The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and kidney stones: a cross-sectional study.

BACKGROUND: The relationship between the NHHR and kidney stone risk remains unknown. The purpose of this study was to evaluate the association between adult NHHR and kidney stone occurrence in USA. METHODS: This study used a variety of statistical techniques such as threshold effects, subgroup analysis, smooth curve fitting, multivariate logistic regression, and data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. We aimed to clarify the relationship between the NHHR and kidney stone risk. RESULTS: The average age of the 21,058 individuals in this research was 49.70 ± 17.64 years. The mean NHHR was 3.00 ± 1.47, and the overall prevalence of kidney stone occurrence was 9.05%. The prevalence within the quartile ranges (Q1-Q4) was 7.01%, 8.71%, 9.98%, and 10.49%, respectively. The overall average recurrence rate of kidney stones was 3.05%, demonstrating a significant increase with increasing NHHR (Q1: 1.92%, Q2: 2.92%, Q3: 3.35%, Q4: 4.00%, P < 0.01). The occurrence of kidney stones increased by 4% (95% CI: 1.00-1.08, P = 0.0373) and the chance of recurrence increased by 9% (95% CI: 1.03-1.14, P < 0.01) with each unit increase in NHHR. The interaction analysis results demonstrated that the relationship between the NHHR and the risk of kidney stones was not significantly impacted by the following factors: sex, body mass index, poverty income ratio, diabetes, or hypertension. Curve fitting and threshold effect analysis also demonstrated a non-linear association, with a breakpoint found at 3.17, between the NHHR and the risk of kidney stones. CONCLUSIONS: In adults in the USA, there is a substantial correlation between elevated NHHR levels and a higher probability of kidney stones developing and recurring. Timely intervention and management of NHHR may effectively mitigate the occurrence and recurrence of kidney stones.

An Additional L451G452N453 in the RpoB Protein Suppressed the Synthetic Lethality in Escherichia coli at 37 Degrees Caused by Depletion of DnaK/J and Trigger Factor.

Escherichia coli depletion of chaperone trigger factor and DnaK/J were not viable at 37°C, but viable below 30°C. Among the engineered E. coli depleted of trigger factor and DnaK/J, one strain Z625, exhibited survival at 37°C, while another strain Z629 only survived below 30°C. Comparative analysis of fatty acid profiles of Z625 and Z629 revealed absence of numerous saturated fatty acids in Z625 as compared to the wild-type E. coli BW25113. In addition, increased unsaturated fatty acids were present in Z625, whereas the fatty acids profile of Z629 closely resembled that of BW25113. Whole genome sequencing revealed a 9-bp insertion in rpoB of Z625. Combined structural analysis of simulated RpoB protein bearing the amino acid sequence L451G452N453 insertion and susceptibility analysis to rifampicin suggested that the insertion did not disturb the individual RpoB structure as beta subunit of RNA polymerase. Comparative transcriptomic analysis of Z625 and Z629 suggested that this insertion impacted transcription of the overall RNA polymerase in Z625, leading to potential repression of some genes whose overexpression was toxic to E. coli. Additionally, Z625 exhibited distinctive metabolic adaptations, likely contributing to its survival at 37°C. In summary, our study elucidated one LGN insertion in rpoB that impacts transcriptional regulation in E. coli, thereby explaining the survival of E. coli depletion of trigger factor and DnaK/J at 37°C, and these founding suggested that some simple mutations in critical genes like rpoB might play an important role in driving adaptive evolution.

Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer.

BACKGROUND: In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described. METHODS: This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis. RESULTS: Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133-42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811-4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015-3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728-2.806, P = 0.294). CONCLUSIONS: We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

Association Between Head and Neck Cancers and Polymorphisms 869T/C, 509C/T, and 915G/C of the Transforming Growth Factor-ß1 Gene: A Meta-Analysis of Case-Control Studies.

