Through searching and evaluating the evidence on advanced prostate cancer, we found that different types of androgen deprivation had similar effect, and immediate androgen deprivation had survival benefit. For the patient with hormone-refractory prostate cancer, therapies including mitoxantrone, prednisone, docetaxel and surmine were more effective. Strontium-89 provided more effective pain relief than external beam radiation. And bisphophonate had no effect. Antiandrogen withdrawal suggested prostate specific antigen would decline, but the clinical outcome wasn’t reported.
ObjectiveTo investigate the clinical settings, antibiotic susceptibilities, management and outcomes of streptococcal endophthalmitis. MethodsA retrospective observational case series study. Fifty six eyes of 56 patients diagnosed with streptococcal endophthalmitis in Eye & ENT Hospital, Fudan University from 2012 to 2022 were collected. The treatment followed the general principles of relevant guidelines, including pars plana vitrectomy (PPV), vitreous injection of antibiotics (IVI), vitreous injection of glucocorticoids and systemic application of antibiotics. The follow-up time was (11.9±17.0) months. Patients' clinical characteristics, pathogenic distribution and antibiotic susceptibilities, treatment and outcomes in their medical records were retrospectively collected and analyzed. ResultsAll 56 patients had monocular onset, including 39 (69.6%, 39/56) males and 17 (30.4%, 17/56) females, 26 (46.4%, 26/56) with left eyes involved and 30 (53.6%, 30/56) with right eyes involved. Their average age was (25.0±24.4) years. Ocular trauma was the leading cause of streptococcal endophthalmitis (73.2%, 41/56), followed by ophthalmic surgery (23.2%, 13/56) and endogenous infection (3.6%, 2/56). The streptococcal species included Streptococcus viridans (50.0%, 28/56), Streptococcus pneumoniae (18/56, 32.1%) and β-hemolytic Streptococcus (17.9%, 10/56). The susceptibility rates of Streptococcus to penicillin, cefatriaxone, vancomycin and levofloxacin were 66.0%, 57.1%, 94.1% and 92.4%, respectively. Patients received PPV+IVI and IVI as initial treatment were 49 eyes (87.5%, 49/56) and 7 eyes (12.5%, 7/56), respectively. Vitreous injection of glucocorticoids were performed in 17 eyes (30.4%, 17/56); and systemic antibiotics were applied in 52 cases (92.9%, 52/56). At the final follow-up, 47 eyes were recorded with visual acuity. Twenty (35.7%, 20/56) had best corrected visual acuity (BCVA)≥0.05 and 27 (48.2%, 27/56) had BCVA ＜0.05, of which 1 (1.8%, 1/56) had an eyeball enucleation. The etiology of endophthalmitis, streptococcal species, initial treatment with PPV, vitreous injection of glucocorticoids, and systemic antibiotics did not significantly affect patients' visual outcomes (P＞0.05). Timely visit to the hospital after the onset of symptoms (≤3 days) was significantly associated with achieving a final BCVA above 0.05 (P=0.025). ConclusionsOcular trauma was the primary cause of streptococcal endophthalmitis. Streptococcus viridans is the most common pathogenic bacterium. Streptococci had high susceptibility to vancomycin, but patients' visual outcomes were poor.
Survival data were widely used in oncology clinical trials. The methods used, such as the log-rank test and Cox regression model, should meet the assumption of proportional hazards. However, the survival data with non-proportional hazard (NPH) are also quite usual, which will decrease the power of these methods and conceal the true treatment effect. Therefore, during the trial design, we need to test the proportional hazard assumption and plan different analysis methods for different testing results. This paper introduces some methods that are widely used for proportional hazard testing, and summarizes the application condition, advantages and disadvantages of analysis methods for non-proportional hazard survival data. When the non-proportional hazard occurs, we need to choose the suitable method case by case and to be cautious in the interpretation of the results.
Cryptococcosis, mainly caused by Cryptococcus neoformans/gattii species complexes, is a lethal infection in both immunosuppressive and immunocompetent populations. With the upgrade of detection methods and the increase of clinical knowledge, the incidence rate of cryptococcosis is increasing, and it has become one of the most important fungi threatening human health. In recent years, great progress has been made in this field, including the taxonomy and nomenclature of Cryptococcus spp., laboratory diagnostic methods and antifungal susceptibility tests, as well as the characteristics and treatments of cryptococcosis. This article reviews the above contents, in order to improve the clinical and laboratory understanding of the Cryptococcus spp., and realize the timely diagnosis and early treatment of cryptococcosis.
ObjectiveTo construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. ResultsA total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.
A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drug-loaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione (GSH). The low critical solution temperature (LCST) of the micelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic (pH 5.0), reductive (GSH 10 mmol/L) and high temperature (42.0℃) conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as-prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.
