Search

Summary: The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index

Abstract Developing efficient metal‐nitrogen‐carbon (M‐N‐C) single‐atom catalysts for oxygen reduction reaction (ORR) is significant for the widespread implementation of Zn‐air batteries, while the synergic design of the matrix microstructure and coordination environment of metal centers remains challenges. Herein, a novel salt effect‐induced strategy is proposed to engineer N and P coordinated atomically dispersed Fe atoms with extra‐axial Cl on interlinked porous carbon nanosheets, achieving a superior single‐atom Fe catalyst (denoted as Fe‐NP‐Cl‐C) for ORR and Zn‐air batteries. The hierarchical porous nanosheet architecture can provide rapid mass/electron transfer channels and facilitate the exposure of active sites. Experiments and density functional theory (DFT) calculations reveal the distinctive Fe‐N2P2‐Cl active sites afford significantly reduced energy barriers and promoted reaction kinetics for ORR. Consequently, the Fe‐NP‐Cl‐C catalyst exhibits distinguished ORR performance with a half‐wave potential (E1/2) of 0.92 V and excellent stability. Remarkably, the assembled Zn‐air battery based on Fe‐NP‐Cl‐C delivers an extremely high peak power density of 260 mW cm−2 and a large specific capacity of 812 mA h g−1, outperforming the commercial Pt/C and most reported congeneric catalysts. This study offers a new perspective on structural optimization and coordination engineering of single‐atom catalysts for efficient oxygen electrocatalysis and energy conversion devices.

The disordered growth, invasion and metastasis of cancer are mainly attributed to bidirectional cell-cell interactions. Extracellular vesicles (EVs) secreted by cancer cells are involved in orchestrating the formation of pre-metastatic niches (PMNs). Tumor-derived EVs mediate bidirectional communication between tumor and stromal cells in local and distant microenvironments. EVs carrying mRNAs, small RNAs, microRNAs, DNA fragments, proteins and metabolites determine metastatic organotropism, enhance angiogenesis, modulate stroma cell phenotypes, restructure the extracellular matrix, induce immunosuppression and modify the metabolic environment of organs. Evidence indicates that EVs educate stromal cells in secondary sites to establish metastasis-supportive microenvironments for seeding tumor cells. In this review, we provide a comprehensive overview of PMN formation and the underlying mechanisms mediated by EVs. Potential approaches to inhibit cancer metastasis by inhibiting the formation of PMNs are also presented.

IntroductionColorectal cancer (CRC) is the third most common malignant tumor, and neoadjuvant chemo-radiotherapy is usually recommended for advanced stage colorectal cancer. Radiotherapy can cause damage to intestinal mucosal barrier, which may be related to perioperative complications. Intestinal microbiota is one of the constituents of the intestinal mucosal biological barrier, and literature reports that patients with CRC have changes in corresponding oral microbiota. This study aims to analyze the levels of immunoglobulin SIgA, inflammatory factors, lymphocyte subsets quantity, and proportion in surgical specimens of intestinal mucosa at different time intervals after radiotherapy, in order to seek investigation for the optimal surgical time after radiotherapy and to provide evidence for finding probiotics or immunomodulators through high-throughput sequencing of bacterial 16s rRNA in patients' saliva microbiota. Ultimately, this may provide new ideas for reducing perioperative complications caused by radiotherapy-induced intestinal damage.MethodsWe selected intestinal mucosal tissue and saliva samples from over 40 patients in our center who did not undergo radiotherapy and underwent surgery at different time intervals after radiotherapy. Detection of SIgA was performed using ELISA assay. Western Blotting was used to detect IL-1β, IL-6, and IL-17 in the intestinal mucosal tissue. Flow cytometry was used to detect CD4 and CD8. And the microbial community changes in saliva samples were detected through 16s rRNA sequencing.ResultsAfter radiotherapy, changes in SIgA, various cytokines, CD4CD8 lymphocyte subsets, and oral microbiota in the intestinal mucosal tissue of rectal cancer patients may occur. Over time, this change may gradually recover.DiscussionIn colorectal cancer, oncological aspects often receive more attention, while studies focusing on the intestinal mucosal barrier are less common. This study aims to understand the repair mechanisms of the intestinal mucosal barrier and reduce complications arising from radiotherapy-induced damage. The relationship between oral microbiota and systemic diseases has gained interest in recent years. However, the literature on the oral microbiota after radiotherapy for rectal cancer remains scarce. This study addresses this gap by analysing changes in the salivary microbiota of rectal cancer patients before and after radiotherapy, shedding light on microbiota changes. It aims to lay the groundwork for identifying suitable probiotics or immunomodulators to alleviate perioperative complications and improve the prognosis of CRC.

