional incision Endobutton internal fixation could enlarge bone tunnel.

Objective:To investigate the distribution of pathogen species isolated from cerebrospinal fluid culture (CSF) in children and analyze the antibiotic-resistance of the main isolates in vitro, which provides reference for interpreting the pathogens and choosing antibiotics in empiric therapy for pediatric patients. Methods:The results of cerebrospinal fluid culture were collected by checking laboratory information system of the Children′s Hospital of Zhejiang University and the clinical characteristics of these children were analyzed retrospectively by checking electronic medical record system.Results:A total of 1 312 isolates were detected, including 1 294 isolates of bacteria and 18 isolates of fungi. A total of 497 (37.9%) isolates were pathogenic microorganisms, of which 288 (57.9%) isolates were gram-positive, 200 (40.3%) isolates were gram-negative, and 9 (1.8%) isolates were fungi. The top 5 pathogens were Escherichia coli (102 isolates, 20.5%), Streptococcus pneumoniae (64 isolates, 12.9%), Streptococcus agalactiae (52 isolates, 10.5%), Enterococcus faecium (33 isolates, 6.6%) and Staphylococcus aureus (28 isolates, 5.6%). Most of the Streptococcus pneumoniae strains were isolated from children more than 1 year old (76.6%, 49/64), while the other top 4 bacteria were mainly isolated from infants less than 1 year old, with the rate of 95.1%(97/102) for Escherichia coli, 98.1%(51/52) for Streptococcus agalactiae, 81.8%(27/33) for Enterococcus faecium and 71.4% (20/28) for Staphylococcus aureus. A total of 815 (62.1%) isolates were considered to be contaminated pathogens according to the analysis on clinical manifestations and other laboratory findings in CSF, and coagulase-negative Staphylococcus (680 isolates), Micrococcus (50 isolates), Corynebacterium (28 isolates) and Enterococcus faecium (23 isolates), which accounted for 41.1% (23/56) of the total detected Enterococcus faecium, were the top 4 contaminated bacteria. During the study period, the isolation rate of the pathogenic microorganisms increased year by year (χ2=34.84, P<0.001), while the isolation rate of the contaminated pathogens, which detected mainly in summer and autumn, decreased year by year (χ2=13.26, P<0.001). Conclusions:The predominant bacteria causing pediatric purulent meningitis were Escherichia coli, Streptococcus pneumoniae, Streptococcus agalactiae, Enterococcus faecium and Staphylococcus aureus. Coagulase-negative Staphylococcus, Micrococcus, Corynebacterium and Enterococcus faecium were common contaminated bacteria in CSF culture, therefore clinicians should interpret the results of CSF culture cautiously according to the bacterial species and clinical manifestations.

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.

Objective To explore the drug sensibility of Brucella from bovine and sheep in Xinjiang.Methods Using paper diffusion method,19 drugs of 8 kinds of antibiotics including aminoglycosides,macrolides,sulfonamides,tetracyclines,β-lactams,fluoroquinolones,chloramphenicols and rifamycins,were tested.Drug sensitivity test was conducted on 57 Brucella strains isolated from bovine and sheep in Xinjiang from 2010 to 2016.Results The 57 Brucella strains were highly sensitive to doxycycline,tetracycline,streptomycin,tobramycin,gentamicin,amikacin,amoxicillin,ofloxacin,fleroxacin,ciprofloxacin and chloramphenicol,with the sensitivity rates were all higher than 90％;and they were highly resistance to azithromycin,clarithromycin and bactrim,with the drug resistance rates were all higher than 80％.Conclusion Brucella from bovine and sheep in Xinjiang is sensitive to tetracyclines,aminoglycosides,β-1actams,fluoroquinolones and chloramphenicols.

The distribution of authors, institutions that published papers, and key words in CNKI-covered papers on library information service model was analyzed, which showed that there are a number of high production authors in China engaged in studies on library information service model but the number of cooperative studies is few, aca-demic libraries are active in performing related studies but public libraries seldom participate in such studies, the related studies are focused on the application of information technologies and the personal demands of users.

