Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Diagnostic value and safety of medical thoracoscopy for pleural effusion of different causes.

BACKGROUND: Pleural effusions occur for various reasons, and their diagnosis remains challenging despite the availability of different diagnostic modalities. Medical thoracoscopy (MT) can be used for both diagnostic and therapeutic purposes, especially in patients with undiagnosed pleural effusion. AIM: To assess the diagnostic efficacy and safety of MT in patients with pleural effusion of different causes. METHODS: Between January 1, 2012 and April 30, 2021, patients with pleural effusion underwent MT in the Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Shaanxi, China). According to the discharge diagnosis, patients were divided into malignant pleural effusion (MPE), tuberculous pleural effusion (TBPE), and inflammatory pleural effusion (IPE) groups. General information, and tuberculosis- and effusion-related indices of the three groups were analyzed. The diagnostic yield, diagnostic accuracy, performance under thoracoscopy, and complications of patients were compared among the three groups. Then, the significant predictive factors for diagnosis between the MPE and TBPE groups were analyzed. RESULTS: Of the 106 patients enrolled in this 10-year study, 67 were male and 39 female, with mean age of 57.1 ± 14.184 years. Among the 74 thoracoscopy-confirmed patients, 41 (38.7%) had MPE, 21 had (19.8%) TBPE, and 32 (30.2%) were undiagnosed. Overall diagnostic yield of MT was 69.8% (MPE: 75.9%, TBPE: 48.8%, and IPE: 75.0%, with diagnostic accuracies of 100%, 87.5%, and 75.0%, respectively). Under thoracoscopy, single or multiple pleural nodules were observed in 81.1% and pleural adhesions in 34.0% with pleural effusions. The most common complication was chest pain (41.5%), followed by chest tightness (11.3%) and fever (10.4%). Multivariate logistic regression analyses showed effusion appearance [odds ratio (OR): 0.001, 95%CI: 0.000-0.204; P = 0.010] and carcinoembryonic antigen (OR: 0.243, 95%CI: 0.081-0.728; P = 0.011) as significant for differentiating MPE and TBPE, with area under the receiver operating characteristic curve of 0.977 (95%CI: 0.953-1.000; P < 0.001). CONCLUSION: MT is an effective, safe, and minimally invasive procedure with high diagnostic yield for pleural effusion of different causes.

Delisheng Injection (), a Chinese medicinal compound, enhanced the effect of cis-platinum on lung carcinoma cell line PGCL3.

OBJECTIVE: To investigate the effect of Delisheng Injection (, DLS), a Chinese medicinal compound, DLS combined with cis-platinum (DDP), an active agent used in lung cancer chemotherapy, on a human highly metastatic giant lung carcinoma cell line PGCL3. METHODS: The suspended PGCL3 cells at 10(5) /mL cultured in 96-well tissue culture plates were divided into 4 groups: DLS treatment group (2 µL/mL, 5 µL/mL, 10 µL/mL, 25 µL/mL), DDP treatment group (1 µg/mL, 2 µg/mL, 5 µg/mL, 15 µg/mL), combined DLS with DDP treatment group (DLS:DDP 2 µL/mL:1 µg/mL, 5 µL/mL:2 µg/mL, 10 µL/mL:5 µg/mL, 25 µL/mL:15 µg/mL) and a control group. The cytotoxicity of DLS with different concentrations (2 µL/mL, 5 µL/mL, 10 µL/mL, 25 µL/mL) on PGCL3 cells was determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. Effect of DLS on adhesion of PGCL-3 cells was tested by cell-matrigel adhesion assay. Chemotactic movement model of transwell camerula was used to determine the effect of DLS on invasion and migration of PGCL-3 cells. RESULTS: Compared with the control group, DLS (2 µL/mL, 5 µL/mL, 10 µL/mL, 25 µL/mL) could significantly decrease cell proliferation, adhesion, invasion and migration abilities (P <0.05). Cell adhesion, invasion and migration abilities were significantly decreased after combination treatment of DLS:DDP (2 µL/mL:1 µg/mL, 5 µL/mL:2 µg/mL, 10 µL/mL:5 µg/mL, 25 µL/mL:15 µg/mL) compared with DDP single-agent treatment (1 µg/mL, 2 µg/mL, 5 µg/mL, 15 µg/mL, P<0.05), respectively. CONCLUSIONS: DLS single-agent has a satisfying inhibition effect in PGCL3 cell line and DLS might enhance the inhibition effect of DDP on cancer metastasis. Our research provided a experimental basis about the treatment on highly metastatic lung caner.

Effects of neurotrophins on gastrointestinal myoelectric activities of rats.

AIM: To observe the effects of mouse nerve growth factor (NGF), rat recombinant brain derived neurotrophic factor (rm-BDNF) and recombinant human neurotrophin-3 (rh-NT-3) on the gastrointestinal motility and the migrating myoelectric complex (MMC) in rat. METHODS: A randomized, double-blinded, placebo-controlled experiment was performed. 5-7 days after we chronically implanted four or five bipolar silver electrodes on the stomach, duodenum, jejunum and colon, 21 experimental rats were coded and divided into 3 groups and injected NGF, rm-BDNF, rh-NT-3 or placebo respectively via tail vein at a dose of 20 microg x kg(-1). The gastrointestinal myoelectrical activity was recorded 2 hours before and after the test substance infusions in these consciously fasting rats. RESULTS: The neurotrophins-induced pattern of activity was characterized by enhanced spiking activity of different amplitudes at all recording sites, especially in the colon. In the gastric antrum and intestine, only rh-NT-3 had increased effects on the demographic characteristics of electrical activities (P<0.05), but did not affect the intervals of MMCs. In the colon, all the three kinds of neurotrophins could significantly increase the frequency, amplitude and duration levels of spike bursts, and also rh-NT-3 could prolong the intervals of MMC in the transverse colon (25+/-11 min vs 19+/-6 min, P<0.05). In the distal colon rh-NT-3 could evoke phase III-like activity and disrupt the MMC pattern, which was replaced by a continuously long spike bursts (LSB) and irregular spike activity (ISA) for 48+/-6 min. CONCLUSION: Exogenous neurotrophic factors can stimulate gut myoelectric activities in rats.