Objective:To explore potential biomarkers that can predict the clinical efficacy of PD-1/PD-L1 inhibitors in malig-nancies.Methods:The PubMed,Web of Science,CNKI,Wanfang and VIP databases were searched from the establishment of the database to September 20,2022.After literature screening,data extraction and the risk of bias were evaluated independently by two evaluators,the Meta-analysis was performed using RevMan5.4 and STATA16.0 software.Results:This paper included 18 studies with a total of 4 018 patients.Tumor patients with a high tumor mutational burden(TMB)were found to have higher overall survival(OS)(P=0.003,P=0.01)and progression-free survival(PFS)(P=0.000 2,P=0.04)with PD-1/PD-L1 inhibitors within 1 year and 2 years of follow-up.At different follow-up times,with 1%as the critical value,there was no statistical significance in the level of PD-L1 ex-pression as a biomarker for predicting OS and PFS of PD-1/PD-L1 inhibitors(P>0.05).Conclusion:TMB can be used as a biological indicator to predict the clinical efficacy of PD-1/PD-L1 inhibitors in patients with malignant tumors within 2 years after treatment,but whether its efficacy can last longer remains to be further studied.PD-L1 single test is not currently a biomarker for predicting the bene-fit of PD-1/PD-L1 inhibitors.

Objective To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression. Results Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis. Conclusion Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Malignant tumor is a persistent disease that perplexes public health. Traditional treatment appears ineffective for patients with advanced metastasis. In recent years, immune checkpoint inhibitor therapy has developed rapidly and has great potential, but the overall clinical efficiency is still low. Carcinoma changes the tumor microenvironment through various mechanisms, resulting in immune resistance, which greatly reduces the efficacy of immune checkpoint inhibitors. Hyperthermia can not only play the anti-tumor advantage of thermal effect, but also play a direct and indirect immune sensitization effect through a variety of ways, transforming" cold tumor" into" hot tumor" , to enhance the impact of immune checkpoint inhibitors in many patterns. Numerous basic experiments have proved that hyperthermia combined with immune checkpoint inhibitors has achieved a classy impression in mice. Presently, some ongoing clinical trials of hyperthermia combined with immune checkpoint inhibitors have gained promising progress. In this paper, the merits of combination therapy were analyzed from three aspects: immune checkpoint inhibitors, hyperthermia, hyperthermia combined with immune checkpoint inhibitors, and the future research directions of hyperthermia combined with immune checkpoint inhibitors were prospected.

Objective:To investigate the effect of expanded polytetrafluoroethylene (E-PTFE) combined with autologous costal cartilage in rhinoplasty.Methods:Forty-two patients who underwent rhinoplasty in the form of E-PTFE combined with autologous costal cartilage in the Department of Plastic Surgery, Jiangsu Province Hospital of Chinese Medicine from January 2017 to December 2018 were selected as the research object. The polytetrafluoroethylene combined with autologous costal cartilage was used for rhinoplasty. The dorsal nasal skin was dissected through an inverted " V" type combined with subalar cartilage incision, and then the costal cartilage was cut into appropriate cartilage slices to build the nasal tip stent. According to the degree of elevation of the nasal dorsum, the sculpted E-PTFE was placed under the nasal dorsal fascia. The rectus abdominis fascia covered the apex of the nose, and the incision was closed by suture.Results:The nasal appearance of the forty-two patients was significantly improved, with good nasal shape and no serious complications. After 6-12 months of follow-up, 40 cases were satisfacted with the effect of the rhinoplasty, accounting for 95.2%.Conclusions:The use of polytetrafluoroethylene combined with autologous costal cartilage can effectively raise the dorsum of the nose, extend the length of the nose, project the nasal tip in the rhinoplasty. This procedure is accurate and safe, reach a favorable long-term shape and own high satisfaction, and it thus is worthy of popularization in clinic.

