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.
ObjectiveTo summarize current patient-derived organoids as preclinical cancer models, and its potential clinical application prospects. MethodsCurrent patient-derived organoids as preclinical cancer models were reviewed according to the results searched from PubMed database. In addition, how cancer-derived human tumor organoids of pancreatic cancer could facilitate the precision cancer medicine were discussed. ResultsThe cancer-derived human tumor organoids show great promise as a tool for precision medicine of pancreatic cancer, with potential applications for oncogene modeling, gene discovery and chemosensitivity studies. ConclusionThe cancer-derived human tumor organoids can be used as a tool for precision medicine of pancreatic cancer.
Antimicrobial resistance is a rigorous health issue around the world. Because of the short turn-around-time and broad pathogen spectrum, culture-independent metagenomic next-generation sequencing (mNGS) is a powerful and highly efficient tool for clinical pathogen detection. The increasing question is whether mNGS is practical in the prediction of antimicrobial susceptibility. This review summarizes the current mNGS-based antimicrobial susceptibility testing technologies. The critical determinants of mNGS-based antibacterial resistance prediction have been comprehensively analyzed, including antimicrobial resistance databases, sequence alignment tools, detection tools for genomic antimicrobial resistance determinants, as well as resistance prediction models. The clinical challenges for mNGS-based antibacterial resistance prediction have also been reviewed and discussed.
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.
Objective To evaluate the utility of collagen-gel droplet embedded-culture drug sensitivity test (CD-DST) in pancreatic carcinoma cell by compared with WST-8. Methods The chemosensitivity to 5-fluorouracil (5-FU), gemzar (GEM) and oxaliplatin (OXA) of pancreatic adenocarcinoma cells SW1990, PCT-3 and ASPC-1 were tested by WST-8 and CD-DST respectively. Results In a certain living cell number range (500-10 000), there was a linear correlation (r=0.991 1, P＜0.05) between the integral optical density in CD-DST and the cell number. The inhibition ratios of three kinds of cell growth tested by CD-DST were higher than those tested by WST-8 (P＜0.05). The results of drug chemosensitivity to 5-FU， GEM and OXA detected by two methods were uniform. Conclusion The CD-DST can be used to assay the drug chemosensitivity in vitro for pancreatic carcinoma.
ObjectiveTo evaluate the efficacy and cost-effectiveness of thymalfasin (Tα1) as an adjuvant therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery.MethodsPatients with HBV-related HCC who underwent hepatectomy from February 2007 to December 2015 in West China Hospital of Sichuan University, Chengdu Military General Hospital, or the Third Affiliated Hospital of Sun Yat-sen University were retrospectively collected and divided into the Tα1 group and the observation group. Log-rank test and Kaplan-Meier curve were used to assess the overall survival, recurrence-free survival, and safety of patients. A Markov model was used to calculate the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of the Tα1 group compared with the observation group. Cost data was from the hospital information system of the three hospitals. Utility scores mainly came from published data. Sensitivity analyses were applied to explore the impact of essential variables.ResultsA total of 208 patients with HCC after liver resection were enrolled, among them 48 received Tα1 treatment (the Tα1 group) and 160 were only followed up (the observation group). There was no significant difference between the two groups in the baseline characteristics. The median overall survival of the Tα1 group and the observation group was 102.0 months [95% confidence interval (CI) (74.8, 129.2) months] and 81.6 months [95%CI (65.7, 97.6) months], respectively, and the difference was statisitically significant (P=0.047); the median recurrence-free survival was 66.7 months [95%CI (17.3, 116.1) months] and 37.4 months [95%CI (28.7, 46.2) months], respectively, and the difference was statistically significant (P=0.044). There were no grade Ⅲ-Ⅳ adverse events and no treatment-related death occurred. The ICER of Tα1 group was ￥108 050.02/QALY, which was less than the willingness to pay (￥177 785.25/QALY).ConclusionsTα1, as an adjuvant therapy for HBV-related HCC patients, can improve the prognosis of the patients, and the cost is within the acceptable level in our country, so this strategy is likely to be a cost-effective option compared with the observation group.
