Immunotherapy has become the cornerstone of current malignant tumor treatment.However,the response of different patients to immunotherapy is highly heterogeneous,and not all patients can benefit from it.There is an urgent need to find biomarkers that can effectively predict the efficacy of immunotherapy.C-C chemokine ligand 4(CCL4)is a cytokine,belonging to the inflammatory CCL subfamily.It is mainly secreted by immune cells and tumor cells and shows low or no expression in normal tissues but abnormally high expression in various malignant tumor tissues.After binding to CCL4 and its receptor C-C chemokine receptor type 5(CCR5),it can recruit and mediate immune cell migration,destroy the stabili-ty of the tumor microenvironment(TME),participate in carcinogenesis and promote the development of tumors.In the tumor immune microenvironment,CCL4 can mediate and recruit the directed migration of key immune cells such as monocytes,macrophages,natural killer(NK)cells,and T cells,which makes it a potentially important element affecting the efficacy of im-munotherapy and has specific value.This paper reviews the research progresses of CCL4's effects on immune escape in TME,in order to provide clues and references for basic research and clinical diagnosis and treatment.

Objective:To compare the efficacy of the horizontal plate plus raft screws above the acetabulum and fixation with screws only for acetabular fractures combined with dome impaction in the aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 20 aged patients with acetabular fractures combined with dome impaction, who were admitted to Tianjin hospital between May 2013 and January 2023, including 5 males and 15 females, aged 61-84 years [(72.2±7.3)years]. According to Letournel and Judet classification, 13 patients had anterior column fracture, 5 anterior column fracture combined with posterior transverse fracture and 2 two-column fracture. All the patients underwent open reduction and internal fixation through an anterior approach. Of them, 11 patients were treated with the fixation with the horizonal plate plus raft screws above the acetabulum (plate plus raft screw group) and 9 with the screws only (screw only group). The operative time, intraoperative blood loss, and intraoperative fluoroscopy times were compared between the two groups. The quality of fracture reduction was evaluated with the Matta′s radiographic criteria at 3 days after surgery and the function of the hip joint was assessed with Merle D′Aubigné and Postel scoring system at 3 months after surgery and at the last follow-up as well as the excellent and good rate at te last follow-up. The occurrence of postoperative complications was observed.Results:All the patients were followed up for 6-18 months [(13.1±3.1)months]. There were no significant differences in the operative time, intraoperative blood loss or intraoperative fluoroscopy times between the two groups ( P>0.05). According to the Matta′s radiographic criteria at 3 days after surgery, patients with anatomical reduction and satisfactory reduction accounted 6 and 5 in the plate plus raft screw group, compared to 5 and 4 respectively in the screw only group ( P>0.05). The values of Merle D′Aubigné and Postel score at 3 months after surgery and at the last follow-up were (14.0±2.4)points and (15.8±2.2)points in the plate plus raft screw group, which were higher than those in the screw only group [(11.0±2.6)points and (13.0±3.1)points] ( P<0.01). The values of Merle D′Aubigné and Postel score at the last follow-up of both groups were further enhanced from those at 3 months after surgery ( P<0.01). At the last follow-up, 3 patients were rated excellent, 6 good, 1 fair and 1 poor in the plate plus raft screw group, with an excellent and good rate of 81.8%, while in the screw only group, 3 were rated good, 2 fair and 4 poor, with an excellent and good rate of 33.3% ( P<0.05). One patient in the plate plus raft screw group and 5 in the screw only group had displacement of the dome impaction fragment combined with traumatic arthritis after surgery ( P<0.05). Conclusion:For acetabular fractures combined with dome impaction in the aged patients, the horizontal plate plus raft screw above the acetabulum can effectively improve the function restoration of the hip joint and reduce the occurrence of the displacement of the dome impaction fragment and traumatic arthritis after surgery compared to the fixation with screws only.

