Atherosclerosis ; complications ; pathology ; Blood Platelets ; physiology ; Humans ; Platelet Activation ; Thrombosis ; etiology ; pathology

Eukaryotes inhibit the translation of mRNA under stress conditions and form particles-stress granules (stress granules). At present, stress granules have been proved to be related to the occurrence and development of a variety of diseases, including tumors. The production of stress granules is promoted by microenvironment such as hypoxia and hyperactive oxygen in tumor cells, while stress granules-related proteins such as G3BP1, RACK1, YB-1 and mammalian target of rapamycin (mTOR) can promote the occurrence and metastasis of tumors, but the mechanism is not yet clear. In addition, studies have linked the formation of stress granules to the survival of tumor cells during chemotherapy, and believe that stress granules play a role in the treatment of tumors by different anti-tumor drugs. This review introduces the biological characteristics of stress granules and their relationship with tumors.

Objective:To evaluate the significance of cerebrospinal fluid soluble triggering receptor expressed on myeloid cells 1 (strem-1) in early clinical diagnosis of post-neurosurgical bacterial meningitis (PNBM).Methods:Twenty-seven patients with PNBM (5 had etiology diagnosis and 22 had clinical diagnosis), accepted surgery in our hospital from October 2017 to October 2019, were chosen in our study; 40 patients with post-neurosurgical aseptic meningitis (PNAM) accepted surgery at the same period were selected as controls. Levels of strem-1 in the cerebrospinal fluid of patients from PNBM and PNAM groups were detected by enzyme linked immunosorbent assay (ELISA). The clinical data of these patients were compared; the differences of cerebrospinal fluid markers and strem-1 levels were compared between the two groups. Receiver operating characteristic (ROC) curve was used to evaluate the diagnosis significance of CSF markers and strem-1 in PNBM.Results:Patients with etiology diagnosed PNBM had significantly higher count of white blood cells (WBCs), levels of protein, lactic acid and strem-1 in the cerebrospinal fluid, and statistically lower glucose level than PNAM patients ( P<0.05). Patients with clinically diagnosed PNBM had significantly higher levels of protein, lactic acid and strem-1 in the cerebrospinal fluid than PNAM patients ( P<0.05). The area under the ROC curve of WBCs count, levels of protein, glucose, lactic acid and strem-1 in the cerebrospinal fluid for predicting clinically diagnosed PNBM were 0.703, 0.661, 0.644, 0.810 and 0.894, respectively; the cut-off value of strem-1 level in predicting clinically diagnosed PNBM was 42.5 ng/L, with specificity of 85% and sensitivity of 81.8%. Conclusion:The level of strem-1 in cerebrospinal fluid has certain value in early clinical diagnosis of neurosurgical PNBM.