目的：研究小鼠头颈鳞癌细胞株SCCⅦ体外放射敏感性，并探讨其与细胞周期阻滞的可能关系。方法：利用细胞克隆形成试验及MTT法检测SCCⅦ细胞受X射线照射后细胞存活能力及细胞生长趋势的变化，通过流式细胞学检测X射线照射后细胞周期分布的变化。结果：相同剂量照射后的SCCⅦ细胞存活分数高于Hela细胞（Plt;0.05）；4 Gy照射后的SCCⅦ细胞在96 h内细胞生长速度仍高于Hela细胞（Plt;0.05）；4 Gy照射后SCCⅦ细胞G1期和G2期细胞比例明显升高（Plt;0.05）。结论：SCCⅦ细胞对放射线不敏感性，放射线导致的细胞周期阻滞是SCCⅦ细胞放射抵抗的可能原因之一
ObjectiveTo summarize the clinical application and future application prospects of organoid model in pancreatic cancer. MethodThe domestic and foreign literature related on the application of organoid model in pancreatic cancer was reviewed. ResultsIn recent years, the organoid model of pancreatic cancer was constructed mainly using patient-derived tissues, fine-needle aspiration samples, and human pluripotent stem cells. The biomarkers of pancreatic cancer were screened according to the histological and structural heterogeneities of the primary tumor retained in organoid model, such as microRNA, glypican-1, annexin A6 and protein biomarkers cytokeratin 7 and 20, cell tumor antigen p53, Claudin-4, carbohydrate antigen 19-9, etc.in the extracellular vesicles. The results of organoid model could maintain the original tumor characteristics and the higher correlation between the organoid model drug sensitivity data and the clinical results of pancreatic cancer patients suggested that, the drug sensitivity data of organoid model could be used to avoid ineffective chemotherapy, so as to improve the treatment response rate and reduce the toxicity of chemical drug treatment, and reasonably select individualized treatment plans for pancreatic cancer patients in future. ConclusionsOrganoid model has many research in screening biomarkers of pancreatic cancer, individualized drug screening, and drug sensitivity test. It can simulate the complex pathophysiological characteristics of pancreatic cancer in vitro, and retain the physiological characteristics and gene phenotype of original tumor cells. It is expected to become a new platform for selecting biomarkers of pancreatic cancer, testing drug sensitivity, and formulating individualized treatment methods for pancreatic cancer, which might further accelerate the research progress of pancreatic cancer.
Objective To investigate the pathogen distribution and drug resistance in ICU patients, provide reference for prevention of severe infection and empirical antibacterial treatment. Methods The patients admitted in ICU between January 2013 and December 2014 were retrospectively analyzed. The pathogenic data were collected including bacterial and fungal culture results, the flora distribution and drug resistance of pathogenic bacteria. Results A total of 2088 non-repeated strains were isolated, including 1403 (67.2%) strains of Gram-positive bacteria, 496 (23.8%) strains of Gram-negative bacteria, and 189 (9.0%) strains of fungus. There were 1324 (63.42%) strains isolated from sputum or other respiratory specimens, 487 (23.33%) strains from blood specimens, 277 (13.27%) strains from other specimens. The bacteria included Acinetobacter baumannii (17.2%), Klebsiella pneumoniae (14.8%), Pseudomonas aeruginosa (9.9%), C. albicans (6.3%), E. coli (5.6%), E. cloacae (5.4%), Epidermis staphylococcus (5.0%) and Staphylococcus aureus (4.7%). There were 15 strains of penicillium carbon resistant enterobacteriaceae bacteria (CRE) accounting for 2.3%, including 5 strains of Pneumonia klebsiella, 4 strains of E. cloacae. In 117 strains of E. coli, drug-resistant strains accounted for 86.4% including 85.5% of multiple drug-resistant strains (MDR) and 0.9% of extremely-drug resistant (XDR) strains. In 359 strains of Acinetobacter baumannii, drug-resistant strains accounted for 75.2% including 72.1% of XDR strains and 3.1% of MDR strains. MDR strains accounted for 10.6% in Pseudomonas aeruginosa. Detection rate of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase-negative Staphylococci (MRCNS) was 49.0% and 95.5%, respectively. There were 4 strains of vancomycin resistant Enterococcus faecalis. There were 131 (69.3%) strains of C. albicans, 23 (12.2%) strains of smooth candida. C. albicans was sensitive to amphotericin and 5-fluorine cytosine, and the resistance rate was less than 1% to other antifungle agents. The resistance rate of smooth ball candida was higher than C. albicans and nearly smooth candida, but still less than 15%. Conclusions The predominant pathogens in ICU was gram-negative bacteria. The top eight pathogenic bacteria were Acinetobacter baumanni, Klebsiella pneumoniae, Pseudomonas aeruginosa, C. albicans, E. coli, E. cloacae, Epidermis staphylococcus and S. aureus. Sputum and blood are common specimens. CRE accounts for 2.3%. Drug-resistant strains are most common in E. coli mainly by MDR, followed by Acinetobacter baumannii mainly by XDR, and least in Pseudomonas aeruginosa. C. albicans is the most common fungus with low drug resitance.