Objective: To explore the relationship between adolescent depressive symptoms, childhood psychological trauma and maternal illness during pregnancy, so as to provide scientific busis for the development of adolescent mental health. Methods: A stratified cluster random sampling method was employed to select 2 092 primary and secondary school students in Wuhan City from January to July 2022. Questionnaires were administered to investigate adolescent depressive symptoms, childhood psychological trauma, and maternal illness during pregnancy. The influencing factors of adolescent depression were analyzed. Results: A total of 139 adolescents reported depressive symptoms. The childhood trauma questionnaire (CTQ) score of the depression group was (57.49± 6.85 ), and the score in adolescents without depression group was (46.28±5.96)( t =21.14, P <0.05). Among the maternal diseases during pregnancy, hypertension accounted for 11.51% , diabetes 9.35%, cholestasis 7.19%, hypothyroidism/hyperthyroidism 7.91% , anemia 9.35% and viral hepatitis 3.60% in depression group, 5.79%, 4.71%, 3.64%, 3.07%, 4.30%, 1.18% in the group without depression, respectively, and the differences were statistically significant ( χ 2=7.35, 5.87, 4.42, 9.28, 7.49, 5.75, P <0.05). The proportion of academic stress in the depressed group and non-depressed group were 61.15% and 46.34%, respectively, and was statistically significant ( χ 2=16.04, P <0.05). Multivariate Logistic regression analysis showed that gestational hypertension ( OR=5.04, 95%CI =2.07-12.24), diabetes mellitus ( OR=4.49, 95%CI =1.85-10.91), anemia ( OR=3.68, 95%CI =1.51-8.94), high academic stress ( OR=3.52, 95%CI =1.45-8.56) and the Childhood Trauma Questionnaire ( OR=4.63, 95%CI = 1.91 -11.26) were the risk factors of depression in adolescents ( P <0.05). Conclusion Adolescent depression may be due to high academic stress, childhood psychological trauma, maternal hypertension, diabetes, thyroid dysfunction and anemia in pregnancy. It is suggested that relevant departments provide appropriate measures to reduce the risk of adolescent depression.

Objective:To evaluate the clinical outcome of Robot-assisted sacroiliac screw fixation in the treatment of fragility fracture of the sacrum in the elderly.Methods:From March 2016 to June 2022, a retrospective analysis was performed on 30 patients with fragility fractures of the sacrum in the elderly who accepted robot-assisted sacroiliac screw to treat fragility fractures of the sacrum in our hospital. There were 12 males and 18 females with average age 71.03±8.25 years (range, 60-89 years). According to the classification of fragility fractures of the pelvis (FFP) in the elderly, there were 22 patients with FFP II, 2 patients with FFP III, and 6 patients with FFP IV. Surgical planning was based on the average CT value of S 1 channel and whether there is a transsacral screw channel. Robot-assisted sacroiliac screw fixation was performed during surgery. The pain of pre-operation and post-operation was evaluated using the visual analogue scale (VAS), the position of sacroiliac screws was evaluated by Gras grading, and the degree of functional recovery after surgery was evaluated using the Majeed function score. Results:All 30 patients successfully completed the operation. The mean operation time was 27.00±6.68 min (range, 18-35 min), the mean fluoroscopy times were 27.13±5.16 (range, 18-34), and the mean blood loss was 30.53±6.61 ml (range, 23-38 ml). All patients were followed up, and the mean follow-up time was 19.03±7.8 months (range, 8-25 months). The VAS was 5(5, 6), 4(3, 4), 3(2, 3), 0(0, 1) points before surgery, 1 week, 2 months and 6 months after surgery, respectively, and the difference was statistically significant ( H=103.26, P<0.001). After the surgery of 2 months, 6 months and the last follow-up time, the Majeed function scores were 88(83, 90), 91(87, 92), 92(90, 93) points, respectively, and the difference was statistically significant ( H=19.59, P<0.001). Screw position was evaluated according to Gras grading at 3 days after surgery, including 28 cases of level I, 2 cases of level II, and no screw penetrated the cortical bone or entered the sacral canal or sacral foramen. No vascular or nerve injury occured during the operation. 28 patients with FFS met the fracture healing criteria, and the healing time was 4.54±1.57 months (range, 3-7 months). Two patients had bone nonunion, one of whom underwent anterior ring plate removal due to infection of the pelvic anterior wound, and one month later, pelvic CT scan revealed loosening of the sacroiliac screw; the other one is considered to be related to too early weight bearing. Conclusion:For fragility fractures of the sacrum in elderly, Robot-assisted sacroiliac screw is an effective minimally invasive treatment, with high accuracy of screw placement, effective pain reduction, improved fracture healing rate, and achieve the satisfactory clinical efficacy.

