Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Objective To investigate the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters in evaluating the short-term prognosis of laryngeal cancer patients after postoperative radiotherapy.Methods A case-control study was performed on 127 laryngeal cancer patients admitted to our hospital from January 2021 to December 2023.The patients underwent different tumor treatment followed by radical radiotherapy.According to tumor recurrence or not,they were divided into a recurrence group(n=50)and a non-recurrence group(n=77).DCE-MRI parameters,such as volume transfer constant(Ktrans),rate constant(Kep),and volume fraction of extracellular extravascular space(Ve),and clinical data were compared between the 2 groups.Multivariate logistic regression analysis was used to identify influencing factors for short-term prognosis after radiotherapy.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive efficacy of DCE-MRI parameters,and the area under the curve(AUC)was calculated.Results The recurrence group had significantly larger proportions of positive surgical margins,preoperative maximum lesion diameter≥4 cm,ulcerative lesions,stages N1～N3,and advanced stages Ⅲ～Ⅳ,and obviously higher Ktrans and Kep values but lower Ve valus than the non-recurrence group(P<0.05).Multivariate logistic regression analysis indicated that positive surgical margins,stages N1～N3,Ktrans,and Kep were independent risk factors for short-term prognosis,while Ve was a protective factor(P<0.05).ROC curve analysis showed that the AUC value of combination of Ktrans,Kep and Ve and of above 5 indicators in predicting short-term prognosis of postoperative radiotherapy for laryngeal cancer was 0.920(95%CI:0.858～0.961)and 0.923(95%CI:0.862～0.963),respectively.Though the AUC value of combined 3 parameters was significantly higher than that of the single indicator alone(P<0.05),there was no difference in the value between the combination of 3 parameters and the combined application of the 5 indicators.Conclusion DCE-MRI parameters Ktrans,Kep,and Ve are closely associated with short-term prognosis of postoperative radiotherapy for laryngeal cancer.Their combination has a good predictive efficacy for the short-term prognosis of the patients.

Objective To compare and analyze the efficacy and risks of percutaneous CT/ultrasound-guided bipolar radiofrequency ablation(RFA)under local anesthesia with robotic-assisted laparoscopic partial nephrectomy(RAPN)for the treatment of sporadic small renal mass.Methods A retrospective study was conducted on 93 consecutive patients with T1a stage small renal mass during Mar.2019 and Oct.2021.Among them,51 underwent RAPN,and 42 underwent RFA.General information,tumor characteristics,perioperative and follow-up data were collected and statistically analyzed.Results There were no significant differences in general information and tumor characteristics between the two groups(P＞0.05).The operation time[(96.0±20.0)min vs.(113.5±24.1)min,P＜0.001],hospital stay[(3.5±0.8)day vs.(6.9±1.8)day,P＜0.001],and hospital costs[(2.4±0.7)ten thousand yuan vs.(6.6±0.4)ten thousand yuan,P＜0.001]were significantly decreased in the RFA group than in the RAPN group.There were no significant differences in the incidence of perioperative complications and long-term disease-free survival rate between the two groups(P＞0.05).However,the difference between one-year postoperative estimated glomerular filtration rate(eGFR)and preoperative eGFR was significantly lower in the RFA group than in the RAPN group[-2.3(-4.7-1.3)mL/(min·1.73 m2)vs.-5.0(-9.1 2.8)mL/(min·1.73 m2),P=0.003],and the reduction of one-year postoperative creatinine and preoperative creatinine was slightly lower in the RFA group than in the RAPN group[4.0(-0.2-5.5)μmol/L vs.4.5(1.8-9.2)μmol/L,P=0.122].Conclusion RFA can achieve comparable disease-free survival rate as RAPN in the treatment of T1a renal tumor,and can effectively preserve renal function,reduce medical costs,save medical resources,and lower the incidence of perioperative complications.

Objective　To investigate the microstructure changes of brain regions of interest in patients with Parkinson disease with dysosmia using diffusion kurtosis imaging.Methods　DKI scanning was performed in 16 patients with dysosmia and 21 patients without dysosmia.Supramarginal gyrus,postcentral gyrus,heschl gyrus and inferior temporal gyrus were selected as regions of interest.Results　The values of FA,KFA,AK and RK in the region of interest in the Parkinson disease group with dysosmia were significantly lower than those without dysosmia (P<0.05);the values of AD,MD and RD in the region of interest in the Parkinson disease group with dysosmia were significantly higher than those without dysosmia (P<0.05);There was a close correlation between the olfactory score and the right supramarginal gyrus,postcentral gyrus,inferior temporal gyrus,bilateral heschl gyrus in the Parkinson disease group with dysosmia (P<0.05).Conclusion　DKI parameters can be used as biomarkers for early diagnosis of dysosmia in Parkinson disease.