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Objective:To investigate the clinical efficacy of wrist arthroscopic transosseous footprint repair technique for treating triangular fibrocartilage complex (TFCC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 56 patients with TFCC injury admitted to Shenzhen Second People′s Hospital from July 2017 to September 2020, including 38 males and 18 females, aged 17-45 years [(33.5±3.6)years]. All patients had unilateral injury. Physical examination showed instability of the distal radioulnar joint, and MRI and arthroscopy confirmed deep ligament injury of TFCC. All patients underwent repair of deep insertion of the TFCC by using wrist arthroscopic transosseous footprint. The operation time, intraoperative blood loss, wound healing and postoperative complications were recorded. The flexion and extension range of motion of the wrist, radial and ulnal deviation of the wrist, rotation range of motion of the forearm, patient related wrist evaluation (PRWE) score, modified Mayo wrist score, visual analogue scale (VAS), and percentage of grip strength between the affected side and unaffected side were compared preoperatively, at 3 months postoperatively and at 1 year postoperatively.Results:All patients were followed up for 12-18 months [(13.4±5.2)months]. The operation time was (61.3±8.9)minutes, with the intraoperative blood loss of (2.4±1.2)ml. All wounds were healed by first intension. There was no wound infection or ulnar nerve irritation symptom after operation. Four patients experienced clicking on the ulnar side of the wrist in a short period of time post-operation, with spontaneous disappearance of the symptom. At 3 months postoperatively, the radial and ulnar deviation of the wrist was decreased from (52.5±5.9)° preoperatively to (42.6±5.9)°, and rotation range of motion of the forearm was decreased from (94.9±8.4)°preoperatively to (84.6±5.9)° (all P<0.01). The flexion and extension range of motion of the wrist was (93.1±17.4)° preoperatively, with insignificant difference compared with (89.4±5.8)° at 3 months postoperatively ( P>0.05). At 1 year postoperatively, the flexion and extension range of motion of the wrist, radial and ulnar deviation range of motion of the wrist, and rotation range of motion of the forearm were significantly increased to (101.3±13.6)°, (52.4±6.6)°, and (116.4±16.4)° when compared with those at 3 months postoperatively (all P<0.01). At 3 months postoperatively, the PRWE score was increased to (17.1±3.8)points from (10.6±3.2)points preoperatively ( P<0.01), modified Mayo wrist score was decreased to (70.3±6.7) points from (78.1±12.7)points preoperatively ( P<0.01), VAS was decreased to (4.4±1.7)points from (6.2±1.5)points preoperatively ( P>0.05), and percentage of grip strength between the affected side and unaffected side was decreased to (55.7±8.7)% from (74.4±15.2)% preoperatively ( P<0.01). At 1 year postoperatively, the PRWE score was increased to (2.0±0.9)points, modified Mayo wrist score was increased to (94.8±3.3)points, VAS was decreased to (2.1±1.1)points, and percentage of grip strength between the affected side and unaffected side was increased to (93.2±8.7)% when compared with those at 3 months postoperatively (all P<0.01). Conclusion:Wrist arthroscopic transosseous footprint repair technique can effectively treat deep ligament injury of TFCC, with advantages of significantly improving postoperative joint range of motion and functional score, relieving the pain on the ulnar side of the wrist and enhancing grip strength.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective:To explore the relation of the radiochemical purity and in vivo imaging effect of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-phe1-Tyr3-Thr8-octreotide (TATE) injection. Methods:High performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) methods were established to determine 68Ga-DOTATATE, 68Ga 3+ , 68Ga in colloidal form and 68Ga-DOTA- D-Phe1-Tyr3-Thr8-dethreonine-octreotide (heptapeptide) and to study the influence of precursor purity on radiochemical purity of labelled products. The uptake of 68Ga-DOTATATE injection with different radiochemical purities was investigated in nude mice bearing AR42J cells by microPET imaging and the tumor target/non-target (T/NT) value was calculated. One-way analysis of variance and Pearson correlation analysis were used to analyze the data. Results:The contents of 68Ga 3+ and 68Ga in colloidal form were not related with precursor purity ( r values: 0.385, 0.497, P values: 0.306, 0.137), while the content of 68Ga-DOTA-heptapeptide was positively related with the purity of DOTA-heptapeptide ( r=0.957, P<0.001). The radiochemical purities of 68Ga-DOTATATE injection were (87.0±2.3)%, (86.8±0.8)% and (94.0±3.1)% when the DOTATATE purities were 90.9%, 91.6% and 99.2%, respectively. The results of microPET imaging showed that the tumor uptake was positively related with the radiochemical purity of 68Ga-DOTATATE injection ( r=0.828, P<0.001), and the T/NT values of 68Ga-DOTATATE injection with radiochemical purities of 95.7%, 85.8%, 84.5% and 79.9% were 21.25±8.84, 8.50±1.51, 11.38±1.65 and 6.01±0.99, respectively ( F=11.48, P=0.001). Conclusion:The radiochemical purity of 68Ga-DOTATATE injection is impacted by the purity of labelled precursor and manufacturing processes and is related with the imaging effect in vivo.

Objective: To observe and evaluate the clinical efficacy of laparoscopic abdominoperineal intersphincteric resection com-bined with ileostomy for the treatment of ultra-low rectal cancer. Methods: Clinicopathologic data of 74 patients undergoing laparo-scopic radical resection for ultra-low rectal cancer at Coloproctology Hospital of Chengdu from January 2015 to June 2017 were retro-spectively analyzed. In total, 43 patients underwent laparoscopic abdominoperineal intersphincteric resection combined with ileosto-my (ISR group), and 31 patients underwent laparoscopic low anterior resection combined with ileostomy (LAR group). The periopera-tive condition, radical resection of tumor, and postoperative anal function were compared between the two groups. Results: There were no significant differences in blood loss, postoperative hospital stay, and postoperative complications between the groups (all P>0.05). The mean operative time was (306.6 ± 25.1) minutes in the ISR group and (239.7 ± 26.4) minutes in the LAR group (P=0.010). There were no significant differences in pT and pN between the groups (all P values>0.05). The coincidence rate of T stage diagnosis was 93.0% in the ISR group and 93.5% in the LAR group. The positive rate of circumferential resection margin in the two groups was 0. The mean distance of the distal margin was (2.3±0.1) cm in the ISR group and (1.4±0.3) cm in the LAR group (P<0.001). All patients were followed up for 12-42 (mean 23.4) months. The local recurrence rate was 0 in the ISR group and 12.9% (4/31) in the LAR group (P=0.027); no distant metastasis was observed in any of the groups. There was no significant difference in the results of the anorectal manometry test between the groups (P>0.05). The proportion of patients with good continence of anal function after closure of ileos- tomy was 83.7% in the ISR group and 87.1% in the LAR group (P>0.05). Conclusions: Laparoscopic abdominoperineal intersphincteric resection combined with ileostomy is safe and feasible for the treatment of ultra-low rectal cancer, and it leads to satisfactory anal function and a short-term curative effect.