BACKGROUND Worldwide, head and neck cancers are the eighth most common malignancy. Single nucleotide polymorphisms (SNPs) are associated with susceptibility to cancer and sensitivity to radiotherapy and chemotherapy. The inflammatory cytokine, transforming growth factor-ß1 (TGF-ß1), is involved in the progression of malignancy. This study aimed to systematically review the literature and undertake a meta-analysis of case-control studies on the association between 869T/C, 509C/T, and 915G/C polymorphisms of the TGF-ß1 gene and head and neck cancers. MATERIAL AND METHODS The published literature in the English and Chinese languages were searched to identify relevant studies reporting TGF-ß1 gene polymorphisms and head and neck cancer. The PubMed, Embase, Wanfang Data, and CNKI databases were searched. Data were extracted from eligible studies, and meta-analysis was performed using Stata version 12.0 software. RESULTS Ten case-control studies were identified. There was a significant association between the 869T/C polymorphism of the TGF-ß1 gene and susceptibility to head and neck cancer. Subgroup analysis showed that the 869T/C polymorphism was not significantly associated with the histological type of head and neck cancer, but was significantly associated with susceptibility to head and neck cancer in the Asian population. The 509C/T polymorphism of the TGF-ß1 gene was not significantly associated with susceptibility to nasopharyngeal cancer (NPC), but the 915G/C polymorphism was associated with susceptibility to oral cancer. CONCLUSIONS Data from this meta-analysis showed that the 869T/C and 915G/C polymorphisms of the TGF-ß1 gene might be associated with susceptibility to head and neck cancer.

Development of the photosynthetic apparatus of Cunninghamia lanceolata in light and darkness.

Here, we compared the development of dark- and light-grown Chinese fir (Cunninghamia lanceolata) cotyledons, which synthesize chlorophyll in the dark, representing a different phenomenon from angiosperm model plants. We determined that the grana lamellar membranes were well developed in both chloroplasts and etiochloroplasts. The accumulation of thylakoid membrane protein complexes was similar between chloroplasts and etiochloroplasts. Measurement of chlorophyll fluorescence parameters indicated that photosystem II (PSII) had low photosynthetic activities, whereas the photosystem I (PSI)-driven cyclic electron flow (CEF) rate exceeded the rate of PSII-mediated photon harvesting in etiochloroplasts. Analysis of the protein contents in etiochloroplasts indicated that the light-harvesting complex II remained mostly in its monomeric conformation. The ferredoxin NADP+ oxidoreductase and NADH dehydrogenase-like complexes were relatively abundantly expressed in etiochloroplasts for Chinese fir. Our transcriptome analysis contributes a global expression database for Chinese fir cotyledons, providing background information on the regulatory mechanisms of different genes involved in the development of dark- and light-grown cotyledons. In conclusion, we provide a novel description of the early developmental status of the light-dependent and light-independent photosynthetic apparatuses in gymnosperms.

Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods.

Roots of Arabidopsis thaliana seedlings grown in the laboratory using the traditional plant-growing culture system (TPG) were covered to maintain them in darkness. This new method is based on a dark chamber and is named the improved plant-growing method (IPG). We measured the light conditions in dark chambers, and found that the highest light intensity was dramatically reduced deeper in the dark chamber. In the bottom and side parts of dark chambers, roots were almost completely shaded. Using the high-throughput RNA sequencing method on the whole RNA extraction from roots, we compared the global gene expression levels in roots of seedlings from these two conditions and identified 141 differently expressed genes (DEGs) between them. According to the KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, the flavone and flavonol biosynthesis and flavonoid biosynthesis pathways were most affected among all annotated pathways. Surprisingly, no genes of known plant photoreceptors were identified as DEGs by this method. Considering that the light intensity was decreased in the IPG system, we collected four sections (1.5 cm for each) of Arabidopsis roots grown in TPG and IPG conditions, and the spatial-related differential gene expression levels of plant photoreceptors and polar auxin transporters, including CRY1, CRY2, PHYA, PHYB, PHOT1, PHOT2, and UVR8 were analyzed by qRT-PCR. Using these results, we generated a map of the spatial-related expression patterns of these genes under IPG and TPG conditions. The expression levels of light-related genes in roots is highly sensitive to illumination and it provides a background reference for selecting an improved culture method for laboratory-maintained Arabidopsis seedlings.

Screening and Validation of Housekeeping Genes of the Root and Cotyledon of Cunninghamia lanceolata under Abiotic Stresses by Using Quantitative Real-Time PCR.