Objective: To investigate the effect of tripartite motif containing 59(TRIM59) on the biological function of human colorectal cancer HCT116 cells and its possible mechanism. Methods: The recombinant TRIM59 interference plasmid(si-TRIM59) was constructed and transfected into colorectal cancer cell line HCT116 by liposome transfection. The transfection efficiency was verified by RT-qPCR and Western blot. The effects of TRIM59 gene silencing on the proliferation, colony-formation ability and cell cycle of colorectal cancer cells were detected by CCK-8 method, colony formation assays and flow cytometry respectively. Western blot was used to detect the expression level of CDK4 and cyclinD1. Results: The expression levels ofTRIM59mRNA and protein in colorectal cancer cells were significantly higher than those in normal colorectal mucosa cells(P<0. 05). After knockdown of TRIM59expression, the proliferation activity and colony forming ability of HCT116 cells were significantly inhibited(P<0. 05), and the cell cycle was arrested in G0/G1 phase. At the same time, the expression levels of CDK4and CyclinD1 significantly decreased(P<0. 05). Conclusion TRIM59was highly expressed in colorectal cancer cells. Down regulation ofTRIM59expression can inhibit the proliferation and clone formation of colorectal cancer cells, suggesting thatTRIM59may become a new target for gene therapy of colorectal cancer.

Objective: To report the experience on the multi-disciplinary management of metastatic renal cell (mRCC) patients in a single center. Methods: Data of 168 mRCC patients treated by multi-disciplinary team (MDT) at Sun Yat-sen University Cancer Center from December 2007 to February 2019 was retrospectively analyzed.Three treatment groups were identified, including 76 patients with 55 males and 21 females, received anti-angiogenic agents alone (Group A), 66 patients with 55 males and 11 males, received anti-angiogenic agents plus local therapy (Group B)and 26 patients, with 19 males and 7 females, received anti-angiogenic agents plus immunotherapy and local therapy (Group C). The Sunitinib, Sorafenib, Axitinib were chosen for the TKI. The Pembrolizumab was used for immunotherapy. The stereotactic body radiation therapy and surgical excision were considered as the local therapy. The study aims to compare the age, gender, IMDC score, pathology, nbephrectomy, adverse events, progression-free survival and overall survival (OS). Results: Of all patients, the median follow-up duration was 23 months (ranging 6-117 cmonths). The PFS was 18.3 months and median OS was 33.5 months. The 2 years and 5 years survival rate was 66% and 35%, respectively. The median OS of Group A, B and C were 29.8 months, 44.6 months and not reached. 2y-OS was 58%, 67% and 89%, while 5y-OS 12%, 46% and 57%.There was no difference in age, gender, IMDC score, pathology, synchronous metastases or nephterectomy between the three groups. The prognostic result in TKI based combination therapy was superior to TKI therapy alone, which the 5y-OS was 51% and 11%, respectively. The prognostic result in group C's moderate-high risk mRCC patients was superior to group A and B. The median OS in TKI+ DC and CIK+ Pembrolizumab was 49.1 months and 53.1 months. On univariate analyses, IMDC score, nephrectomy and treatment group was associated with OS (P<0.05). On multivariate analyses, treatment group, nephrectomy was associated with OS (P<0.05). The risk of death of Group C decreased about 60% [HR 0.39 (0.17, 0.89), P=0.026]. 78 (46.4%) patients on TKI alone and 16 (61.5%) patients treated with TKI plus immunotherapy had Grade 3 or 4 adverse events. 16 (20.3%) patients had Clavien Ⅲ-Ⅳ toxicity after surgical procedures. 6 (5.7%) patients had Grade 3 toxiciy after SBRT. Conclusions Patients treated with combined therapy had better survival than those treated with anti-angiogenic agents alone. MDT approach could bring survival benefit to mRCC patients.

Objective To genotype mixed samples with next generation sequencing and evaluate its prospects in forensic DNA application. Methods Three mixed biological samples from rapes cases and their reference samples were collected. DNA was extracted using the MagAttract M48 DNA Manual Kit(200). The ForenSeqTMDNA Signature Prep Kit was used for library preparation, and next generation sequencing was performed on the MiSeq FGx system. The ForenSeqTMUniversal Analysis v1.2.1 software was used for data analysis. NGS-based STR results were compared with CE-based genotypes. Results A single length polymorphic STR allele in the mixed profile could be recognized as two sequence polymorphic STR alleles from different donors, which would assist mixed profile analysis. Such phenomenon was observed in D3S1358, D9S1122 and D13S317 in this work. Conclusion Our results suggested that precision STR genotyping of mixed samples based on NGS can provide more information and hints for mixed STR profile separation.