Objective:To investigate the clinical efficacy of robot-assisted sacroiliac screw implantation in the treatment of proximal dysplasia sacral fractures.Methods:A retrospective analysis was conducted on 191 patients admitted to the Pelvic Department of Tianjin Hospital from May 2016 to January 2021 who underwent robot assisted sacroiliac screw implantation with sacral fractures, including 105 males and 86 females, aged 38.5±6.5 years (ranging from 19 to 69 years old). Among them, there were 85 patients with dysplasia of proximal sacrum. According to the classification of proximal sacral dysplasia, the patients were divided into five groups: the steep sacral alar slope group ( n=60), the mastoid protrusion group ( n=30), the lumbar sacralization group ( n=25), the sacral foramen oval degeneration group ( n=23) and the S 1 anterior cortical depression group ( n=10). The remaining 106 patients were normal group. Iliac cortical density (ICD) line typing was recorded in the 85 patients. The the completion of sacroiliac screw implantation, the Gras score of screw position after operation, the postoperative complications, the minimum diameter of S 1 screw channel (R1), the angle ∠A between the S 1 sacroiliac screw in the coronal plane and the cephalic side, and the angle ∠B between the S 1 sacroiliac screw in the water plane and the ventral side were recorded and compared with those of normal development patients. Results:The incidence of steep sacral alar slope was the highest (31.4%, 60/191). There were 2 or more developmental abnormalities in 24 cases. In 85 cases with dysplasia of proximal sacrum, ICD line type I was found in 8 cases, type II in 12 cases and type III in 65 cases. 49 patients (58.8%, 49/85) were able to complete the implantation of S 1 sacroiliac screw, while 36 patients (35.3%, 36/85) were only able to complete the implantation of S 2 sacroiliac screw. The Gras score of postoperative screw position was 90.05% for grade I, 9.94% for grade II, and 0 for grade III. In 1 case the sacroiliac screw pierced through the anterior cortex of the sacrum, and in 1 case the screw partially threaded into the sacral foramen, and there were no symptoms of iatrogenic nerve injury. The R1 values of the preoperative steep sacral alar slope group, the mastoid protrusion group, the sacral foramen oval degeneration group, the lumbar sacralization group, the sacral foramen oval degeneration group and normal development patient group were 11.4±3.0, 11.6±3.2, 9.8±3.0, 8.8±4.2, 6.5±4.4, and 11.4±3.4 mm, respectively. The differences between the lumbar sacralization group, the sacral foramen oval degeneration group, and the S1 anterior cortical depression group with the normal development patients were statistically significant, respectively ( t=-3.05, P=0.005; t=-2.32, P=0.022; t=-3.45, P=0.006). The postoperative angle ∠A of the above six groups were 33.8°±4.2°, 20.8°±3.5°, 25.8°±2.5°, 35.5°±4.5, 27.8°±3.5° and 26.8°±5.0°, respectively. The postoperative angle ∠B of the above six groups were 27.8°±3.5°, 36.2°±3°, 26.3°±1.8°, 29.8°±2.7°, 14.8°±1.5° and 37.2±4.2°, respectively. The differences between the ∠A of the steep sacral alar slope group, the mastoid protrusion group, and tthe lumbar sacralization group with that of the normal development patients were statistically significant, respectively ( t=9.17, -7.48, 7.97, P<0.001). The differences between the ∠B of the steep sacral alar slope group, the lumbar sacralization group, the sacral foramen oval degeneration group, and the S 1 anterior cortical depression group with that of the normal development patients were statistically significant, respectively ( t=-14.68, -10.93, -19.79, -35.8, P<0.001). Conclusion:This study proposes the "absolute stenosis" of the S 1 screw channel; In the treatment of patients with abnormal proximal sacral fracture, attention should be paid to S 1 anterior cortical depression and lumbar sacralization, and robot-assisted sacroiliac screw implantation can further improve the safety and accuracy of sacroiliac screw implantation.

The follow-up treatment of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation after drug resistance to EGFR-tyrosine kinase inhibitors (TKIs) have become a hotspot and difficulty at present. Immune checkpoint inhibitors (ICIs) therapy is a new and important choice for these patients, but many studies have shown unsatisfactory efficacy. However, some domestic and foreign studies have shown that ICIs combination therapy is still effective in some patients with positive driver genes and drug resistance after targeted therapy. So, in the era of immunotherapy, what are the differences in the efficacy of different combination immunotherapy strategies for different patients? What are the factors that affect efficacy? What are the interrelationships between these factors and other immunotherapy efficacy prediction biomarkers? All these problems have broad and important research value.
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Carcinoma, Non-Small-Cell Lung/genetics* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

BACKGROUND: Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring. METHODS: The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy. RESULTS: Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months. CONCLUSIONS The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.

BACKGROUND: Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers. METHODS: Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis. RESULTS: The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006). CONCLUSIONS In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.