Objective:To investigate multimodality imaging characteristics and clinical features of lymphomatosis cerebri (LC) and reasons for misdiagnosis,with the goal of potentially facilitating an early and accurate diagnosis for this often-missed disease.Methods:Clinical data and cerebral multimodality imaging findings from 11 patients with LC proven basing on pathology in the Affiliated Hospital of Guizhou Medical University from November 30, 2011 to December 28, 2020 were retrospectively extracted, analyzed, and reviewed in combination with the literatures.Results:The common presenting symptoms with subacute onset included cognitive decline (8/11), gait disturbance (9/11), and behavioral disturbance (5/11). Test of cerebrospinal fluid showed that the number of cells and the level of protein increased (8/10), the sugar content (2/10) and chloride (4/10) decreased. The imaging manifestations of 11 patients with LC were diffuse lesions of bilateral cerebral white matter in the both deep and lobar lesion distribution, involving the cerebral cortex and subcortical white matter in eight cases (8/11), basal ganglia in seven cases (7/11), thalamus in five cases (5/11), cerebellum in six cases and brain stem in six cases (6/11). All 11 patients showed equal or slightly low-density shadows on CT plain scan and slightly longer T 1WI and T 2WI signals on magnetic resonance imaging. Six cases (6/11) had no obvious enhancement in the early stage, and five cases and six follow-up cases showed heterogenous spots, patches, nodules or clusters of distinct enhancement. Diffusion-weighted imaging showed non restricted diffusion in nine (9/11) cases initially diagnosed, and restricted diffusion in two cases (2/11) and nine follow-up cases, which were hyperintense on diffusion-weighted imaging and hypointense on apparent diffusion coefficient maps. Five patients (5/5) presented a marked decrease in N-acetyl aspartic acid (NAA)/creatine (Cr) and increase in choline (Cho)/Cr on hydrogen proton magnetic resonance spectrum, including an increase in lipid/Cr in three cases. One case (1/3) showed no abnormal increase in lesion metabolism, and two cases (2/3) showed slightly increased uptake on positron emission tomography/CT. Conclusions:Diffuse bilateral cerebral lesions especially in deep and lobar region, without enhancement or with patchy enhancement, marked decrease in NAA/Cr and increase in Cho/Cr and Lip/Cr are suggestive of LC. Misdiagnosis may be mainly due to insufficient understanding and improper brain biopsy.

Objective:To examine the early and mid-term results of coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) in the treatment of diffuse coronary artery stenosis.Methods:The clinical data and follow-up results of 248 patients who underwent CE+CABG surgery from January 2010 to January 2019 at Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University was analyzed retrospectively. There were 201 males and 47 females, aged (65.6±8.5) years (range: 43 to 79 years). The on-pump group included 156 patients and the off-pump group included 92 patients. CABG was performed after CE. CE was performed on 248 patients who represented 269 target coronary lesions, of which 108 were located on the left anterior descending artery and sub-branches, 140 were located on the right coronary artery and sub-branches, and 21 were located on the left circumflex artery and obtuse marginal artery. A total of 872 bypass grafts were performed, including 248 left internal thoracic arteries, 48 radial arteries, and 576 great saphenous veins, with (3.5±0.8) grafts (range:2 to 6 grafts) per patient.The grafts had satisfactory bridge blood flow after CE, with the graft flow rates of (26±8) ml/min (range: 13 to 59 ml/min) and the pulsatility index value of 3.1±0.8 (range: 2.0 to 6.7). The t test and χ 2 test was used to compare the surgical results and graft patency rate between patients in on-pump and off-pump group, respectively. Results:The number of graft vessels of on-pump group and off-pump group was 3.6±0.9 and 3.2±0.7, respectively( t=1.637, P=0.085). There were 3 deaths during the perioperative period, with a mortality rate of 1.2%. Two people died of renal failure, and one case was due to postoperative refractory low cardiac output. Perioperative myocardial infarction occurred in 9 cases. The follow-up time was (41.8±21.4) months (range:1 to 68 months). The all graft patency rate was 78.4%(812/232) in 1 year and 69.8%(162/232) in 3 years postoperatively. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate(1-year: 87.4% vs.73.1%, χ2=6.533, P=0.011, 3-year: 78.2% vs. 64.8%, χ2=4.588, P=0.032). There was no significant difference in graft patency rates between the on-pump group and off-pump group (1-year: 80.0% vs. 76.9%, χ2=0.277, P=0.599, 3-year:71.5% vs. 67.9%, χ2=0.300, P=0.584). Conclusions:CE+CABG is a safe and feasible technique for patients with diffuse coronary artery disease to get more satisfied complete revascularization, with good early and medium-term results and graft patency rates. The outcomes of on-pump or off-pump CE+CABG are similar.