Objective To explore the relationship between blood lipid level and primary open angle glaucoma(POAG)and intraocular pressure(IOP).Methods A retrospective case-control study was designed.80 POAG patients from EYE & ENT hospital of FUDAN university were collected as a case group from January 2015 to May 2016.Meanwhile 80 age and gender matched healthy people were collected as a control group.The differences of gender in men subgroup (POAG:44,Control:39) and female subgroup (POAG:36,Control:41) showed no statistic significance.Serum total cholesterol(TC),total triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein A(Apo A) and apolipoprotein B(Apo B) were measured using Roche automatic biochemical analyzer.The analysis of the above mentioned lipid levels between POAG group and control group was conducted by independent student′s T test and multivariate logistic regression.The relationship between lipid level and IOP was analysied using Pearson correlation test.Results The TG level was (1.40±0.71)mmol/L in the POAG group,(1.00±0.37)mmol/L in the control group.The difference had statistic significance (t=4.467,P<0.001).The HDL-C level in the POAG group was (1.22±0.36)mmol/L,(1.38±0.25)mmol/L in the control group.The difference also had statistic significance (t=-3.228,P=0.002).Comparison between the men subgroup and female subgroup found that the TG level in the POAG group of men was (1.47±0.71)mmol/L,(1.01±0.36) mmol/L in the control group and the HDL-C level were (1.14±0.31) mmol/L,(1.32±0.20)mmol/L in two groups.Both the level of TG and HDL-C had statistic significance in men (t=3.717,P<0.001;t=-3.240,P=0.002).The TC,TG level in the POAG group and control group of women respectively were (4.59±0.81)mmol/L,(1.33±0.72)mmol/L and (4.21±0.64)mmol/L,(0.99±0.38)mmol/L.Both blood level were significantly higher than the control group in women (t=2.278,P=0.026;t=2.503,P=0.016).Logistic regression analysis showed that the TG level correlated with POAG (P=0.004,OR=2.831,95% CI=1.392-5.759)and both POAG in the men and women (P=0.025,OR=3.223,95% CI=1.156-8.989;P=0.045,OR=2.554,95% CI=1.020-6.395).Pearson test showed that the TG level of POAG patients was positively associated with IOP in spite of gender(P<0.05).Conclusion The peripheral blood level of TG was significantly increased in the POAG patients and significantly correlated with IOP,which indicated that the increased peripheral blood level of TG may be the independent risk factor for the POAG..

Objective In order to explore the association between complement C3 and primary open angle glaucoma (POAG),the serum complement C3 level was detected and the polymorphism of the C3 exon gene was analyzed in patients with POAG.Methods A prospective case-control study was designed.A total of 45 patients with POAG visiting Eye &ENT hospital of Fudan University were collected from December 2014 to December 2015,and 45 age-/gender-matched healthy subjects from yearly health screening were collected as normal controls.Serum C3 concentration was detected by immunoturbidimetric assay.Meanwhile,genomic DNA was extracted from peripheral blood leukocytes,and sequencing for C3 exons was followed with PCR to analyze the gene polymorphism.Statistical analysis was performed by use of SPSS 20.0 software.Student's t test was used to evaluate the difference of serum C3 level between two groups.Chisquare test was used to analyze the difference in the distribution of C3 exon gene polymorphism between two groups.The one-way ANOVA was utilized to analyze the difference of serum C3 level among different genotypes of C3 exon.Results The serum level of C3 in POAG (104.81 ± 29.15)mg/dl was significantly lower (t =-3.162,P =0.002) compared to controls (121.06 ± 18.39) mg/dl.There were a total of seven single nucleotide polymorphisms (SNPs) (rs2230201,rs2230204,rs2230205,rs428453,rs423490rs7951,rs539822147) within the C3 exon gene region,but no mutation was detected.There was no difference in the frequency and distribution of these SNPs between POAG and controls,as well as,there was also no significant difference in serum C3 level among these SNPs genotypes.Conclusions Decreased serum C3 level in POAG patients indicated that complement C3 might be involved in the pathomechanism of glaucoma.No significant abnormality of C3 exon gene was detected,so the gene polymorphism having an impact on serum C3 level could be excluded as a reason probably.

Objective To evaluate the safety and efficacy of the modified subclavian vein cathetrization (SVC) in Neurosurgical Intensive Care Unit (NICU).Methods The clinical data of 292 patients experienced SVC in NICU over a 3-year-and-9-month periodwere retrospectively analyzed,and they were divided into groups by the method of SVC,in which 227 patients underwent modified SVC were identified and compared with 65 patients who underwent routine SVC during the same period.Medical charts of the patients were reviewed to collect demographic information,such as age,sex,rate of success at first-puncture and complications.Statistical comparisons between the two groups were made using Chi-square analysis for the variables and were considered to be statistically significant if P ＜ 0.05.Data were analyzed using SPSS 19.0 (Armonk,NY:IBM Corp,USA).Results In the SVC group,the total success was achieved in 61 patients (93.8％),and the incidence rate of complications related to puncture and cathetrization was 29.5％.In the mSVC group,the total successful rate was 99.1％,and the incidence rate of complications related to puncture and cathetrization was 7.1％.The mSVC was better than traditional SVC in successful rate and incidence rate of complications related to puncture and cathetrization (x2 =4.61,7.32,all P ＜ 0.05).Conclusion mSVC for the patients in NICU is a safe and effective technique with low morbidity and mortality.