Introduction: Female-specific cancers seriously affect physical and psychological health of women worldwide. Objectives: We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) of breast cancer, cervical cancer, uterine cancer, and ovarian cancer in female populations with different socioeconomic statuses in China and in countries with different Human Development Index (HDI). Methods: A longitudinal study was performed using the data of cancer death in China and other 39 countries. The mortality rates were standardized with the Segi’s world population. Trends in the mortalities were exhibited by estimated annual percentage change (EAPC). Pearson correlation was used to assess the association between EAPC and HDI. Results: In mainland China, female breast cancer, cervical cancer, uterine cancer, and ovarian cancer accounted for 6.60 %, 4.21 %, 2.50 %, and 2.02 % of cancer death (n = 1,314,040) in women with 1,220,251,032 person-years, respectively. The ASMRs of cervical cancer (EAPC = 3.87 %, P

Abstract Clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with poor prognosis. Our integrative analyses of transcriptome and proteome reveal distinctive molecular features of ccRCC with VTT, and yield the development of a prognostic classifier to facilitate ccRCC molecular subtyping and treatment. The RNA sequencing and mass spectrometry were performed in normal-tumor-thrombus tissue triples of five ccRCC patients. Statistical analysis, GO and KEGG enrichment analysis, and protein–protein interaction network construction were used to interpret the transcriptomic and proteomic data. A six-gene-based classifier was developed to predict patients’ survival using Cox regression, which was validated in an independent cohort. Transcriptomic analysis identified 1131 tumorigenesis-associated differentially expressed genes (DEGs) and 856 invasion-associated DEGs. Overexpression of transcription factor EGR2 in VTT indicated its important role in tumor invasion. Furthermore, proteomic analysis showed 597 tumorigenesis-associated differentially expressed proteins (DEPs) and 452 invasion-associated DEPs. The invasion-associated DEPs showed unique enrichment in DNA replication, lysine degradation, and PPAR signaling pathway. Integration of transcriptome and proteome reveals 142 tumorigenesis-associated proteins and 84 invasion-associated proteins displaying changes consistent with corresponding genes in transcriptomic profiling. Based on their different expression patterns among normal-tumor-thrombus triples, RAB25 and GGT5 were supposed to play a consistent role in both tumorigenesis and invasion processes, while SHMT2 and CADM4 might play the opposite roles in tumorigenesis and thrombus invasion. A prognostic classifier consisting of six DEGs (DEPTOR, DPEP1, NAT8, PLOD2, SLC7A5, SUSD2) performed satisfactorily in predicting survival of ccRCC patients (HR = 4.41, P

Background and aimsSystemic combinations have recently brought significant therapeutic benefits for advanced hepatocellular carcinoma (aHCC). To design the most effective combination regimens, a systematic review (PROSPERO ID: CRD42022321949) was conducted to evaluate the efficacy and safety of systemic combinations on aHCC.MethodsWe retrieved all the studies from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI) using the Medical Subject Headings (MeSH) terms until December 21, 2022. The effect indicators (hazard ratio [HR], relative risk [RR], and median) were pooled by a fixed- or random-effects model. A subgroup analysis was conducted according to types and specific therapies.ResultsIn total, 88 eligible studies were selected from 7249 potential records. Each kind of combination treatment (chemotherapy plus chemotherapy, targeted plus immune checkpoint inhibitor (ICI) therapy, targeted plus chemotherapy, and targeted plus targeted therapy) had a better objective response rate (ORR) in patients with aHCC, compared to the monotherapy mostly with sorafenib (RR: 1.57 [1.44–1.71]; I2 = 30%). Of those, targeted plus ICI therapy showed better therapeutic efficiency in overall survival (median: 15.02 [12.67–17.38]), progression-free survival (median: 7.08 [6.42–7.74]), and ORR (RR: 1.81 [1.55–2.13]), compared to the monotherapy. Specifically, Atezo plus Beva showed all those benefits. Our pooled result showed all the combinations had increased ≥3 Grade treatment-related adverse events (TrAEs), with an RR of 1.25 [95% CI: 1.15–1.36], compared to the monotherapy.ConclusionThe systemic combinations, especially targeted plus ICI therapy, including Atezo plus Beva, significantly improve clinical outcomes but increase side effects in patients with aHCC. Future trials should concentrate on improvement in therapeutic efficiency and reduction of toxicity of targeted plus ICI therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022321949.