Objective:The characteristics of lymph node metastasis were investigated to guide the range of lymph node dissection during the radical operation of distal gastric cancer. Methods:The clinical data of 773 patients with distal gastric cancer who under-went radical distal subtotal gastrectomy at the Tianjin Medical University Cancer Institute and Hospital between February 2010 and September 2014 were reviewed and analyzed to infer the potential clinical mechanisms of lymph node metastasis. Results:Among the included patients, 423 (54.72%) had lymph node metastasis. The proportion of metastasis in the patients from the highest to the lowest rate was observed in group NO. 6, 3, 4sb, and 5 lymph nodes. The metastasis rates of the N1 lymph nodes from the highest to the low-est were observed in group NO. 3, 6, 5, and 4d lymph nodes, whereas those of the N2 lymph nodes occurred in group NO. 8a, 7, and 1 lymph nodes. Group NO. 8a lymph node with skipped metastasis was observed in 50.68%of the patients. Conclusion:During radical distal gastric cancer surgery, attention should be given to the possibility of metastasis in group NO. 8a lymph node. Appropriate exten-sion of the lymph node dissection should be conducted when necessary.

OBJECTIVETo explore the association of perioperative blood transfusion (PBT) with survival of gastric cancer after surgery.

METHODSWe retrospectively reviewed the medical records of 1 000 gastric cancer patients, including 738 non-transfused (73.8%) and 262 transfused (26.2%) cases. A one to one match was created using propensity score analysis, except preoperative hemoglobin level and operative blood loss. The survival was analyzed by Kaplan-Meier survival model.

RESULTSThe 5-year survival rate of the 1 000 cases of gastric cancer patients was 39.9%. Before matching, there was a significant difference between transfused group (33.6%) and non-transfused group (49.1%, P<0.005). Univariate analysis showed that age, tumor size, hemoglobin level, albumin level, depth of invasion, lymph node metastasis, lymph node dissection, surgery mode, adjuvant chemotherapy, blood loss and blood transfusion during perioperative period were associated with prognosis in the gastric cancer patients (all P<0.05). Multivariate analysis showed that tumor invasion, lymph node metastasis, lymph node dissection, chemotherapy and perioperative blood transfusion were independent prognostic factors in gastric cancer (all P<0.05). After matching, the 5-year survival rate of the 262 non-transfused patients was 37.7%, while that of the 262 transfused patients was 33.6% (P>0.05).

CONCLUSIONSPerioperative blood transfusion has no significant effect on the prognosis of gastric cancer patients.

Analysis of Variance ; Blood Transfusion ; mortality ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision ; Lymphatic Metastasis ; Perioperative Period ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; mortality ; pathology ; surgery ; Survival Rate

OBJECTIVE: To construct an eukaryotic expression vectors containing superantigen staphylococcal enterotoxin A (SEA) gene, and to identify its expression in laryngeal squamous carcinoma cells. METHOD: SEA full-length gene fragment was obtained from ATCC13565 genome of the staphylococcus, referencing standard strains producing SEA. Coding sequence of SEA was artificially synthetized. Than, SEA gene fragments was subcloned into eukaryotic expression vector pIRES-EGFP. The recombinant plasmid pSEA-IRES-EGFP was constructed and was transfected to laryngocarcinoma Hep-2 cells. Resistant clones were screened by G418. The expression of SEA in laryngocarcinoma cells was identified with ELISA and RT-PCR method. RESULT: The subclone of artificially synthetized SEA gene was subclone to eukaryotic expression vector pires-EGFP. Flanking sequence confirmed that SEA sequence was fully identical to the coding sequence of standard staphylococcus strains ATCC13565 in Genbank. After recombinant plasmid transfected to laryngocarcinoma cells, the resistant clones was obtained after screening for two weeks. The clones were selected. The specific gene fragment was obtained by RT-PCR amplification. ELISA assay confirmed that the content of SEA protein in supernatant fluid of cell culture had reached about Pg level. CONCLUSION The recombinant eukaryotic expression vector containing superantigen SEA gene is successfully constructed, and is capable of effective expression and continued secretion of SEA protein in laryngochrcinoma Hep-2 cells after recombinant plasmid transfected to laryngocarcinoma cells.
Cell Line, Tumor ; Enterotoxins ; genetics ; Gene Expression ; Genetic Vectors ; Humans ; Plasmids ; Superantigens ; genetics ; Transfection