Pathological complete response to neoadjuvant therapy with serplulimab and chemotherapy in stage IIIB small cell lung cancer: a case report and literature review

Chemotherapy combined with immunotherapy has significantly improved survival in patients with extensive-stage small cell lung cancer (ES-SCLC), and neoadjuvant immunotherapy combined with chemotherapy has emerged as the standard treatment for those with resectable non-small cell lung cancer (NSCLC). However, the potential benefits of surgery following neoadjuvant immunotherapy combined with chemotherapy in locally advanced SCLC remain unclear. Herein, we report a patient diagnosed with stage IIIB SCLC, who was administered five cycles of neoadjuvant serplulimab combined with chemotherapy followed by surgery, and subsequently achieved a pathologic complete response (pCR). Within a follow-up duration of six months, the patient displayed neither recurrence nor metastasis and experienced no treatment-related adverse reactions of any grade. Based on this case, for locally advanced SCLC, neoadjuvant serplulimab combined with chemotherapy followed by surgery may present an effective, safe, and potentially curative treatment strategy. Nonetheless, further prospective studies are needed to verify our findings

An interferon regulatory factor-like binding element restricts Xmyf-5 expression in the posterior somites during Xenopus myogenesis

AbstractThe expression of myf-5, a key component of myogenic regulatory genes, declines progressively in mature somitic cells during vertebrate myogenesis. Little is known about how this down-regulation takes place. Here we provide evidence that an interferon regulatory factor binding element (IRF element) within the Xenopus myf-5 promoter is responsible for the elimination of myf-5 transcription in mature somitic mesoderm of Xenopus embryos. We show that this IRF element mediates the down-regulation of Xmyf-5 transcription in gastrula embryos, and can specifically interact with nuclear proteins of early neurula. Moreover, deletion of this IRF element results in the anterior expansion of reporter gene transcripts within somitic mesoderm in transgenic embryos. Our results, therefore, provide insight into how the negative control of Xmyf-5 expression takes place

Comparative Proteomics Study on Human High-metastatic Large Cell Lung Cancer Cell Lines Before and After Transfecting with nm23-H1 Gene

Background and objective As a tumor metastasis suppressor gene, the functions of nm23-H1 gene are still unclear. The aim of this study is to better understand the mechanism of lung cancer metastasis and to find new biomarkers for early diagnosis and new target for therapy by conducting comparative proteomics between the human high-metastatic large cell lung cancer cell lines (L9981) and L9981-nm23-H1 (constructed with transfecting nm23-H1 gene into the L9981 cell line). Methods The total proteins of L9981 and L9981-nm23-H1 were separated by immobilized pH gradient (IPG)-based 2-dimensional electrophoresis (2-DE); the significantly differently expressed proteins were examined by mass spectrometry and analyzed by bioinformatics. Results It was observed that nm23-H1 gene transfection caused remarkable changes of the proteome of L9981 compared with L9981-nm23-H1 cells: 5 proteins were deleted, 9 proteins appeared, 16 proteins downregulated, and 12 proteins up-regulated. These proteins are involved in cell framework, signal transduction, metabolism, proliferation and metastasis. Conclusion After nm23-H1 gene is transfected into L9981, proteome in L9981 is remarkably changed. These changes of the proteome could serve as a basis for reversing the invasive and metastatic phenotype in lung cancer and elucidating the machanisms of the metastasis of lung cancer

Interference of Homologous Sequences on the SNP Study of CYP2A13 Gene

Background and objective It has been proven that cytochrome P450 enzyme 2A13 (CYP2A13) played an important role in the association between single nucleotide polymorphisms (SNP) and human diseases. Cytochrome P450 enzymes are a group of isoenzymes, whose sequence homology may interfere with the study for SNP. The aim of this study is to explore the interference on the SNP study of CYP2A13 caused by homologous sequences. Methods Taqman probe was applied to detect distribution of rs8192789 sites in 573 subjects, and BLAST method was used to analyze the amplified sequences. Partial sequences of CYP2A13 were emplified by PCR from 60 cases. The emplified sequences were TA cloned and sequenced. Results For rs8192789 loci in 573 cases, only 3 cases were TT, while the rest were CT heterozygotes, which was caused by homologous sequences. There are a large number of overlapping peaks in identical sequences of 60 cases, and the SNP of 101 amino acid site reported in the SNP database is not found. The cloned sequences are 247 bp, 235 bp fragments. Conclusion The homologous sequences may interfere the study for SNP of CYP2A13, and some SNP may not exist

Magnetically-targetable outer-membrane vesicles for sonodynamic eradication of antibiotic-tolerant bacteria in bacterial meningitis

Treatment of acute bacterial meningitis is difficult due to the impermeability of the blood-brain barrier, greatly limiting the antibiotic concentrations that can be achieved in the brain. Escherichia coli grown in presence of iron-oxide magnetic nanoparticles secrete large amounts of magnetic outer-membrane vesicles (OMVs) in order to remove excess Fe from their cytoplasm. OMVs are fully biomimetic nanocarriers, but can be inflammatory. Here, non-inflammatory magnetic OMVs were prepared from an E. coli strain in which the synthesis of inflammatory lipid A acyltransferase was inhibited using CRISPR/Cas9 mediated gene knockout. OMVs were loaded with ceftriaxone (CRO) and meso-tetra-(4-carboxyphenyl)porphine (TCPP) and magnetically driven across the blood-brain barrier for sonodynamic treatment of bacterial meningitis. ROS-generation upon ultrasound application of CRO- and TCPP-loaded OMVs yielded similar ROS-generation as by TCPP in solution. In vitro, ROS-generation by CRO- and TCPP-loaded OMVs upon ultrasound application operated synergistically with CRO to kill a hard-to-kill, CRO-tolerant E. coli strain. In a mouse model of CRO-tolerant E. coli meningitis, CRO- and TCPP-loaded OMVs improved survival rates and clinical behavioral scores of infected mice after magnetic targeting and ultrasound application. Recurrence did not occur for at least two weeks after arresting treatment.</p

Effect of Kangfuxin

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P=0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P<0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P<0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P<0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application

Synapsis and Meiotic Recombination in Male Chinese Muntjac (Muntiacus reevesi)

The muntjacs (Muntiacus, Cervidae) have been extensively studied in terms of chromosomal and karyotypic evolution. However, little is known about their meiotic chromosomes particularly the recombination patterns of homologous chromosomes. We used immunostained surface spreads to visualise synaptonemal complexes (SCs), recombination foci and kinetochores with antibodies against marker proteins. As in other mammals pachytene was the longest stage of meiotic prophase. 39.4% of XY bivalents lacked MLH1 foci compared to less than 0.5% of autosomes. The average number of MLH1 foci per pachytene cell in M. reevesi was 29.8. The distribution of MLH1 foci differed from other mammals. On SCs with one focus, the distribution was more even in M. reevesi than in other mammals; for SCs that have two or more MLH1 foci, usually there was a larger peak in the sub-centromere region than other regions on SC in M. reevesi. Additionally, there was a lower level of interference between foci in M. reevesi than in mouse or human. These observations may suggest that the regulation of homologous recombination in M. reevesi is slightly different from other mammals and will improve our understanding of the regulation of meiotic recombination, with respect to recombination frequency and position