177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Clinical data of a child with mevalonic aciduria (MA) who underwent stem cell transplantation (SCT) in the Department of Rheumatology and Immunology, Children′s Hospital, Capital Institute of Pediatrics in March 2019 were retrospectively analyzed.A girl aged 2 years and 11 months old presented with recurrent fever for 2 years and 11 months and swelling of both knees for 9 months was enrolled.The child also had specific facial features and development delay.The urinary mevalonic acid and inflammatory factor levels were increased.The whole exome sequencing showed compound heterozygous mutations c. 439G>A (p.A147T) and c. 976G>A(p.G326R) in the MVK gene.After achieving a partial remission following the treatment of Tocilizumab, the patient was treated with SCT and thus yielded the complete remission.Through literature review of a total of 39 children with MA, most of cases suffer MA since the infancy.All systems can be affected by MA.Clinical manifestations of the nervous system abnormalities, recurrent fever, hepatosplenomegaly, delayed physical development, gastrointestinal symptoms, and eye involvement were helpful for the diagnosis of MA.To date, 10 cases (including one case in this study) of MA have been reported to receive SCT after achieving a partial remission of other treatment, and 7 finally achieve a complete remission.This case report provided references that SCT is an effective treatment to children with MA who fail to achieve a complete remission after conventional treatment.

Objective:To investigate the effect of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3) inflammasome on the proliferation and apoptosis of human retinal pigment epithelial cell line ARPE-19 exposed to high glucose and its mechanism.Methods:ARPE-19 cells cultured in vitro were divided into normal control group and high-glucose group, and were cultured in conventional medium and medium containing 30 mmol/L glucose for 48 hours, respectively.The content of reactive oxygen species (ROS) were detected by fluorescent probe, and the activity of superoxide dismutase (SOD) and the concentration of malondialdehyde (MDA) were tested by biochemical assay.The cells of the two groups were cultured with 0, 2, 5, 10, 15 and 20 μmol/L NLRP3 inhibitor CY-09 for 48 hours, respectively.The proliferation rate of ARPE-19 cells under various concentrations of CY-09 treatment was detected by cell counting kit-8, and the appropriate concentration of CY-09 was determined.ARPE-19 cells were divided into normal control group, normal+ CY-09 group, high-glucose group and high glucose+ CY-09 group.The culture medium in the normal+ CY-09 group and high glucose+ CY-09 group was supplemented with 15 μmol/L CY-09.Flow cytometry was used to detect the apoptosis rate of each group, and Western blot was used to detect the relative expression levels of NLRP3, apoptosis-associated point protein (ASC), Caspase-1 precursor (pro-Caspase-1) and active fragments (cleaved-Caspase-1), B lymphocytoma-2 protein (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3 precursor (pro-Caspase-3) and active fragments (cleaved-Caspase-3). Results:The intensity of ROS fluorescence and MDA concentration were 120 020±3 245, (4.92±0.09) nmol/mg in the high-glucose group, which were both significantly higher than 35 426±811 and (1.78±0.03) nmol/mg in the normal control group, and the SOD activity was (35.65±1.22) μmol/(min·mg) in the high-glucose group, which was significantly lower than (74.96±1.41) μmol/(min·mg) in the normal control group, showing statistically significant differences between the two groups ( t=35.760, 46.960, 29.830; all at P<0.05). The proliferation rate of RPE cells in high-glucose group was significantly lower than that in normal control group, and the difference was statistically significant ( t=18.820, P<0.05). With the increase of CY-09 concentration, the proliferation rate of cells in the high-glucose group was gradually increased.The proliferation rates of cells treated with 10, 15 and 20 μmol/L CY-09 were all significantly higher than those treated with 0 μmol/L CY-09, showing statistically significant differences between them (all at P<0.05). The proliferation rates of cells treated with 15 μmol/L and 0 μmol/L CY-09 were not significantly different in the normal control group ( P>0.05). The apoptosis rate of cells in the high-glucose group was (21.68±0.41)%, which was significantly higher than (6.67±1.05)% in the normal control group and (13.96±0.07)% in the high-glucose+ CY-09 group, and the differences were statistically significant (both at P<0.05). The relative expression levels of NLRP3, ASC, cleaved-Caspase-1, cleaved-Caspase-3 and Bax proteins were significantly higher and the relative expression levels of Bcl-2 protein was significantly lower in the high-glucose group compared with the normal control group, and the differences were statistically significant (all at P<0.05). The relative expression levels of NLRP3, ASC, the active fragment of cleaved-Caspase-1, Bax and cleaved-Caspase-3 proteins were decreased and the relative expression levels of Bcl-2 protein were increased in the normal+ CY-09 group and high glucose+ CY-09 group compared with the normal control group and high glucose group, and the differences were statistically significant (all at P<0.05). Conclusions:NLRP3 inflammasome mediates the high glucose induced RPE cells apoptosis through ROS/NLRP3/Caspase-1 signaling pathway.