Objective:To analyze the risk factors of deep venous thrombosis (DVT) in patients with tibial plateau fracture during preoperative period.Methods:From July 2017 to October 2019, a total of 264 patients undergoing surgeries of tibial plateau fractures were enrolled. Duplex ultrasonography (DUS) during hospitalization was used to screen for DVT of the bilateral lower extremities. Patients were divided into DVT group and non-DVT group according to results of DUS. Data on demographics, comorbidities, injury-related data, fracture type, laboratory biomarkers were collected and compared between groups with and without DVT.Results:The incidence of preoperative DVT was 39.0% (103/264) among 264 patients with traumatic tibial plateau fractures, and distal thrombosis predominated in DVT group. There were 103 cases in DVT group. 55 were males and 48 were females. The average age was 54.00±11.12. According to the Schatzker classification of tibial plateau fractures, 7 cases belonged to type I, 37 to type II, 2 to type III, 11 to type IV, 29 to type V, and 17 to type VI. There were 161 cases in non-DVT group. 89 were males and 72 were females. The average age was 48.57±13.25. According to the Schatzker classification of tibial plateau fractures, 23 cases belonged to type I, 76 to type II, 2 to type III, 10 to type IV, 33 to type V, and 17 to type VI. Univariate analysis showed that age ( t=3.451, P=0.001), the type of tibial plateau fracture ( χ2=8.314, P=0.004), D-dimer ( χ2=18.552, P<0.001), APTT ( t=2.869, P=0.004), ALB ( t=2.292, P=0.023) and Hb ( t=1.983, P=0.048) were statistically different than those in non-DVT group. Multivariate analysis showed age ( OR=1.033, 95% CI: 1.009, 1.058; P=0.007), the type of tibial plateau fracture ( OR=1.829, 95% CI: 1.014, 3.299; P=0.045) and D-dimer ( OR=1.914, 95% CI: 1.057, 3.464; P=0.032) were independent risk factors. Conclusion:The incidence of DVT in patients with tibial plateau fractures during preoperative period is high, and distal thrombosis is the main part of venous thrombosis of lower extremity. The type of tibial plateau fracture, age and the level of D-dimer are independent risk factors of preoperative DVT in patients with tibial plateau fractures.

BACKGROUND: The patients with advanced lung adenocarcinoma should select targeted drugs based on the type of tumor epidermal growth factor receptor (EGFR) gene mutation. However, it is difficult to collect tumor tissue of advanced lung adenocarcinoma, and some experts agree that peripheral blood can be used as a substitute for tumor tissue as a test specimen. This paper aimed to investigate the clinical value of ddPCR and super-amplification refractory mutation system (ARMS) in detecting EGFR gene mutation in peripheral blood of patients with advanced lung adenocarcinoma. METHODS: A total of 119 patients diagnosed in Beijing Chest Hospital Affiliated to Capital Medical University from February 2016 to February 2019 were collected, and the sensitivity and specificity of plasma ctDNA EGFR gene mutation detected by ddPCR and super-arms were compared. Some patients with positive EGFR gene mutations received oral treatment with first-line EGFR tyrosine kinase inhibitors (EGFR-TKI). The patients were divided into subgroups according to the test results. In group 1, both ddPCR and super-arms showed positive EGFR gene mutation results, with 21 cases. In group 2, ddPCR and super-arms detection of EGFR gene mutation were all negative, with 16 cases. In group 3, the ddPCR test was positive and the super-arms test was negative, with 5 cases. In group 4, the ddPCR test result was negative while the super-arms test result was positive. Since the number of patients in group 4 was 0, no statistics were included. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate the short-term outcome, and progression-free survival (PFS) was compared with survival analysis to evaluate the long-term outcome. RESULTS: EGFR mutations were detected in 58 (48.7%) of 119 patients with advanced lung adenocarcinoma. The coincidence rate between ddPCR and EGFR gene mutation in tumor tissues was 82.4% (Kappa=0.647, P<0.001), the sensitivity was 74.1%, and the specificity was 90.2%. However, the coincidence degree of super-arms test and tissue test was 71.4%, the sensitivity was only 58.6%, and the specificity was 83.6%. The ORR and DCR values in group 3 were lower than those in group 1 and 2, but there was no significant difference in ORR between groups (P>0.05). Survival analysis showed that the PFS of the three groups was compared. The difference was not statistically significant (χ²=2.221, P=0.329). CONCLUSIONS ddPCR, as a high sensitivity and specificity liquid gene detection method, can be used as a reliable method to detect the mutation of plasma ctDNA EGFR gene in patients with advanced lung adenocarcinoma. The results of plasma genetic testing can also be used as the basis for predicting the efficacy of EGFR-TKIs in patients.