Genome-wide association study of 7661 Chinese Han individuals and fine-mapping major histocompatibility complex identifies HLA-DRB1 as associated with IgA vasculitis.

BACKGROUND: Immunoglobulin-A vasculitis (IgAV) is an immune-related systemic vasculitis with an unclear etiology. Genetic predisposition is now considered to be closely associated with the development of the disease, and it is essential to reveal the relationship between them. To explore the role of heredity in the disease, we performed a genome-wide association study (GWAS) of 496 IgAV cases and 7165 controls using an Illumina Infinium Global Screening Array chip. METHODS: In the first stage of analysis, a significant correlation between the major histocompatibility complex (MHC) and IgAV was observed. Subsequently, human leukocyte antigen (HLA) analysis was conducted using a new large-scale Han-MHC reference panel. Fine mapping of IgAV risk in the MHC region indicated that two amino acid positions, 120 and 11, of HLA-DRB1 and three potential HLA alleles (HLA-DRB1∗04, HLA-DRB1∗16, and HLA-DRB1∗16:02) were significantly associated. RESULTS: Further stepwise conditional analysis demonstrated that 3 amino acid positions (120, 26, 96) of HLA-DRB1 and 6 HLA-DRB1 alleles (HLA-DRB1*04, HLA-DRB1*16, HLA-DRB1*01, HLA-DRB1*12:02, HLA-DRB1*10, and HLA-DRB1*15:02) were independent signals. Among them, the most significant signal was HLA-DRB1 amino acid Ser120 (OR = 1.59, p = 3.19 × 10-8 ); no independent signal in the MHC region except for HLA-DRB1 was found. CONCLUSIONS: Our study confirms that the pathogenesis of IgAV has a genetic component and that HLA-DRB1 is strongly associated with susceptibility to IgAV.

Copy Number Variation Analysis of IL22 and LCE3C in Different Subtypes of Psoriasis in a Chinese Han Population.

BACKGROUND Psoriasis is a chronic, immune-mediated and hyperproliferative skin disease with both genetic and environmental components. Copy number variations (CNV) of IL22 and LCE3C-LCE3B deletion have been confirmed to be predisposed to psoriasis vulgaris (PsV) in several ethnic groups. However, it remains to be clarified whether CNVs of IL22 and LCE3C are associated with different subtypes of psoriasis (psoriatic arthritis, PsA; erythrodermic psoriasis, EP; and generalized pustular psoriasis, GPP). MATERIAL AND METHODS We enrolled 897 Han Chinese individuals, including 478 patients and 419 healthy controls, and detected CNVs of IL22 and LCE3C using the comparative CT method by real-time PCR, and Pearson's χ² test was used to evaluated the copy number difference among subtypes. RESULTS CNVs of IL22 were significantly higher in PsV than in healthy controls (P<0.001). CNV of LCE3C in PsV, PsA, and GPP groups were significantly lower compared to healthy controls. When linked with clinical parameters, mild psoriasis carried less IL22 copy numbers than that in severe psoriasis (P=0.043). Neither IL22 or LCE3C CNVs were associated with age of onset. CONCLUSIONS CNVs of LCE3C and IL22 might differentially contribute to subtypes of psoriasis. These findings suggest complex and diverse genetic variations in and among different clinical subtypes of psoriasis.

Systematic review of the registered clinical trials for coronavirus disease 2019 (COVID-19).

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.

Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K.

OBJECTIVE: This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. METHODS: Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and apoptosis in B cells, respectively. RESULTS: Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted apoptosis of B cells from SLE patients, whereas BCR-ABL dramatically reversed cell changes induced by Bach2. Besides, BCR-ABL also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by BCR-ABL, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by BCR-ABL in B cells from SLE. CONCLUSIONS: Bach2 may play a suppressive role in B cells from SLE, and BCR-ABL may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway.

Noninvasive analysis of skin proteins in healthy Chinese subjects using an Orbitrap Fusion Tribrid mass spectrometer.

