Although tumor immunotherapy has been proposed for many years,the consensus denoting it as an essential approach for fighting against cancer is reached only in recent years. Tumor immunotherapy can be categorized as active and passive ones. In order to successfully cure cancer,safe and efficient active immunotherapy is required. Dendritic cells (DCs)are not only the bridge linking innate and adaptive immunity,but also the key determinants of the quality of adaptive immunity:immunity versus immune tolerance. Therefore,the safe and efficient DC-based tumor-specific and broad-spectral tumor vaccine has an irreplaceable important position in tumor immunotherapy. Because of the high heterogeneity of DCs, the research on DC-based tumor vaccine has encountered a bottleneck. Here,we reviewed the progress in research on DC-based tumor vaccine and related problems needed to be resolved with the incorporation of our experiences.

Objective To analyze the long-term results of fractionated stereotactie radiotherapy(FSRT)for the local residual lesion after the first course of radiotherapy for nasopharyngeal carcinoma.Methods From July 1997 to July 2002,46 patients were treated with FSRT.According to the 1992 Fuzhou staging system,the number of patients was 1,6,30 and 9 with stage Ⅰ,Ⅱ,Ⅲ and Ⅳ disease,respectirely;3,11,27 and 5 with T1,T2,T3 and T4 tumor,respectively;14,16,12 and 4 with N0,N1,N2and N3 disease.Radiotherapy was delivered to tumors with the total of dose 68-70 Gy in 7-8w.Chemotherapy(2 cycles of PVF or POF)was given to the patients with stage Ⅲ and Ⅳ a disease.FSRT was given to the residual disease with the total dose of 18-24 Gy in 3 fractions with an interval of 3-7 days.The reference dose line was 70%-90%.Resuits CR and PR rates in this group were 61%and 39%,respectively.The overall survival rates of each year from 1- to 5-year were 100%,87%,83%,78%and 76%.The 1-,3- and 5-year disease-free survival rates were 100%,93%and 89%;The distant metastasis-free survival rates were 100%,85%and 79%;The local-regional control survival rates were 100%,94%and 91%.Seventeen patients who died during the follow-up period were 1 for local cervical lymph node recurrence,2 for fatal nasopharyngeal hemorrhage,4 for local nasopharynx recurrence,and 10 for distance metastases. Conclusions Fraetionated stereotactic radiotherapy is safe and effective for the patients with residual lesion of nasopharyngeal carcinoma at the primary site after radiotherapy.The optimized fractionation and total dose requires the further investigation.

OBJECTIVE　To study the pharmacokinetics of levofloxacin-methane sulfonic acid (LF-MSA)in 8 patients with pulmonary tuberculosis after administration 400 mg orally.METHODS　The concentrations of LF-MSA in serum were measured by HPLC.The pharmacokinetic paramters were obtained using 3P97 program.RESULTS　The results showed that a one-compartment model with 1 st order absorption were fitted for LF-MSA.The average values of tmax was 1.22 h.The concentrations of LF-SA in serum was (4.52±0.72) mg*L-1.The mininal concentrations of LF-AS at 24 hr after a single dose was (0.52±0.26) mg*L-1.The average area under the curve was (48.35±5.38) mg*h*L-1.The elimination half-life was (6.49±1.70) h.The apparent volume of distribution was (77.48±8.33)L.CONCLUSION　According to our study,it was suggested that 400 mg twice daily may be given in order to maintain the concentrations of LF-SA in serum around 24 hours above the minimal concentrations of bactericide.

Objective To investigate the effect of early low-glucocorticoid on hemodynamics and prognosis in the patients with septic shock.Methods Sixty patients with septic shock failing in active fluid resuscitation and vasoactive drugs in our hospital from June 2013 to August 2015 were selected and divided into the control group,early-hormone group and late-hormone group.MAP,HR,PO2/FIO2 and serum lactic acid levels were monitored in all selected patients before treatment and at 12,24,48 h after treatment.Apache Ⅱ,SOFA scores were assessed before treatment and on 1,3,7 d after treatment.The ventilation time,ICU stay time,hospital stay time and intravenous use time of vasoactive agents(VDNT) were recorded.Results The Apache Ⅱ scores and SOFA scores on 3,7 d after treatment in the early-hormone group were significantly decreased compared with the late-hormone group and control group (P＜0.05).MAP and HR at 24,48 h after treatment in the early-hormone group were significantly improved compared with the late-hormone group and control group (P＜0.05).The level of serum lactic acid at 12,24 h after treatment in the early-hormone group and late-hormone group were obviously lower than that in the control group,the levels of serum lactic acid at 12,24 h after treatment in the early-hormone group were obviously lower than those in the late-hormone group (P＜ 0.05).PO2/FIO2 at 12 h after treatment in the early-hormone group and late-hormone group were obviously better than that in the control group,and PO2/FIO2 at 12 h after treatment in the early-hormone group was obviously better than that in the late-hormone group(P＜0.05).The ventilation time,ICU stay time,hospital stay time and VDUT in the early-hormone group were significantly shortened compared with the late-hormone group and control group.The ventilation times,ICU stay time and VDUT in the latehormone group were significantly shortened compared with the control group (P＜0.05).Conclusion Early using low-dose glucocorticoid may restore hemodynamics more quickly,protects the organ function and improves the prognosis in the patients with septic shock.