Abstract Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS‐CoV‐2 infection via upregulating angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans‐activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS‐CoV‐2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon‐λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS‐CoV‐2 infection by boosting NR4A2‐induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS‐CoV‐2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

Abstract For a “Carbon Neutrality” society, electrochemical energy storage and conversion (EESC) devices are urgently needed to facilitate the smooth utilization of renewable and sustainable energy where the electrode materials and catalysts play a decisive role. However, the efficiency of the current trial‐and‐error research paradigm largely lags behind the imminent demands of EESC requiring increasingly improved performance. The emerged machine learning (ML), a subfield of artificial intelligence, is capable of evaluating and analyzing big data for hidden rules. In this regard, the relationships between the structure and performance of the key materials can be more efficiently revealed, which fundamentally revolutionizes the material research manner of the current EESC devices. In this review, the typical ML algorithms utilized in EESC development are first introduced. Then, focused attention has been paid to multiple aspects of applying ML to reshape the materials research for EESC. In addition to highlighting the emerging prospect, the challenges which are still hindering the further development of this emerging field are also discussed.

Background: Transplantation of bone marrow mesenchymal stem cells (BMSCs) has a promising therapeutic efficiency for varieties of disorders caused by ischemia or reperfusion impairment. It has been shown that BMSCs can mitigate intestinal ischemia/reperfusion (I/R) injuries, but the underlying mechanism is still unclear. This study aimed at investigating the efficacy of BMSCs on the immune function of intestinal mucosal microenvironment after I/R injuries. Methods: Twenty adult Sprague-Dawley rats were randomly assigned to a treatment or a control group. All the rats underwent superior mesenteric artery clamping and unclamping. In the treatment group, BMSCs were implanted into the intestine of ten rats by direct submucosal injection whereas the other ten rats in the control group were injected with the same volume of saline. On the fourth and seventh day after BMSCs transplantation, intestinal samples were examined for the CD4 (CD4-positive T-lymphocytes)/CD8 (CD8-positive T-lymphocytes) ratio of the bowel mucosa via flow cytometry, and for the level of Interleukin-2 (IL-2), Interleukin-4 (IL-4) and Interleukin-6 (IL-6) via ELISA. Paneth cell counts and Secretory Immunoglobulin A (SIgA) level were examined via immunohistochemical (IHC) analysis. Real time PCR (RT-PCR) was used to detect the expression levels of tumor necrosis factor-α (TNF-α) and trypsinogen (Serine 2) (PRSS2) genes. White blood cell (WBC) count was measured by manual counting under the microscope. Results: The CD4/CD8 ratio in the treatment group was significantly lower compared with that in the control group. The concentration of IL-2 and IL-6 was lower in the treatment group compared with the control group, while the level of IL-4 is the reverse between the two groups. The number of Paneth cells in intestinal mucosa increased significantly, while the level of SIgA in intestinal mucosa decreased significantly, after BMSCs transplantation. The gene expression levels of TNF-α and PRSS2 in intestinal mucosa of treatment group were significantly lower than those of control group. The WBC count in the treatment group was significantly lower than that in the control group. Conclusion: We identified immune-relevant molecular changes that may explain the mechanism of BMSCs transplantation efficacy in alleviating rat intestinal immune-barrier after I/R.