Objective To explore the effect of hydrostatic pressure on intracellular free calcium concentration ([Ca2+]i) and the gene expression of transient receptor potential vanilloid (TRPV) in cultured human bladder smooth muscle cells (hb-SMCs), and to prel iminarily probe into the possible molecular mechanism of hb-SMCs prol iferation stimulated by hydrostatic pressure. Methods The passage 6-7 hb-SMCs were loaded with Ca2+ indicator Fluo-3/AM. When the hb-SMCs were under 0 cm H2O (1 cm H2O=0.098 kPa) (group A) or 200 cm H2O hydrostatic pressure for 30 minutes (group B) and then removing the 200 cm H2O hydrostatic pressure (group C), the [Ca2+]i was measured respectively by inverted laser anningconfocal microscope. When the hb-SMCs were given the 200 cm H2O hydrostatic pressure for 0 hour, 2 hours, 6 hours, 2 hours, and 24 hours, the mRNA expressions of TRPV1, TRPV2, and TRPV4 were detected by RT-PCR technique. Results The [Ca2+]i of group A, group B, and group C were (100.808 ± 1.724), (122.008 ± 1.575), and (99.918 ± 0.887) U, respectively; group B was significantly higher than groups A and C (P lt; 0.001). The [Ca2+]i of group C decreased to the base l ine level of group A after removing the pressure (t=0.919, P=0.394). The TRPV1, TRPV2, and TRPV4 genes expressed in hb-SMCs under 200 cm H2O hydrostatic pressure at 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, but the expressions had no obvious changes with time. There was no significant difference in the expressions of TRPV1, TRPV2, and TRPV4 among 3 groups (P gt; 0.05). Conclusion The [Ca2+]i of hb-SMCs increases significantly under high hydrostatic pressure. As possible genes in stretch-activated cation channel, the TRPV1, TRPV2, and TRPV4 express in hb-SMCs under 200 cm H2O hydrostatic pressure. It is possible that the mechanical pressure regulates the [Ca2+]i of hb-SMCs by opening the stretch-activated cation channel rather than up-regulating its expression.
【 Abstract 】 Objective To observe the effect of disruption of hypoxia inducible factor-1 α (HIF-1 α ) pathway by small hairpin RNA (shRNA) on chemosensitivity of human hepatocellular carcinoma (HCC) cells and to reveal the correlative mechanisms. Methods Plasmid of pshRNA-HIF-1α was transfected into HepG2 cells by lipofectamine. HepG2/pshRNA-HIF-1α (HepG2/pshRNA) cell lines were obtained by selection of HepG2 cells in G418. Meanwhile, plasmid of empty vector (pHK) was transfected as a control (HepG2/pHK). The mRNA and protein expression levels of HIF-1α and mdr1 were investigated by RT-PCR and Western blot respectively. Using CoCl2 to simulate the hypoxia condition, growth inhibition and apoptosis rates of HepG2 cells under different dosages of chemotherapeutic agents (adriamycin) were measured by MTT assay and flow cytometry (FCM) ． ResultsCompared with HepG2/pHK cells, the mRNA and protein expression levels of HIF-1αand mdr1 were obviously down-regulated in HepG2/pshRNA cells. At the same time, the proliferation inhibition and apoptosis rates were evidently increased after transfection with pshRNA-HIF-1α(P＜0.05)，which decreased the expression of HIF-1αto 82.18% at mRNA level and 75.51% at protein level. There was no significant effect of transfection pHK (Pgt;0.05). Conclusion These data demonstrates that HIF-1α interference by shRNA increased the sensitivity of HCC chemotherapy and the reversal of multidrug resistance, which may be done by down-regulating the transcription of mdr1 and the translation of P-gp. Blocking HIF-1αin HCC cells may offer an new avenue for gene therapy．
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
Objective To investigate the correlation between OPRM1 A118G gene polymorphism and Eysenck personality type and pain sensitivity. Methods The surgical patients who were transferred from Department of Emergency Medicine to Department of General Surgery of Luzhou People’s Hospital between January 2018 and December 2020 were selected. Before surgery, Eysenck Personality Questionnai (EPQ) was used to investigate the patient’s personality type, and the pain threshold and pain tolerance threshold were determined by electric stimulation instrument. The OPRM1 A118G genotype of peripheral venous blood was detected by polymerase chain reaction-restriction fragment length polymorphism analysis technique. Patients were divided into wild homozygous (A/A) group, mutant heterozygous (A/G) group and mutant homozygous (G/G) group according to the typing results. The general condition, pain sensitivity, EPQ score, difference of Eysenck personality type and correlation between Eysenck personality type and pain sensitivity were analyzed. Results A total of 356 patients were enrolled, including 174 in A/A group, 136 in A/G group and 46 in G/G group. The mutation rate of OPRM1 A118G gene was 32.00%. There were statistically significant differences in pain sensitivity (pain threshold, pain tolerance threshold) and scores of introverted and extraverted, neurotic and dissemble personality types among three groups (P<0.05). There were significant differences in introverted and extraverted and psychotic personality types among the three groups (P<0.05). There were significant differences in pain threshold and pain tolerance threshold among different introverted, extraverted and psychotropic personality types (P<0.05). Conclusion Both OPRM1 A118G gene polymorphism and Eysenck personality type have influence on pain sensitivity, and there is a correlation between them.