[Analysis of the efficacy and safety of dual immunotherapy in patients with driver gene and programmed death ligand-1 double negative advanced non-small cell lung cancer].

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

[Exploration of the treatment model for patients with advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease based on real-world data].

Objective: To explore whether combining treatment of chronic obstructive pulmonary disease (COPD) with anti-tumor therapy is better than that of tumor treatment alone in advanced non-small cell lung cancer (NSCLC) patients with COPD in the real world. Methods: The clinical data of 101 patients with advanced NSCLC complicated with COPD from January 1, 2015, to December 31, 2017, in the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively, including 99 males and two females, aged from 52 to 84 years[average (67±8) years]. Among the patients, 90 (89.1%) were smokers, with an average pack-year smoking index of (47±4) . The patients were divided into observation and control groups, depending on whether they received standardized anti-COPD supportive treatment. In the observation group, there were 36 patients, including 35 males and one female, aged from 54 to 84 years[ average (67±8) years], with an average pack-year of smoking (47±4). There were 65 patients in the control group, including 64 males and one female, aged from 52 to 83 years [average (67±8) years], with an average pack-year of smoking 47±4. There was no significant difference in the baseline data between the two groups. The primary outcome measures included the Objective response rate (ORR), disease control rate (DCR), disease-free survival (PFS), and overall survival (OS) of the two groups. An unpaired t-test was used to compare continuous variables between the observation and control groups. The Pearson chi-square test was used to compare categorical variables between the two groups. Kaplan-Meier survival curves were used to evaluate the median PFS and median OS of patients, and the log-rank test was used to assess differences between groups. Result: The ORR of the observation group and the control group was 22.6% (7 cases) and 22.2% (11 cases), respectively, with no significant difference (χ(2)=0.01, P=0.971). The DCR between the observation group and the control group was 58.1% (19 cases) and 57.8% (27 cases), with no significant difference (χ(2)=0.02, P=0.889). Median PFS in the observation group was 6.0 months, which was better than the 3.5 months in the control group (χ(2)=3.947, P<0.05). The median OS of the observation group was 18.0 months, which was better than the 15.0 months of the control group (χ(2)=4.083, P<0.05). Conclusions: Compared with the treatment of tumors alone, combination of anti-tumor therapy with anti-COPD therapy showed longer PFS and OS in patients with advanced NSCLC complicated with COPD.

[Clinical analysis of 36 cases of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4].

Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO(2) improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion: Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.

Ubiquitin D is correlated with colon cancer progression and predicts recurrence for stage II-III disease after curative surgery.

BACKGROUND: Our recent study observed that the expression of ubiquitin D (UBD), a member of ubiquitin-like modifier family, was upregulated in colon cancer parenchymal cells. The present study further investigated the clinical signicance of UBD in colon cancer. METHODS: Using quantitative PCR, tissue microarray (TMA), western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and protein levels in tumour tissues from patients with colon cancer at different stages and in paired adjacent normal epithelium. RESULTS: Immunohistochemical detection of UBD on a TMA containing 203 paired specimens showed that increased cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph node metastasis, distant metastasis, tumour histologic grade, advanced clinical stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a significantly higher disease recurrence rate and poorer survival than patients with UBD-negative tumours after the radical surgery. Stratification analysis according to tumour stage revealed UBD as an independent predictor for tumour recurrence in patients with stage II and III tumours. CONCLUSION: UBD may contribute to the progression of colon carcinogenesis and function as a novel prognostic indicator of forecasting recurrence of stage II and III patients after curative operations.

Fine organization of Bombyx mori fibroin heavy chain gene.

The complete sequence of the Bombyx mori fibroin gene has been determined by means of combining a shotgun sequencing strategy with physical map-based sequencing procedures. It consists of two exons (67 and 15 750 bp, respectively) and one intron (971 bp). The fibroin coding sequence presents a spectacular organization, with a highly repetitive and G-rich (approximately 45%) core flanked by non-repetitive 5' and 3' ends. This repetitive core is composed of alternate arrays of 12 repetitive and 11 amorphous domains. The sequences of the amorphous domains are evolutionarily conserved and the repetitive domains differ from each other in length by a variety of tandem repeats of subdomains of approximately 208 bp which are reminiscent of the repetitive nucleosome organization. A typical composition of a subdomain is a cluster of repetitive units, Ua, followed by a cluster of units, Ub, (with a Ua:Ub ratio of 2:1) flanked by conserved boundary elements at the 3' end. Moreover some repeats are also perfectly conserved at the peptide level indicating that the evolutionary pressure is not identical along the sequence. A tentative model for the constitution and evolution of this unusual gene is discussed.

Identification and characterization of a silkgland-related matrix association region in Bombyx mori.

From DNA fragments in vivo attached to the nuclear matrix in silkglands of Bombyx mori 5th instar larvae, we have screened a matrix association region (MAR), termed BmMAR1, by means of in vitro binding assay. BmMAR1 was identified to be specifically in vivo attached to the nuclear matrix only in the silkglands, neither in other tissues nor in the silkworm cell line Bm5, indicating its silkgland-relatedness. This 1983-bp DNA fragment contains a 1.1-kb core necessary for the effective in vitro binding although it is of relatively lower A/T composition (61%) compared to the 5' and 3' flanking regions (73 and 69%, respectively). Two degenerate sequences derived from Bm1 and L1Bm repetitive elements are located in the core region. BmMAR1 shares the widely considered typical MAR's features, DNA unwinding motif, A-box, T-box, H-box, replication origin, MAR recognition signature (MRS), the 90%AT box and Drosophila topoisomerase II consensus sequence. Furthermore we compared the occurrences of these patterns in BmMAR1 and some MARs from other organisms.