Objective To explore the subcellular localization of Galectin-9 and its effect on allogeneic immune response.Methods The plasmid pEGFP-N1 was inserted with Galectin-9 fragment which was amplified from pBKCMV-Galectin-9 by PCR.The recombinant plagmid wag then transfected into CHO cells using JetPEI in vitro.The cells were cultured in G418 selecting mediam to obtain the stably-transfected cells.The transcription and expression of Galectin-9 gene were verified by immunohistochemical staining and RT-PCR.The solid-phase transgenic CHO cells or freshly-cultured supernatant wag added into the mixed lymphocyte response system to detect the inhibitory effect of Galectin-9.Galectin-9 protein wag administered intraperitoneally for 7d consecutively.Results The expression of Galectin-9 wag localized in the cytosol of CHO.The allogeneic mix lymphocyte proliferation was dose-dependently inhibited by the freshly-cultured supernatant from stably-transfected CHO cells.Furthermore,the supernatant from stably-transfected CHO cells dose-dependently inhibited the level of IL-2.The inhibitory effect could be reversed by Tim-3-Fc blocking.Administration of Galectin-9 significantly prolonged the survival of allogeneic cardiac transplants[(22.7±1.2)d vs(7.2±0.4)d)].Conclusion Galectin-9 may be secreted in physical situation to exert its immunomodulatory function on allogeneic immune response.Furthermore.Galectin-9 may be a novel therapeutic drug in transplant medicine.

Objective:To investigate the predictive value of KAI1 expression in colon cancer tissues for tumor recurrence.Methods:Ninety-two pathological tissue samples were collected from patients undergoing radical operation for colon cancer in Tangshan People's Hospital from August 2010 to November 2011. According to the results of follow-up, the patients were divided into recurrent group (33 cases) and non-recurrent group (59 cases). KAI1 expression in tumor tissues was detected by immunohistochemistry. χ2 test was used to analyze the relationship between KAI1 expression in colon cancer tissues and clinicopathological characteristics of patients with colon cancer. Spearman correlation test was used to analyze the relationship between KAI1 expression in colon cancer tissues and the recurrence time of patients. Cox proportional hazards model was used to analyze the related factors affecting postoperative recurrence of colon cancer. Results:KAI1 expression in tumor tissues in the recurrent group was lower than that in the non-recurrent group [39.39% (13/33) vs. 62.71% (37/59), χ2 = 4.638, P = 0.031]. KAI1 expression was not associated with patients' gender, age and tumor maximum diameter (all P > 0.05), but related to the tumor differentiation and lymphatic metastasis [high and medium differentiation vs. low differentiation: 70.3% (26/37) vs. 43.6% (24/55), χ2 = 6.324, P =0.012; lymph node metastasis vs. non-lymph node metastasis: 43.2% (19/44) vs. 64.6% (31/48), χ2 = 4.238, P = 0.039]. KAI1 expression in tumor tissues was positively correlated with tumor recurrence time ( r = 0.845, P < 0.05). Cox multivariate analysis showed that the low differentiation of the tumor, lymph node metastasis and negative expression of KAI1 in colon cancer tissues were independent risk factors for recurrence of colon cancer after surgery ( HR = 1.736, 95% CI 1.598-5.391, P = 0.019; HR =1.526, 95% CI 1.175-3.029, P = 0.037; HR = 1.799,95% CI 1.756-5.825, P = 0.013). Conclusion:Low KAI1 expression in colon cancer tissues is closely related to colon cancer recurrence, and the detection of KAI1 expression in colon cancer tissues has certain predictive value for tumor recurrence.