OBJECTIVE: The objective of this study was to perform noninvasive analysis of skin proteins in a healthy Chinese population using label-free nanoflow liquid chromatography-mass spectrometry (nLC-MS). MATERIALS AND METHODS: Five consecutive tape strippings were obtained from the volar forearm skin of healthy Chinese subjects. Proteins were extracted, and trypsin-digested peptides were analyzed by a nanochromatography instrument coupled to an Orbitrap Fusion Tribrid mass spectrometer. Data-dependent acquisition allowed protein identification, which was performed by using Proteome Discoverer software (v2.2). RESULTS: In this study, we identified 80 common proteins that were expressed in the skin of healthy Chinese volunteers and divided these proteins into 16 categories, including keratins, cornified envelope proteins, and enzymes associated with substance metabolism. These proteins were closely associated with multiple functions of the skin barrier. CONCLUSION: This study provides a noninvasive method to analyze healthy human epidermal proteins, which are closely associated with the skin barrier. In addition, this study provides a reference for further studies on the application of proteomic technologies to investigate the role of human epidermal proteins in health and disease.

Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. METHODS: We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. RESULTS: We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10-8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10-3) whose expression level was reduced significantly in patients with SLE (P<2.53×10-2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10-5) in ex vivo experiments. CONCLUSIONS: This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.

NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis.

This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways.

OBJECTIVE: Endometrial carcinoma is one of the most common malignancies of the female reproductive system, but the aetiology and pathogenesis are not well understood, although adipokines such as visfatin may be involved. Our study provides insight into the mechanism underlying the tumorigenic effects of visfatin in endometrial carcinoma. METHODS: We investigated the effect of visfatin on endometrial carcinoma cell proliferation, cell cycle, and apoptosis using well-differentiated Ishikawa cells and poorly differentiated KLE cells. We also assessed the effect of visfatin on tumour growth in vivo. RESULTS: Visfatin stimulated the proliferation of both Ishikawa and KLE cells, and visfatin treatment promoted G1/S phase progression and inhibited endometrial carcinoma cell apoptosis. Visfatin promoted endometrial carcinoma tumour growth in BALB/c-nu mice. Transplanted tumour tissues from an endometrial carcinoma mouse model were analysed using immunohistochemical staining, which revealed much stronger positive signals for Ki-67 with over-abundant visfatin. Western blot analysis revealed that insulin receptor (IR), insulin receptor substrate (IRS)1/2 and key components of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2 signalling pathways were highly expressed in endometrial carcinoma cells exposed to visfatin. Treated cells showed increased C-MYC and cyclin D1 and reduced caspase-3 expression. The effects of visfatin on proliferation and apoptosis were abrogated by treatment with the PI3K inhibitor LY294002 and MEK inhibitor U0126. CONCLUSIONS: Visfatin promotes the malignant progression of endometrial carcinoma via activation of IR and PI3K/Akt and MAPK/ERK signalling. Visfatin may serve as a therapeutic target in the treatment of endometrial carcinoma.

Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

A comprehensive association analysis confirms ZMIZ1 to be a susceptibility gene for vitiligo in Chinese population.

BACKGROUND: ZMIZ1 has been shown to be associated with multiple autoimmune diseases and play a role in the development of melanocyte. The association of ZMIZ1 with vitiligo was also suggested, but the evidence did not reach genome-wide significance and has not been confirmed by independent studies. METHODS: A fine mapping analysis of the ZMIZ1 locus was carried out in the dataset of 1117 vitiligo patients and 3437 controls through deep imputation. Ten suggestive SNPs were then analysed in an independent validation cohort of 7458 cases and 7542 controls. SNPs within ZMIZ1 locus were functionally annotated using the ENCODE and RegulomeDB databases and published eQTL dataset of primary immune cells. RESULTS: A genome-wide significant association was discovered at rs1408944 (OR(combined)=1.18, p(combined)=1.38E-09) that locates at a DNAse hypersensitivity site and within a Myb_1 motif carried by the binding sites of six overlapping transcription factors (TFs) within the region. Gene Relationships Across Implicated Loci (GRAIL) analysis revealed biological connectivity between ZMIZ1 and previously discovered susceptibility loci for vitiligo as well as the six TFs. CONCLUSIONS: Our study has confirmed ZMIZ1 as a novel susceptibility locus for vitiligo and further suggested rs1408944 to be the putative causal variant that potentially interrupts TF binding and thus the transcriptional regulation of ZMIZ1.

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis.

BACKGROUND: Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. METHODS: The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. RESULTS: An average of 1.35×10(5) variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. CONCLUSIONS: The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population.

BACKGROUND: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. METHODS: In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. RESULTS: We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9)). CONCLUSIONS: These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.

Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population.

Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.

A 66-Nuclear All-Alkynyl Protected Peanut-Shaped Silver(I)/Copper(I) Heterometallic Nanocluster: Intermediate in Copper-Catalyzed Alkyne-Azide Cycloaddition.