BackgroundClear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT) have poor prognosis. We aimed to reveal features of ccRCC with VTT and develop a urine-based prognostic classifier to predict ccRCC prognosis through integrative analyses of transcriptomic landscape and urinary signature.MethodsRNA sequencing was performed in five patients with ccRCC thrombus-tumor-normal tissue triples, while mass spectrometry was performed for urine samples from 12 ccRCC and 11 healthy controls. A urine-based classifier consisting of three proteins was developed to predict patients’ survival and validated in an independent cohort.ResultsTranscriptomic analysis identified 856 invasion-associated differentially expressed genes (DEGs). Furthermore, proteomic analysis showed 133 differentially expressed proteins (DEPs). Integration of transcriptomic landscape and urinary signature reveals 6 urinary detectable proteins (VSIG4, C3, GAL3ST1, TGFBI, AKR1C3, P4HB) displaying abundance changes consistent with corresponding genes in transcriptomic profiling. According to TCGA database, VSIG4, TGFBI, and P4HB were significantly overexpressed in patients with shorter survival and might be independent prognostic factors for ccRCC (all p

Abstract Background The long‐term trend in cancer death in a rapidly developing country provides information for cancer prophylaxis. Here, we aimed to identify the trends in cancer mortality in China during the 2004‐2018 period. Methods Using raw data from the national mortality surveillance system of China, we assessed the mortalities of all cancer and site‐specific cancers during the 2004‐2018 period. The participants were divided into three age groups: ≥65 years, 40‐64 years, and ≤39 years. Changing trends in cancer death by gender, residency, and tumor location were estimated using fitting joinpoint models to log‐transformed crude mortality rates (CMRs) and age‐standardized mortality rates (ASMRs). Results Cancer death accounted for 24% of all‐cause of death in China during 2014‐2018. The CMR of all cancer was 150.0 per 100,000 persons. Cancer was the leading cause of death in the population

Background: Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. Methods: We enrolled 193 SARS-CoV-2 infected subjects in Ningbo and Zhoushan, Zhejiang, China, from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and IgG against SARS-CoV-2 using colloidal gold-labeled and enzyme-linked immunosorbent assays. Results: Of those, 31 were asymptomatic SARS-CoV-2 carriers, 148 symptomatic COVID-19 patients, and 14 presymptomatic COVID-19 patients. Compared to symptomatic COVID-19 patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower level of C-reactive protein, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (7.5 vs. 25.5 days, P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic patients than presymptomatic patients (P = 0.003) and asymptomatic carriers (P = 0.004). Viral shedding duration was longer in presymptomatic COVID-19 patients than in asymptomatic carriers (48.0 vs. 24.0 days, P = 0.002). Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89.0% vs. 61.0%, P = 0.028). In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with comorbidities. Conclusion: Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity should be contributable to innate and adaptive cellular immunity rather than humoral immunity. The severity of COVID-19 is associated with older age and comorbidities in familial clustering cases.

Carbon dioxide electroreduction (CO2RR) with renewable energy is of great significance to realize carbon neutralization. Traditional electrolysis devices usually need an ion exchange membrane to eliminate the interference of oxygen generated on the anode. Herein, the novel CuO/CeO2 composite was facilely prepared by anchoring small CuO nanoparticles on the surface of CeO2 nanocubes. In addition, CuO(002) crystal planes were induced to grow on CeO2(200), which was preferable for CO2 adsorption and C-C bond formation. As the catalyst in a membrane-free cell for CO2RR, the Cu+ was stabilized due to strong interactions between copper and ceria to resist the reduction of negative potentials and the oxidation of oxygen from the counter electrode. As a result, a high Faradaic efficiency of 62.2% toward C2 products (ethylene and ethanol) was achieved for the first time in the membrane-free conditions. This work may set off a new upsurge to drive the industrial application of CO2RR through membrane-free electrocatalysis.