Objective:To explore the impact of occupational stress and shift work on the mental health of railway workers and provide a scientific basis for occupational health protection.Methods:In April 2019, stratified cluster sampling method was used to select 613 railway workers from Fuzhou railway as subjects. Job Content Questionnaire (JCQ) , Symptom Checklist-90 (SCL-90) , Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were used to investigate railway workers' occupational stress and mental health conditions. The influencing factors of railway workers' mental health were analyzed.Results:The detection rates of mental health problems, anxiety and depression of railway workers were 40.5% (248/613) , 4.4% (27/613) and 9.0% (55/613) , respectively. There were 250 railway workers with occupational stress (40.78%) . There were statistically significant differences in the total scores of SCL-90 among different groups of working age and education background ( P<0.05) . And there were statistically significant differences in the SAS total scores among different groups of education background ( P<0.05) . The detection rates of mental health problems and anxiety in the night shift group were higher than that in the white shift group, and the differences were statistically significant ( P<0.05) . The detection rate of mental health problems in the group with occupational stress was higher than that in the group without occupational stress, and the difference was statistically significant ( P<0.05) . Logistic regression analysis found that night shift work was the main risk factor affecting railway workers' anxiety ( OR=2.38, 95 %CI: 1.04-5.46, P<0.05) . The results of interaction analysis showed that compared with the non-occupational stress+white shift group, the workers in the night shift+occupational stress group had the higher risk of mental health problems and anxiety ( OR=3.14, 95 %CI: 1.84-5.38; OR=4.29, 95 %CI: 1.36-13.54; P<0.05) . Conclusion:Night shift and occupational stress are the risk factors for the mental health of railway workers, and the interaction between night shift and occupational stress is the most harmful to the mental health of railway workers.

Objective:To examine the early and mid-term results of coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) in the treatment of diffuse coronary artery stenosis.Methods:The clinical data and follow-up results of 248 patients who underwent CE+CABG surgery from January 2010 to January 2019 at Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University was analyzed retrospectively. There were 201 males and 47 females, aged (65.6±8.5) years (range: 43 to 79 years). The on-pump group included 156 patients and the off-pump group included 92 patients. CABG was performed after CE. CE was performed on 248 patients who represented 269 target coronary lesions, of which 108 were located on the left anterior descending artery and sub-branches, 140 were located on the right coronary artery and sub-branches, and 21 were located on the left circumflex artery and obtuse marginal artery. A total of 872 bypass grafts were performed, including 248 left internal thoracic arteries, 48 radial arteries, and 576 great saphenous veins, with (3.5±0.8) grafts (range:2 to 6 grafts) per patient.The grafts had satisfactory bridge blood flow after CE, with the graft flow rates of (26±8) ml/min (range: 13 to 59 ml/min) and the pulsatility index value of 3.1±0.8 (range: 2.0 to 6.7). The t test and χ 2 test was used to compare the surgical results and graft patency rate between patients in on-pump and off-pump group, respectively. Results:The number of graft vessels of on-pump group and off-pump group was 3.6±0.9 and 3.2±0.7, respectively( t=1.637, P=0.085). There were 3 deaths during the perioperative period, with a mortality rate of 1.2%. Two people died of renal failure, and one case was due to postoperative refractory low cardiac output. Perioperative myocardial infarction occurred in 9 cases. The follow-up time was (41.8±21.4) months (range:1 to 68 months). The all graft patency rate was 78.4%(812/232) in 1 year and 69.8%(162/232) in 3 years postoperatively. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate(1-year: 87.4% vs.73.1%, χ2=6.533, P=0.011, 3-year: 78.2% vs. 64.8%, χ2=4.588, P=0.032). There was no significant difference in graft patency rates between the on-pump group and off-pump group (1-year: 80.0% vs. 76.9%, χ2=0.277, P=0.599, 3-year:71.5% vs. 67.9%, χ2=0.300, P=0.584). Conclusions:CE+CABG is a safe and feasible technique for patients with diffuse coronary artery disease to get more satisfied complete revascularization, with good early and medium-term results and graft patency rates. The outcomes of on-pump or off-pump CE+CABG are similar.