[Resections of tracheal or bronchial tumors and tracheal or bronchoplasty: experience with 53 patients].

UNLABELLED: From January 1982 to December 1992, a total of 485 patients with pulmonary tumors were treated by surgical procedure, in which 53 cases (92.4%) were treated by segmental resections of trachea, carina, bronchi and with tracheal-or bronchoplasty. In this series of tracheal-or bronchial tumors, four (7.6%) were benign, 49 (92.4%) were malignant. Segmental resections of trachea and carina with plastic procedures were performed on 6 cases, sleeve resections of main bronchi with plastic procedures were performed on 47 cases. One case (1.9%) died of respiratory failure postoperatively. FOLLOW-UP: the survival rate of 5 years was 35% (6/17), three years' was 56% (18/32), one year's was 77.8 (35/45). We considered that the patients with tumors of trachea or bronchi had significant symptom-irritated cough with bloody sputum. Earlier diagnosis, earlier surgical treatment could get a better therapeutic result. Segmental resections of trachea and sleeve resections of bronchi with lobectomy extended the indications for treating pulmonary neoplasm, and saved the normal lung tissues and functions as more as possible, provided some operative chances for elder patients and those cases with insufficient pulmonary functions. This procedure improved the patients's life quality and left the possibility of reoperation.

[Systematic study on the authentic and superior medicinal herba and GAP of herba asari].

OBJECTIVE: To investigate the methodology of the systematic study on the Authentic and Superior Medicinal Herba and GAP of Herba Asari. METHOD: The study was made by textual criticism of Herbology, Botany, Palynology, Cytology, Chemistry, Pharmacology, the analytic methods of allozyme and RAPD. Many subjects on the herb were investigated, such as history, botanical origin, routine examination, morphology of pollen, chromosome and karyotype, the content of oil and its pharmacological effects and so on. RESULT AND CONCLUSION: The methodology of systematic study on the Authentic and Superior Medicinal Herba was provided. According to the results of the systematic study, the GAP of the herb can be made.

Development of a low-cost magnetic microfluidic chip for circulating tumour cell capture.

The authors have developed a novel fabrication process for a selective micro-magnetic activated cell sorting (MACS) chip based on ferromagnetic material encapsulated micropillars (FMEMs), which is technically simple and low cost. The FMEM produces a high field gradient to magnetically attract, capture and hold cells on its interface. System test simulations were carried out to predict the efficacy of target capture and verify that the actual magnetic particles behaviour agreed well with model predictions. To determine the ability of the novel microMACS chip to capture circulating tumour cells (CTCs), SW620 human colon cancer cells were used in an in vitro flow model system and were able to be captured with the efficiency of 72.8%. The obvious accumulation of CTCs at a certain location on the chip suggested shear stress events at the pillar boundary may influence efficacy, and should be considered in further optimisation efforts.

Cloning of novel laccase isozyme genes from Trametes sp. AH28-2 and analyses of their differential expression.

Three novel laccase isozyme genes, lacA, lacB, and lacC, have been identified from basidiomycete Trametes sp. AH28-2. These genes display a high similarity with other basidiomycete laccases at the amino acid level. An inferred TATA box and several putative CAAT, MRE, XRE, and CreA consensus sequences were identified in the lacA, lacB, and lacC promoter regions. Different from the TATA boxes of lacA and lacB at about -100, the TATA box of lacC is located at -172. For all the isozymes, copper ion is essential for laccase synthesis in Trametes sp. AH28-2. More interestingly, different aromatic compounds can selectively induce the production of distinct laccase isozymes, with o-toluidine inducing the expression of laccase A (LacA) while 3,5-dihydroxytoluene mainly stimulating the production of laccase B (LacB). Quantitative reverse transcriptase-polymerase chain reaction showed that the accumulation of laccase messenger RNA transcripts is accompanied by the increase of corresponding enzyme activity in cultures. The glucose-repression effect on laccase expression in Trametes sp. AH28-2 was also observed. Furthermore, lower Cu2+ concentration (lower than 0.5 mM) can induce LacA and a novel laccase (LacC), and the latter will disappear when Cu2+ concentration is increased up to 1-2 mM. Upon induction by 3,5-dihydroxytoluene, the ratio of LacA to LacB decreased in the later phase of induction.

Silk fibroin: structural implications of a remarkable amino acid sequence.

The amino acid sequence of the heavy chain of Bombyx mori silk fibroin was derived from the gene sequence. The 5,263-residue (391-kDa) polypeptide chain comprises 12 low-complexity "crystalline" domains made up of Gly-X repeats and covering 94% of the sequence; X is Ala in 65%, Ser in 23%, and Tyr in 9% of the repeats. The remainder includes a nonrepetitive 151-residue header sequence, 11 nearly identical copies of a 43-residue spacer sequence, and a 58-residue C-terminal sequence. The header sequence is homologous to the N-terminal sequence of other fibroins with a completely different crystalline region. In Bombyx mori, each crystalline domain is made up of subdomains of approximately 70 residues, which in most cases begin with repeats of the GAGAGS hexapeptide and terminate with the GAAS tetrapeptide. Within the subdomains, the Gly-X alternance is strict, which strongly supports the classic Pauling-Corey model, in which beta-sheets pack on each other in alternating layers of Gly/Gly and X/X contacts. When fitting the actual sequence to that model, we propose that each subdomain forms a beta-strand and each crystalline domain a two-layered beta-sandwich, and we suggest that the beta-sheets may be parallel, rather than antiparallel, as has been assumed up to now.