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P

Cancer development follows an evolutionary pattern of “mutation-selection-adaptation” detailed by Cancer Evolution and Development (Cancer Evo-Dev), a theory that represents a process of accumulating somatic mutations due to the imbalance between the mutation-promoting force and the mutation-repairing force and retro-differentiation of the mutant cells to cancer initiation cells in a chronic inflammatory microenvironment. The fragile histidine triad (FHIT) gene is a tumor suppressor gene whose expression is often reduced or inactivated in precancerous lesions during chronic inflammation or virus-induced replicative stress. Here, we summarize evidence regarding the mechanisms by which the FHIT is inactivated in cancer, including the loss of heterozygosity and the promoter methylation, and characterizes the role of the FHIT in bridging macroevolution and microevolution and in facilitating retro-differentiation during cancer evolution and development. It is suggested that decreased FHIT expression is involved in several critical steps of Cancer Evo-Dev. Future research needs to focus on the role and mechanisms of the FHIT in promoting the transformation of pre-cancerous lesions into cancer.

Overall water splitting becomes an important strategy for the generation of hydrogen and oxygen in today's needs of green energy. Therefore, it is important to develop bifunctional electrocatalysts with cheap and high-efficient characteristics. However, traditional bifunctional catalysts usually exhibit high overpotential and poor stability during both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, we synthesized several kinds of CoP nanorod catalysts through a facile hydrothermal method and subsequent thermal phosphorization process. The as-obtained CoP-1.5 product showed an overpotential of 58 mV for HER at 10 mA cm−2 and 284 mV for OER at 50 mV cm−2 in 1 M KOH. Moreover, the bifunctional catalyst, delivered a cell voltage of 1.66 V at 50 mA cm−2.

We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) mutations increase the occurrence of hepatocellular carcinoma (HCC) and identify novel putative therapeutic targets. Wild-type HBx (WT-HBx) and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; and Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into Sleeping Beauty (SB) mouse models. The HCC incidence was higher in the M3-HBx- and Ct-HBx-injected SB mice. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. Ectopic expression of M3-HBx and Ct-HBx significantly increased proliferation and S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors by cDNA microarray analysis. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of SB mice. Silencing PAI1 attenuated the effects of M3-HBx and Ct-HBx on the growth of HepG2 and HeLa cells. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a prognostic biomarker and therapeutic target in HBV-related HCC.

Abstract Background Recurrence is the major cause of hepatocellular carcinoma (HCC) death. We aimed to identify circular RNA (circRNA) with predictive and therapeutic value for recurrent HCC. Methods Tissue samples from recurrent and non‐recurrent HCC patients were subjected to circRNA sequencing and transcriptome sequencing. circKCNN2 was identified through multi‐omics analyses. The effects of circKCNN2 on HCC were evaluated in cells, animals, database of The Cancer Genome Atlas, and a cohort with 130 HCC patients. circRNA precipitation, chromatin immunoprecipitation assay, RNA pull‐down, luciferase assay, and cell experiments were applied to evaluate the interaction of circKCNN2 with miRNAs and proteins. The association between circKCNN2 and the therapeutic effect of lenvatinib was investigated in HCC cell lines and HCC tissue‐derived organoids. Results The expression of circKCNN2 was downregulated in HCC tissues and predicted a favorable overall survival and recurrence‐free survival. The expression of circKCNN2 was positively correlated with the parental gene, potassium calcium‐activated channel subfamily N member (KCNN2). Nuclear transcription factor Y subunit alpha (NFYA) was proven to inhibit the promoter activity of KCNN2, downregulate the expression of KCNN2 and circKCNN2, and predict an unfavorable recurrence‐free survival. Ectopic expression of circKCNN2 inhibited HCC cell proliferation, colony formation, migration, and tumor formation in a mouse model. miR‐520c‐3p sponged by circKCNN2 could reverse the inhibitory effect of circKCNN2 on HCC cells and down‐regulate the expression of methyl‐DNA‐binding domain protein 2 (MBD2). The intratumoral expression of MBD2 predicted a favorable recurrence‐free survival. circKCNN2 down‐regulated the expression of fibroblast growth factor receptor 4 (FGFR4), which can be reversed by miR‐520c‐3p and knockdown of MBD2. Lenvatinib inhibited the expression of FGFR4 and upregulated the expression of circKCNN2 and MBD2. Ectopic expression of circKCNN2 in HCC cells enhanced the therapeutic effect of lenvatinib. However, the high inherent level of circKCNN2 in HCC cells was associated with lenvatinib resistance. Conclusions circKCNN2, transcriptionally repressed by NFYA, suppresses HCC recurrence via the miR‐520c‐3p/MBD2 axis. