【Objective】 To analyze the correlation of whole body tumor burden of ¹⁸F-prostate specific membrane antigen positron emission computed tomography （¹⁸F-PSMA PET/CT） with prostate specific antigen （PSA） and Gleason score so as to evaluate the value of ¹⁸F-PSMA PET/CT whole body tumor burden for predicting serum PSA progression in prostate cancer. 【Methods】 We retrospectively recruited 213 patients with prostate cancer who underwent ¹⁸F-PSMA PET/CT scanning from March 2019 to April 2021. The serum PSA and Gleason score were collected. Whole body tumor burden was measured by a semi-automatic method. The correlation of tumor burden with serum PSA and Gleason score was analyzed. After radical prostatectomy， the patients were divided into groups according to negative or positive ¹⁸F-PSMA PET/CT. PSA differences between groups were compared， and the receiver operating characteristic curve （ROC） of the subjects was drawn so as to obtain the threshold value of PSA to predict the positive rate of ¹⁸F-PSMA PET/CT. The patients were followed up for PSA after radical surgery， divided into groups according to the progress of PSA， and the differences in tumor burden between groups were compared. 【Results】 In Gleason score ≤7， =8， and ≥9 groups， whole body tumor burden was correlated with PSA in each group （P=0.001）， and tumor burden significantly differed between the groups （P<0.001）. In initial diagnosis and treatment group， biochemical recurrence group， and medication group， the correlation between tumor burden and PSA was statistically significant （P=0.001）. The Gleason score of primary prostate lesion was significantly correlated with systemic tumor burden （P<0.001）. The area under ROC curve of PSA predicting the positive rate of ¹⁸F-PSMA PET/CT after radical prostatectomy was 0.821； when PSA>0.577 ng/mL， the sensitivity and the specificity were 66.7% and 96.8%， respectively. The mean whole body tumor burden in ¹⁸F-PSMA PET/CT positive patients with PSA progression was higher than that in patients without PSA progression. 【Conclusion】 The whole body tumor burden of ¹⁸F-PSMA PET/CT is significantly correlated with PSA， which is helpful in predicting the serum PSA progression in prostate cancer. PSA can predict the positive rate of ¹⁸F-PSMA PET/CT to a certain extent. At the same time， PSA can also predict positive results of ¹⁸F-PSMA PET/CT to a certain extent， and guide clinical rational selection of this examination.

【Objective】 To investigate the value of prostate-specific antigen （PSA） level， Gleason score， and PSMA PET/CT maximum standardized uptake value （SUVmax） in predicting prostate cancer （PCa） metastasis and the treatment option of oligometastatic PCa. 【Methods】 We retrospectively recruited 170 patients with PCa confirmed by pathology， 97 of whom were untreated， and divided them into nonmetastatic group， oligometastatic group （metastasis≤5）， and polymetastatic group. In addition， 28 patients with oligometastatic PCa underwent radical prostatectomy and 45 patients underwent androgen-deprivation therapy. We compared the differences in SUVmax， PSA， and Gleason scores between the three sub-groups of untreated patients， and also analyzed the correlation between SUVmax of local cancer lesions， Gleason score and PSA level. We further compared the differences in SUVmax and PSA levels between radical prostatectomy and androgen-deprivation therapy of oligometastatic PCa patients. According to Gleason score， patients with oligometastatic PCa were divided into two groups （low-intermediate risk group with Gleason score ≤7 and high-risk group with Gleason score ≥8）， and the levels of SUVmax and PSA between the groups were compared. 【Results】 With the increasing number of metastases， SUVmax， PSA levels and Gleason scores all showed an upward trend， and there were significant differences among the three groups （P=0.029， P=0.001， P=0.046）. The post-hoc test found significant difference in Gleason score between the oligometastatic group and the other two groups （P=0.043， P=0.002） as well as correlation of SUVmax level of the primary tumor with Gleason score and PSA （P=0.002， r=0.315； P<0.001， r=0.430）. There was significant difference in PSA level between the two groups after radical prostatectomy and androgen-deprivation therapy （P=0.017）. The difference in PSA between the two treatments persisted in the low-intermediate risk groups （P=0.021）. 【Conclusion】 PSA level， Gleason score and SUVmax have some value in predicting PCa metastasis. Radical prostatectomy is an effective treatment strategy for patients with oligometastatic PCa， especially those with low-intermediate Gleason score.

Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.

Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.

Objective: To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD). Methods: Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV₁) in the predicted value, FEV₁/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve. Results: The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV₁/FVC, the percentage of FEV₁ in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively. Conclusion S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.

Objective:To investigate the drug-resistant mutations of human immunodeficiency virus-1 (HIV-1) in patients who received highly active antiretroviral therapy (HAART) from 2014 to 2018.Methods:A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled. Plasma samples were collected, and one-step reverse transcription-polymerase chain reaction (PCR) and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region. The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis. Viral genotyping tool software was used to analyze HIV-1 subtype distribution. The categorical variables were compared using chi-square test. Results:Among 880 patients, the plasma HIV-1 viral load was (4.12±0.63) lg copies/mL, the CD4 + T lymphocyte count was (251±124)/μL, and the median duration of antiviral therapy was 26 months. In the subtypes analysis, the circulating recombinant form (CRF) 01-AE subtype was the largest proportion of HIV-1 subtypes, accounting for 38.9%(342/880), and the CRF07-BC subtype accounted for 28.5%(251/880), B+ C subtypes accounted for 16.2%(143/880). Drug-resistant mutations were detected in 534 patients, with a total drug resistance rate of 60.7%. The drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) were 51.0%(449/880), 58.6%(516/880) and 1.7%(15/880), respectively. The drug resistances to lamivudine, emtricitabine, efavirenz, and nevirapine were serious, and the medium/high resistance rates were 46.8%(412/880), 46.8%(412/880), 51.3%(451/880), and 53.6%(472/880), respectively, while those to zidomidudine (6.0%, 53/880), etravirin (9.0%, 451/880) and PI were not serious. M184IV (47.3%), K65R (22.2%) and K70RE (12.6%) were the most frequent mutations for NRTI. K103NS (25.1%), V106A (19.7%) and V179DE (14.4%) were the most frequent mutations for NNRTI. The most common drug-resistant mutations for PI were L10FIV (7.4%) and A71IVT (6.5%). The drug resistance rate of CRF01-AE subtype (69.3%, 237/342) was higher than those of CRF07-BC subtype (49.8%, 125/251) and B+ C subtype (51.0%, 73/143), the differences were statistically significant ( χ2=22.6 and 14.6, respectively, both P<0.05). Conclusions:The incidence of drug resistance is high among HIV-1 infected patients after six-month HAART treatment in Chongqing City. The drug resistance to NNRTI is the most common, followed by NRTI, while PI is less resistant. Drug resistance is the main reason for the virological breakthrough in HIV-1 infected patients.

Objective:To explore the advantages of the novel individualized 3D printing artificial vertebral body in spine reconstruction and to evaluate its clinical effect.Methods:From January 2017 to December 2018, the 15 patients who underwent total vertebrectomy and spine reconstruction with individualized 3D printing artificial vertebral body were analyzed retrospectively. There were 8 males and 7 females, with the mean age 39.5 years (range: 20-57), including 12 primary tumors and 3 metastatic tumors. According to tumor location and surrounding soft tissue invasion range, simple posterior or combined anterior and posterior approach were used for total vertebral resection, and the defection was reconstructed by 3D printing artificial vertebral body. The operation time, intraoperative bleeding volume, postoperative stability of artificial vertebral body and bone ingrowth of adjacent vertebral body, preoperative and postoperative neurological changes, preoperative and postoperative VAS score, local control and survival of patients were analyzed.Results:The mean operation time was 412.0 min (range: 135-740 min), and the mean blood loss was 4 140.0ml (range: 100-14 000 ml). The mean follow-up time was 23.2 months (range: 12-35 months), and no one loss to follow-up. One case had pleural rupture, one case had cerebrospinal fluid leakage and one case had L5 nerve root palsy. All patients recovered after active symptomatic treatment. Compare with the preoperative VAS score (4.7±1.1), the differences of VAS score at 7 d postoperative and last follow-up (1.6±0.6 and 1.0±0.5) were significantly reduced ( P<0.001). Three patients with Frankel grade C gradually recovered to grade D, and no change were found in grade D and Grade E patients, there was no significant improved at last follow-up. Preliminary bone growth was found between the artificial vertebral body and the adjacent vertebral body 3 months after operation. The bone growth was more obvious at 12 months post-operation, and the artificial vertebral body fused with the adjacent vertebral bodies to form bone integration. At 24 months post-operation, the integration of the artificial vertebral body was more accurate. During the follow-up period, there was no loosening or displacement of the artificial vertebral body and no failure of internal fixation. A case of hemangioendothelioma and a case of epithelioid angiosarcoma died at 33 months and 35 months postoperatively. One patient with chondrosarcoma had local recurrence at16 months post-operation. After treated with arotinib, the tumor did not progress. The other 12 patients had no tumor recurrence or distant metastasis. Conclusion:After spinal tumor resection, individualized 3D printing artificial vertebral body can be used to accurate restoration of spinal continuity, and provide nice interface matching and bone growth between artificial vertebral body and the adjacent vertebral endplates. Moreover, the immediate and long-term stability of the artificial vertebral body can meet the needs of spinal reconstruction.

Objective To study the safety and feasibility of laparoscopy combined with holmium laser in the treatment of chronic pancreatitis complicated with pancreatic ductal stones.Methods To compare the clinical data in patients who underwent laparoscopy combined with holmium laser (10 patients,group A) with those who underwent laparoscopy only (21 patients,group B) at Zhejiang Provincial People' s Hospital from January 2012 to August 2018.The operation time,intraoperative blood loss,intraoperative conversion rate,pancreatic ductal incision length,postoperative pancreatic fistula rate,length of postoperative hospital stay,residual stone rate and relief of postoperative abdominal pain rate of the two groups were documented and analyzed.Results Three of 31 patients were converted to open surgery.The remaining patients in the two groups were discharged home without any perioperative death.Group A and B were significant differences in the pancreatic ductal incision length (5.0±0.8 vs.6.5±1.0) cm,operation time (289.3±51.6 vs.349.5± 34.7) min,and postoperative hospital stay (8.0± 1.2 vs.10.2± 1.6) d between the two groups (P＜0.05).There were no significant differences in the intraoperative conversion to open rate,intraoperative blood loss,postoperative pancreatic fistula rate,residual stone rate and relief of postoperative abdominal pain rate between the two groups (P ＞ 0.05).Conclusions It was safe and feasible to treat chronic pancreatitis complicated with pancreatolithiasis by laparoscopy.Laparoscopy combined with holmium laser had the added advantages of easy access through the pancreaticojejunostomy,shorter operation time,and less intraoperative blood loss.

Objective     To analyze the risk factors of atrial fibrillation (AF) after radical esophagectomy, providing the basis for prevention and treatment of AF after radical esophagectomy. Methods     We conducted a retrospective analysis of 335 patients' clinical data, who accepted laparoscopic combined thoracic or open radical esophagectomy in the same treatment group at Department of Thoracic Surgery of Shengjing Hospital of China Medical University between January 2014 and August 2016. There were 262 males and 73 females at age of 65.1 (43-78) years. Results     There were 48 of 335 patients with AF within 1 week after surgery. By univariate analysis: age, gender, history of peripheral vascular disease and cardiac stents or angina pectoris, preoperative brain natriuretic peptide (BNP), preoperative left ventricular diastolic dysfunction, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion were possible risk factors. By multivariate analysis: age, gender, history of cardiac stents or angina pectoris, preoperative BNP, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion were risk factors. Conclusion     The risk factors of AF after radical esophagectomy are age, gender, history of cardiac stents or angina pectoris, preoperative BNP, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion. Perioperative positive intervention to above factors may reduce the incidence of postoperative AF.

Objective RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, was synthesized for investigating the function and mechanism of S1PR3 in bacterial clearance. Methods Measure the ability of RY-15 with FITC to enter the THP-1 cell after coculture for 5 min, 10 min, 20 min, 30 min through confocal microscopy. The function of GY-5 and RY-15 in bacterial clearance was observed by gentamicin protection test. The phosphorylation level of ERK and p-ERK in THP-1 cell was detected by Western Blot after GY-5 and RY-15 stimulation for different times. Results According to confocal microscopy, RY-15 started to enter the THP-1 cell after stimulating for 10 min and the effect of entering cell was very obvious after stimulating for 30 min. Compared to GY-5 group, live bacteria in the macrophage were largely decreased in the RY-15 group( P<0.05). Conmpared to GY-5 group, the p-ERK level raised largely at different poins. Conclusions RY-15, a specific agonist of Sphingosine 1-phosphate Receptor 3, can promote bacterial clearance through entering cell and the phosphorylation level of ERK is a possible mechanism.