Cunninghamia lanceolata (Chinese fir) is a fast-growing and commercially important conifer of the Cupressaceae family. Due to the unavailability of complete genome sequences and relatively poor genetic background information of the Chinese fir, it is necessary to identify and analyze the expression levels of suitable housekeeping genes (HKGs) as internal reference for precise analysis. Based on the results of database analysis and transcriptome sequencing, we have chosen five candidate HKGs (Actin, GAPDH, EF1a, 18S rRNA, and UBQ) with conservative sequences in the Chinese fir and related species for quantitative analysis. The expression levels of these HKGs in roots and cotyledons under five different abiotic stresses in different time intervals were measured by qRT-PCR. The data were statistically analyzed using the following algorithms: NormFinder, BestKeeper, and geNorm. Finally, RankAggreg was applied to merge the sequences generated from three programs and rank these according to consensus sequences. The expression levels of these HKGs showed variable stabilities under different abiotic stresses. Among these, Actin was the most stable internal control in root, and GAPDH was the most stable housekeeping gene in cotyledon. We have also described an experimental procedure for selecting HKGs based on the de novo sequencing database of other non-model plants.

Survival and Prognostic Analysis of Primary Nasopharyngeal Carcinoma in North China.

BACKGROUND: To investigate the prognostic factors of Nasopharyngeal Carcinoma (NPC). METHODS: Retrospective analysis was carried out on the clinical data collected from three hospitals in North China between September, 1999 to March, 2012. RESULTS: Higher survival rates (1, 3, 5, and 10 year) were found in NPC patients who were female, non-smokers, early clinical phase, and T1-2 (p < 0.05). No association was found between survival rates and drinking habits, lesion location, pathological types, N stages, and radiotherapy pattern. The 1-, 3-, and 5-year overall survival rates were equal following both conventional radiotherapy and Intensity-Modulating Radiotherapy (IMRT). CONCLUSIONS: Patient gender, age, smoking status, clinical stages, and T stages all served as prognostic factors of nasopharyngeal carcinoma.

Adiponectin Gene Polymorphisms are Associated with Increased Risk of Colorectal Cancer.

BACKGROUND: This meta-analysis investigates the associations of adiponectin (ADIPOQ) genetic polymorphisms with the susceptibility to colorectal cancer (CRC). MATERIAL AND METHODS: 2 reviewers independently searched 6 databases - PubMed, Cochrane Library, Ovid, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases - to identify published studies relevant to adiponectin gene polymorphisms and CRC. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria. Full texts of the selected studies were accessed and related data was extracted using a standardized data extraction form. Comprehensive Meta-analysis 2.0 software was used for statistical analyses. RESULTS: A total of 188 studies were initially retrieved from database search, and 6 studies were eventually selected, through a rigorous screening process, for inclusion in this meta-analysis. The 6 studies contained a total of 1897 patients (Asians: 1190; white: 707) with CRC in case group and 2475 healthy controls (Asians: 1325; white: 1150) in the control group. Results of the current meta-analysis revealed that the rs2241766 T>G single-nucleotide polymorphisms (SNP) increase the risk of CRC; rs1501299 G>T under dominant model was associated with increased risk of CRC; and rs266729 C>G SNP under allele model conferred an increased risk of CRC. CONCLUSIONS: Our meta-analysis strongly suggests that the ADIPOQ rs2241766 T>G, rs1501299 G>T, and rs266729 C>G SNPs correlate with an increased risk of CRC.

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer.

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFß1 -869 T/C, IL-6 -634C/G, TGFß1 -509C/T, IL1 -511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a -889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a -889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G + G/G of IL6 -634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a -889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 -634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.

Immune checkpoint inhibitors for patients with mismatch-repair deficient or microsatellite instability-high advanced cancers: a meta-analysis of phase I-III clinical trials.

BACKGROUND: Mismatch-repair deficient (dMMR) and microsatellite instability-high (MSI-H) cancers are associated with an increased number of somatic mutations, which can render tumors more susceptible to immune checkpoint blockade. However, a comprehensive evaluation of the efficacy profile of immune checkpoint inhibitors in this patient population across multiple cancer types is lacking. This study aims to address this knowledge gap by synthesizing data from Phase I-III clinical trials. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Google Scholar from inception until June, 2024. Eligible studies included randomized controlled trials (RCTs), non-randomized comparative studies, and single-arm trials investigating immune checkpoint inhibitors in patients with dMMR/MSI-H advanced cancers. The primary outcome was objective response rate (ORR), and the secondary outcomes included disease control rate (DCR), 1-year, 2-year, and 3-year overall survival (OS) and progression-free survival (PFS) rates. Subgroup analyses were conducted for the primary outcome stratified by major study characteristics. RESULTS: Of the 10802 identified studies, 19 trials in 25 studies totaling 2052 participants met the inclusion criteria and were included in the meta-analysis. The pooled ORR was 41.7% (95% CI, 35.7%-47.7%). The pooled DCR was 68.9% (95% CI, 62.2%-75.7%). The pooled 12-month, 24-month and 36-month OS rates were 29.1% (95% CI, 19.9%-38.3%), 35.8% (95% CI, 23.6%-48.0%), and 35.8% (95% CI, 23.6%-48.0%), respectively. The pooled 12-month, 24-month and 36-month PFS rates were 46.4% (95% CI, 39.1%-53.8%), 67.0% (95% CI, 55.2%-78.8%), and 63.1% (95% CI, 37.3%-88.9%), respectively. CONCLUSIONS: The study establishes the therapeutic potential of immune checkpoint inhibitors in dMMR/MSI-H advanced cancers, highlighting the importance of MSI status in this context. Further head-to-head comparisons are needed to conclusively determine MSI's predictive power relative to proficient mismatch-repair/ microsatellite stable (pMMR/MSS) tumors.