[Abstract] Objective:To prepare the third generation CAR-T cells targeting EGFRvⅢ (EGFRvⅢCAR-T) and to detect its specific killing effect against EGFRvⅢ+ U87 cells in vitro and in vivo. Methods: Human CD3+ T cells were transfected with lentiviral EGFRv Ⅲ/3CAR, which was generated by calcium phosphate co-precipitation of three plasmids. The expression of EGFRvⅢ/3CAR in T cells was detected by Western blotting and flow cytometry. In vitro killing effect of EGFRvⅢ/3CAR-T cells on EGFRvⅢ+ U87 cells was detected by 51Cr release assay. The secretion of cytokine IFN-γ of EGFRvⅢ/3CAR-T cells was detected by ELISA. Nude mouse xenograft model was constructed to detect the in vivo cytotoxicity of EGFRvⅢ/3CAR-T cells on xenograft tumor. Results: The EGFRvⅢ/3CAR lentivirus was successfully packaged with an average titer of 5×106 TU/ml. Western blotting showed that a protein band of approximate 58 000 molecular weight was observed in EGFRvⅢ/3CAR-T cells but absent in untransfected T cells. Flow cytometry indicated the average transduction efficiency of EGFRvⅢ/3CAR was 52.3%. 51Cr release assay showed that the specific killing effect of EGFRvⅢ/ 3CAR-T cells was positively correlated with E/T ratio (E∶T=4∶1, 8∶1, 16∶1, 32∶1). ELISA showed that cytokine IFN-γ secretion was (1 836±148.2) pg/ml, which was significantly different from that of NTT and GFP+ T cells (P<0.01). The specific killing activity of EGFRvⅢ/3CAR-T cells and IFN-γ secretion were both dependent on the expression level of EGFRvⅢ in U87 cells. The tumor growth monitoring results showed that the tumor volume of EGFRvⅢ/3CAR-T cell group was significantly different from that of GFP+ T cell group and PBS group around 3 weeks after injection (P<0.01). Conclusion: EGFRvⅢ/3CAR-T cells demonstrated specific antitumor effectagainstEGFRvⅢ+U87cellsbothinvitro and in vivo, providing basis for immunotherapyofgliomainfuture clinical use.

Objective: To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion. Methods: From May 2013 to August 2017, a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed, with mean age of 35.80±2.41 years (18-65 years). The duration from injury to treatment was averaged 11.70±1.90 months (5-18 months). All of the cases sustained waist and proximal end fractures. X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites. However, there were no serious deformities and wrist arthritis. The patients suffered pain and weakness at the radial side of the wrist. The type of the fractures were Slade-Geissler's III-VI, including grade III 4 cases, grade IV 13 cases, grade V 7 cases and grade VI 1 case. The patients were treated with arthroscopic debridement of the sclerotic bone, autologous bone grafting, percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation, followed by functional rehabilitation training. Bone union was assessed by serial plain radiographs and CT scan regularly. The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain, range of motion (ROM) and the grip strength, which were measured before operation and at 18 months after operation. Results: All cases were followed up. Bone union was achieved in all of 25 nonunion. The average radiological union duration was 10.24±2.10 weeks (6-20 weeks). The average VAS score decreased from 6.75±1.10 preoperatively to 1.33±0.21. The mean ROM of wrist was improved to 168.48°±12.41° (92.90% of that of the normal side), compared to that of 135.24°±17.47° preoperatively (79.80% of that of the normal side). The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46% of that of normal side) preoperatively to 48.75±4.42 kg (90.65% of that of normal side). The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37. Conclusion Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for scaphoid nonunion, which could protect the blood supply of the fracture sites, decrease the surgical complications, promote bone healing and lead to a faster recovery.