Microplastics(MPs)have attracted growing attention worldwide as an increasingly prevalent environmental pollutant.In addition,chicken meat is currently the most widely consumed kind of poultry in the global market.Consumer demand for chicken is on the rise both at home and abroad.As a result,the safety of chicken raising has also received significant attention.The lungs play an essential role in the physiological activities of chickens,and they are also the most vulnerable organs.Lung injury is difficult to repair after the accumulation of contaminants,and the mortality rate is high,which brings huge economic losses to farmers.The research on the toxicity of MPs has mainly focused on the marine ecosystem,while the mechanisms of toxicity and lung damage in chickens have been poorly studied.Thus,this study explored the effects of exposure to polystyrene microplastics(PS-MPs)at various concentrations for 42 d on chicken lungs.PS-MPs could cause lung pathologies and ultrastructural abnormalities,such as endoplasmic reticulum(ER)swelling,inflammatory cell infiltration,chromatin agglutination,and plasma membrane rupture.Simultaneously,PS-MPs increased the expression of genes related to the heat shock protein family(Hsp60,Hsp70,and Hsp90),ER stress signaling(activating transcription factor 6(ATF6),ATF4,protein kinase RNA-like ER kinase(PERK),and eukaryotic translation initiation factor 2 subunit α(eIF2α)),pyroptosis-related genes(NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),interleukin-1β(IL-1β),cysteinyl aspartate-specific proteinase 1(Caspase1),and gasdermin-D(GSDMD)),and the inflammatory signaling pathway(nuclear factor-κB(NF-κB),inducible nitric oxide synthase(iNOS),and cyclooxygenase-2(COX-2)).The above results showed that PS-MP exposure could result in lung stress,ER stress,pyroptosis,and inflammation in broilers.Our findings provide new scientific clues for further research on the mechanisms of physical health and toxicology regarding MPs.

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.
Aneuploidy ; Cell-Free Nucleic Acids/genetics* ; Consensus ; DNA Copy Number Variations ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Prenatal Diagnosis

Objective:To study the effectiveness and safety of PD-1(programmed cell death protein-1,PD-1)inhibitors for the treatment of patients with advanced cancer in real-world in a Chinese cohort. Methods:Data of patients with advanced cancer who were admitted to the Department of Oncology,Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between May 2018 and September 2019 and received PD-1 inhibitor alone orcombined with otheranti-cancer therapies were collected.The clinical characteristics,therapeutic efficacy and adverse events were analyzed retrospectively. Results:A total of 75 patients with advanced cancer were included in this study.The cohort consisted of 53 males and 22 females with an average age of 60 years,among whom 60 patients had metastasis.Lung cancer(27 cases)and gastric cancer(12 cases)accounted for the largest proportion.Other cancer types included cancers of the digestive system(colorectal,liver,pancreatic,esophageal,and bile duct cancer),urinary system(kidney,pelvis,ureter,and bladder cancer)and female reproductive system(breast,cervical,and ovarian cancer),malignant melanoma,and head and neck cancer(nasopharyngeal and laryngeal cancer).Among all the patients studied,55 patients(73.3％)received PD-1 inhibitors as first-line and(or)second-line therapy,and 62 patients(82.7％)received PD-1 inhibitors in combination with other anti-cancer therapies.The objective response rate was 1 4.5％,disease control rate was 65.2％,the median progression-free survival was 6.1 months[95％confidence interval(C/):4.356-7.844],and the median overall survival was 1 8.0 months(95％CI:9.565-26.435).Adverse events,mainly grade 1 or grade 2,accured in 5 5 patients.The progression-free survival was 6.3 months in patients treated with PD-1 inhibitors as first-line and(or)second-line therapy,significantly longer than the 3.0-month-long progression-free survival of the patients treated with PD-1 inhibitors as third-line or multiline therapy[hazard ratio(HR)=0.492,95％Cl:0.244-0.992,P=0.048]. Conclusions:Immunotherapy with PD-1 inhibitors was effective and safe for patients with advanced cancer in real-world,especially in those who received PD-1 inhibitor treatment as first-or second-line therapy.

Objective:To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality.Methods:This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results:The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups ( P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×10 9/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases ( OR=0.01, 95% CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) ( OR=3.31, 95% CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) ( OR=1.56, 95% CI 1.05-2.32, P=0.029) and D dimer ( OR=1.49, 95% CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95% CI 0.79-0.94), 0.89 (95% CI 0.84-0.95) and 0.87 (95% CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions:Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.