Camrelizumab combined with apatinib for unresectable, metastatic esophageal squamous cell carcinoma: a single-center, single-arm, prospective study.

Background: The prognosis for esophageal cancer (EC), a common malignant tumor, is poor. The new oral small-molecule tyrosine kinase inhibitor apatinib has shown an excellent therapeutic effect on treating EC. Camrelizumab is a humanized programmed death 1 (PD-1) inhibitor with high affinity. Immune checkpoint inhibitors combined with chemotherapy have become the standard first-line treatment for advanced EC. The new combination strategy of anti-angiogenic therapy combined with immunotherapy has great application prospects in the treatment of tumors. We aimed to assess camrelizumab in combination with apatinib as a new combination regimen for advanced or metastatic esophageal squamous cell carcinoma (ESCC). Methods: In this study, we recruited patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with pathologically confirmed unresectable, locally advanced, locally recurrent, or metastatic ESCC. Each patient received an intravenous infusion of camrelizumab 200 mg and oral administration of apatinib 250 mg once a day, every 21 days, as a cycle until disease progression, intolerance, or death. The primary endpoint was the objective response rate (ORR), while the Kaplan-Meier method and LIFETEST procedure were used to estimate survival functions for overall survival (OS) and progression-free survival (PFS). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used to evaluate adverse events. Results: Between December 1, 2019 and July 31, 2022, 35 patients were enrolled, with 29 patients in the efficacy and safety analysis. The ORR was 34.5%, and the disease control rate (DCR) reached 82.8%. Median OS was 13.8 months (95% CI: 11.2-16.2), and the estimated 6-, 9-, and 12-month OS rates were 85.5% (95% CI: 65.7-94.3%), 80.9% (95% CI: 60.3-91.5%), and 67.0% (95% CI: 43.8-82.4%), respectively. Median PFS was 9.5 months (95% CI: 7.0-13.6). The most prominent grade ≥3 adverse events associated with treatments were alanine aminotransferase (ALT) increase (10.3%), hypertension (10.3%), and reactive cutaneous capillary endothelial proliferation (CCEP) (6.9%), and no deaths occurred due to adverse events. Conclusions: Among patients with advanced or metastatic ESCC, camrelizumab combined with apatinib showed a reasonable remission rate and survival benefit with a manageable safety profile.

High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC. METHODS: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003. FINDINGS: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit. INTERPRETATION: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option. FUNDING: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program.

Post-irradiation intratumoral heterogeneity modulates response to immune checkpoint inhibition therapy in a murine melanoma model.

PURPOSE: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. EXPERIMENTAL DESIGN: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. RESULTS: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. CONCLUSIONS: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI.

Optimizing Whole Brain Radiotherapy Treatment and Dose for Patients With Brain Metastases From Small Cell Lung Cancer.

PURPOSE: This study aimed to evaluate the survival outcomes of whole brain radiotherapy (WBRT) compared to whole brain radiotherapy plus local radiation boost (WBRT + boost), and further identify whether higher biologically effective dose (BED) of WBRT + boost translates into a survival benefit in small cell lung cancer (SCLC) patients with brain metastasis (BM). METHODS: SCLC patients with BM from January 1, 2012, to December 31, 2019, were retrospectively analyzed. Overall survival (OS) and intracranial progression-free survival (iPFS) were evaluated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate regression analyses of prognostic factors for OS were performed using Cox proportional hazards regression models. The cutoff value of BED was determined by the receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 180 eligible patients, 82 received WBRT + boost and 98 received WBRT. Both OS and iPFS in the WBRT + boost group were significantly superior to those in the WBRT group (median OS: 20 vs. 14 months, p = 0.011; median iPFS: 16 vs. 10 months, p = 0.003). At a cutoff value of 58.35 Gy in the WBRT + boost group, 52 for the high-BED (>58.35 Gy) group, 30 for the low-BED (≤58.35 Gy) group. High BED was significantly associated with improved OS and iPFS compared with low BED in the WBRT + boost group (median OS: 23 vs. 17 months, p = 0.002; median iPFS: 17 vs. 10 months, p = 0.002). CONCLUSIONS: Compared with WBRT alone, WBRT + boost improved OS and iPFS in SCLC patients with BM. High BED (>58.35 Gy) for WBRT + boost may be a reasonable consideration for SCLC patients with BM.