Objective: To investigate the changes of perioperative immune index in patients with breast cancer and its clinical significance. Methods: Th1 cells, Th2 cells, Th1/Th2 ratio and regulatory T cells (Treg) were detected in peripheral blood of 103 patients with primary breast cancer and 116 patients with breast fibroma before surgery and on the 1st, 3rd and 5th day following operation. The relationship of changes in T lymphocyte subsets and clinicopathological characteristics, as well as tumor-free survival of breast cancer patients, was analyzed. Results: The levels of Th1 cells in breast cancer group on the 1st, 3rd and 5th day following operation were (12.20±0.45)%, (13.89±0.47)%, (14.04±0.49)%, which were significantly lower than those before operation [(15.82 + 0.51)%, all P<0.05 ]. Treg cells, however, with the number of (3.82±0.13)%, (3.25±0.11)%, (2.95 ±0.11)%, were remarkably higher than those before operation [(2.53 ±0.11)%, all P<0.05]. With respect to breast fibroma patients, there was no significant difference compared with those before operation of Th1 cells, Th2 cells and Treg cells (all P>0.05). The changes of Th1 cells were associated with the degree of differentiation, T stage, N stage, TNM stage, HER-2 status and Ki-67 (all P<0.05). Treg cells were related to T stage, N stage and HER-2 status (all P<0.05). Tumor-free survival in the Th1-cell-increasing group was significantly better than that in the Th1-cell-decreasing group (P=0.045), while cell-decreasing group of Treg showed the improved outcomes (P=0.012). Conclusions The levels of Th1 cells and Treg cells are important indicators of cellular immune function in patients with breast cancer. Moreover, the perioperative changes of Th1 cells and Treg cells are associated with the size of tumors, pathological parameters, clinical stages and tumor-free survival outcomes.

Objective:To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer (NSCLC) and their effects on prognosis. Methods: A total of 401patients, who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 toAugust 2018, were enrolled as study subjects; and the patients were immunohistochemically tested for PD-L1 and Ki-67. The clinical and pathological data were collected, and the follow-up was performed regularly. The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed. Results: Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9% (152/401) and 96.3% (386/401), respectively. Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression (OR=0.33, 95%CI=0.28-0.39, P<0.0001); Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1; threshold effect analysis, segmentation multivariate logistic and ROC curve analysis showed 14% is a relatively suitable threshold for Ki-67 to be combined with PD-L1. Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group ([21.88±11.25] vs [41.22±16.25]m, P< 0.0001), patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group ([24.75±14.59] vs [38.27± 16.75]m, P<0.0001)], and patients in Ki-67 high/PD-L1 positive group had the shortest DFS as compared to the other three groups ([20.57±11.33] vs [24.11±10.79], [36.00±16.79], [42.91±15.77]m, P<0.0001).As for post-chemotherapy PFS, patients in Ki-67 high expression group was significantly longer than those in Ki-67 low expression group [(7.70±3.01) vs (5.80±2.99)m, P=0.016), but there was no significant difference between PD-L1 positive group and PD-L1 negative group [(7.04±3.21) vs (6.33±3.06)m, P=0.22); for combined evaluation with Ki-67 and PD-L1, the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups [(7.74±3.25) vs (7.43±2.38) vs (4.91±1.97) vs (6.02±3.19)m, P=0.041). Conclusion: Ki-67 is positively correlated with PD-L1 in NSCLC patients, and Ki-67 14% is a suitable threshold for combined use with PD-L1. Both Ki-67 and PD-L1 are predictors of poor prognosis. The combination of the two has an "additive effect" on the prediction of poor prognosis, and patients with high Ki-67 expression are more sensitive to chemotherapy.

Objective To investigate the effects of ulinastatin on renal expression of endothelin￣1 and nitric oxide (NO) in rats with toxic acute kidney injury(AKI). Methods Twenty￣four male SD rats were randomly divided into the normal control group,model control group and treatment groups, with 8 rats in each group. Except normal control group, rats were subcutaneously injected with gentamicin (300 mg.kg-1 .d-1 ) for 3 days to establish a model of toxic AKI.Rats in the treatment group were intraperitoneally injected with a 7￣day course of ulinastatin (30 000 U.kg-1 .d-1 ) from the fourth day.While the other two groups were injected with 0.9% sodium chloride injection (3 mL.kg-1 .d-1 ). The serum level of creatinine and cystatin￣C,urinary concentration of kidney injury molecule￣1(Kim￣1) and neutrophil gelatinase￣associated lipocalin (NGAL), level of endothelin￣1 and NO,expression of endothelin￣1 mRNA,endothelial nitric oxide synthase (eNOS),induced nitric oxide synthase (iNOS),eNOS mRNA and iNOS mRNA in homogenate of renal tissues in each group were detected on the eleventh day. Results Compared with the normal control group,serum level of creatinine and Cystatin￣C,urinary concentration of Kim￣1 and NGAL,level of endothelin￣1 and NO,expression of endothelin￣1 mRNA,iNOS and iNOS mRNA in homogenate of renal tissues were higher in model control group (P<0.01, respectively), while which were lower in treatment group than those in model control group ( P < 0. 01, respectively). And no statistical significant difference of eNOS and eNOS mRNA expression in homogenate of renal tissues existed among the three groups. Conclusion Ulinastatin possesses curative role against rat with toxic AKI via down￣regulating renal expression of endothelin￣1,NO and iNOS.