Ligand-protected heterometallic nanoclusters in contrast to homo-metal counterparts show more broad applications due to the synergistic effect of hetero-metals but their controllable syntheses remain a challenge. Among heterometallic nanoclusters, monovalent Ag-Cu compounds are rarely explored due to much difference of Ag(I) and Cu(I) such as atom radius, coordination habits, and redox potential. Encouraged by copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, comproportionation reaction of Cu(II)X2 and Cu(0) in the presence of (PhC≡CAg)n complex and molybdate generated a core-shell peanut-shaped 66-nuclear Ag(I)-Cu(I) heterometallic nanocluster, [(Mo4O16)2@Cu12Ag54(PhC≡C)50] (referred to as Ag54Cu12). The structure and composition of Ag-Cu heterometallic nanocluster are fully characterized. X-ray single crystal diffraction reveals that Ag54Cu12 has a peanut-shaped silver(I)/copper(I) heterometallic nanocage protected by fifty phenylacetylene ligands in µ3-modes and encapsulated two mutually twisted tetramolybdates. Heterometallic nanocage contains a 54-Ag-atom outer ellipsoid silver cage decorated by 12 copper inside wall. Nanosized Ag54Cu12 is a n-type narrow-band-gap semiconductor with a good photocurrent response. Preliminary experiments demonstrates that Ag54Cu12 itself and activated carbon supported Ag54Cu12/C are effective catalysts for 1,3-dipole cycloaddition between alkynes and azides at ambient conditions. The work provides not only a new synthetic route toward Ag(I)-Cu(I) nanoclusters but also an important heterometallic intermediate in CuAAC catalytic reaction.

Plant-based dietary patterns and lung cancer mortality: a perspective cohort study.

Plant-based diets are recommended for cancer survivors; however, their effects on lung cancer mortality are limited. We conducted this study to evaluate the association between plant-based dietary patterns and lung cancer mortality. A total of 408 newly diagnosed lung cancer patients aged 18 to 79 years were enrolled in the study. Dietary intake was assessed using a validated 111-item food frequency questionnaire (FFQ). The survival status was confirmed by medical records and an active follow-up until March 31, 2023. We calculated three dietary indices: the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of plant-based indices with lung cancer mortality. During the follow-up period (median: 40.97 months; interquartile: 29.77-45.63 months), 240 patients died from lung cancer. An inverse association was observed between hPDI scores and lung cancer mortality (Q4 vs. Q1, HR, 0.66, 95% CI, 0.45-0.97, the P value for trend, 0.042), while each 10-unit increment was associated with a decreased risk of lung cancer mortality (HR, 0.75; 95% CI, 0.57-0.99). Regarding PDI and uPDI, no significant association was found with lung cancer mortality. Our study suggests that adherence to a diet with a high hPDI score may reduce lung cancer mortality.

Cancer of unknown primary site in the mandibular region: A case report.

The diagnosis and treatment of cancer of unknown primary site (CUP) present with difficulties and produce a poor prognosis. The current study presents the case of a patient with CUP in the mandibular region was treated with docetaxel and lobaplatin chemotherapy, and vascular embolization of the tumor. The tumor size was markedly reduced and the patient's quality of life improved following radiotherapy. The present case report is accompanied by a discussion of the literature to contextualize the treatment regimen for patients with CUP. These findings will support current treatment practices, inform oncologists and benefit patients with cancer.

Manipulating the Alkyl Chains of Naphthodithiophene Imide-Based Polymers to Concurrently Boost the Efficiency and Stability of Organic Solar Cells.

Morphology instability holds the major responsibility for efficiency degradation of organic solar cells (OSCs). However, how to develop polymer donors simultaneously with high efficiency and excellent morphology stability remains challenging. Herein, we reported naphtho[2,1-b:3,4-b']dithiophene-5,6-imide (NDTI)-based new polymers PNDT1 and PNDT2. The alkyl chain engineering leads to high crystallinity, high hole mobility (>10-3 cm2 V-1 S-1), and nanofibrous film morphology, which enable PNDT2 to exhibit an efficiency of 18.13% and a remarkable FF value of 0.80. Moreover, the NDTIs have short π-π stacking and abundant short interactions, and their polymers exhibit superior morphological stability. Therefore, the PNDT2-based OSCs exhibit much better device stability than that of PNDT1, PAB-α, and benchmark polymers PM6 and D18. This work suggests the great importance of the large conjugated backbone of the monomer and alkyl chain engineering to develop high-performance and morphology-stable polymers for OSCs.