Molecular Mechanism of Expression Changes of Immunological Indexes of PD-1/sPD-L1 after Radiotherapy in Nonsmall Cell Lung Cancer.

It is aimed at investigating the changes of serum soluble programmed death-ligand 1 (sPD-L1) expression level in nonsmall cell lung cancer (NSCLC) before and after radiotherapy, the correlation of PD-L1, PD-1, and proteins of Akt (protein kinase B), mTOR, and HIF-1α, and the molecular mechanism of the PD-1/PD-L1 pathway in the development of NSCLS. A total of 126 NSCLC patients receiving radiotherapy in Liaoning Cancer Hospital from September 2018 to September 2019 were selected as the observation group, and another 58 healthy volunteers were selected as the control group. NSCLC patients were divided into group A (stage I-II, stereotactic radiotherapy) and group B (stage III, intensity-modulated radiation therapy) according to the cancer stage. The efficacy of radiotherapy was evaluated, and sPD-L1 expression was detected by ELISA. The immunohistochemical staining was adopted to detect protein expressions of Akt, mTOR, and HIF-1α in NSCLC tissues. The correlation between their expression and expression of PD-L1 and PD-1 was analyzed. The results showed that the overall response rate (ORR) of group A was 89.29%, the clinical benefit response (CBR) was 96.43%, the median survival time (MST) was 25 months, and the survival rate within three years was 72.56%. In group B, the ORR was 70.41%, the CBR was 97.96%, the MST was 18 months, and the survival rate within three years was 34.67%. Comparison of overall serum sPD-L1 expression in the control group, group A, and group B and between groups before radiotherapy was statistically significant (P < 0.01). After radiotherapy, serum sPD-L1 expression in group A and group B decreased compared with that before radiotherapy (P < 0.01). Among NSCLC patients, the positive expression rate of Akt, mTOR, and HIF-1α was 71.32%, 41.26%, and 80.65%, respectively. PD-L1 expression and Akt, mTOR, and HIF-1α expression showed a significant correlation. PD1 expression and Akt, mTOR, and HIF-1α expression also showed a significant correlation. It indicated that the expression level of sPD-L1 in NSCLC patients was higher than that in normal subjects, but the expression level of sPD-L1 was decreased after radiotherapy. PD-1/PD-L1 may play important roles in NSCLC procession through the Akt/mTOR and HIF-1α pathway.

Prognostic nutritional index and systemic immune-inflammation index are prognostic biomarkers for non-small-cell lung cancer brain metastases.

Aim: This research aimed to elucidate the prognosis values of prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) and clinical characteristics in NSCLC patients with brain metastases (BM) underwent radiotherapy. Materials & methods: Cut-off points of hematological indicators were determined by receiver operating characteristic curve. Overall survival was evaluated by Kaplan-Meier method and Cox proportional hazards model. Results: We retrospectively analyzed 214 patients from January 2009 to December 2018. The result demonstrated the independent prognostic values of PNI (hazard ratio: 0.600; p = 0.004) and SII (hazard ratio: 1.486; p = 0.019). The remaining clinicopathologic factors, including brain radiotherapy modality, smoking history, numbers of brain metastases, intracranial symptoms and Radiation Therapy Oncology Group - recursive partitioning analysis, were independently related to survival (p < 0.05). Conclusion: PNI and SII could be critical prognostic indicators for NSCLC patients with BM.

Single nucleotide polymorphisms in breast cancer susceptibility gene 1 are associated with susceptibility to lung cancer.

BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student's t-test, a χ2 test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.

Pneumonitis, appendicitis, and biliary obstruction during toripalimab treatment in a patient with extensive-stage small-cell lung cancer: a case report.

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.