Clinical records of a patient with olfactory neuroblastoma presented with hyponatremia as initial symptoms were analyzed and the literatures were reviewed. At initial onset, the patient presented with hyponatremia. After pathological examination, the diagnosis was olfactory neuroblastoma. The blood sodium has been normal after operation and radiotherapy. The incidence rate of olfactory neuroblastoma is low, and it is easily misdiagnosed. Its diagnosis relies on pathological examination. We should pay more attention to the unspecific symptoms of patients with hyponatremia, which can help to improve early diagnosis and the prognosis.
Esthesioneuroblastoma, Olfactory ; complications ; pathology ; Humans ; Hyponatremia ; etiology ; Nasal Cavity ; pathology ; Nose Neoplasms ; complications ; pathology ; Prognosis

Objective To evaluate the hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma.Methods Forty-four male patients and 18 female patients were included in this study.They were all with metastatic renal cell carcinoma and received sunitinib treatment at the dose of 50 mg daily in repeated 6 weeks cycle (4 weeks on and 2 weeks off).Toxicity was assessed every cycle with tumor assessments every 2 cycles via CT or PET-CT.Results Fifty patients (80.6％) had experienced treatment-related hematotoxicity,including leucocytopenia,anemia and thrombocytopenia.Severe hematological adverse events ( grade 3 -4 ) occured in 18 patients ( 29.0％ ) and slight events ( grade 1 - 2 ) in others (51.6％).Most of the hematological adverse events were manageable and reversible and treatment-changes (dose reduction,interruption) were necessary in severe cases.Almost half of the dose reduction (9/21,42.9％ ) were owing to hematotoxicity.Conclusions Sunitinib of 50 mg dose on schedule 4/2 is effective and well-tolerated in advanced renal carcinoma patients.Hematological adverse events are frequent in Chinese patients and can be controlled well.

Objective To investigate the effects of Tanshinone Ⅱ A (extracted from Chinese herb medicine Salvia miltiorrhiza Bge.) on ventricular arrhythmias of rabbit hearts induced by ischemia in order to illuminate its mechanism of anti-arrhythmia.Methods Thirty rabbits were randomly (random number)divided into normal group,ischemic group and Tanshinone Ⅱ A group.Model of wedge shaped mass of rabbit left ventricular myocardium with coronary perfusion was prepared,and then by using floating glassy microelectrode,the trans-mural ECG,QT interval,the trans-mural dispersion of re-polarization (TDR) and trans-membrane action potentials from both endocardium and epicardium were simultaneously and wholly recorded.The incidence of ventricular arrhythmia in myocardium was observed after ischemia for thirty min.Results Under the condition of acute ischemia,compared with normal group,the incidence of ventricular arrhythmia and TDR were significantly increased in ischemia group (P ＜ 0.01),while incidence of ventricular arrhythmia and TDR were significantly reduced in tanshinone ⅡA group compared with ischemia group (P ＜ 0.05).The incidences of ventricular arrhythmia in normal,ischemia and Tanshinone Ⅱ A groups were 0/10,9/10 and 2/10 respectively.Conclusions Tanshinone Ⅱ A prevents ventricular arrhythmia and reduces TDR significantly in ischemic rabbit hearts.

ObjectiveTo investigate correlation between drug-resistance related genes and mobile genetic elements of Klebsiella pneumoniae resistant to β-lactams. Methods Forty-seven strains of multidrug-resistant Klebsiella pneumoniae were collected from 6 hospitals in Hangzhou and Huzhou of Zhejiang province from August 2008 to May 2010.Modified Hodge test was performed to detect phenotypes of carbapenemases.Forty kinds of β-lactamases (class A-D),ompK35,ompK36,and 12 kinds of mobile genetic elements were detected by PCR,and the results were analyzed by index cluster.ResultsThirty-five strains were positive in modified Hodge test,and 5 kinds of β-lactamases gene ( including KPC-2-like,GenBank:HQ258934) and 9 kinds of mobile genetic elements were detected.Mutations were observed in ompK35 and ompK36 when compared with sensitive strains.Index cluster analysis showed that correlation existed between KPC-2,KPC-2-like and ISKpn6,between TEM-1 and ISEcpl,IS26,int Ⅰ 1,trbC,IS903,and between CMY-2,OXA-30,DHA-1 and tnpU,tnp513,trbC.ConclusionsFive kinds of β-1actamases genes,and mutations in ompK35 and ompK36 may be associated with the resistance to β-1actams in multidrug-resistant Klebsiella pneumoniae.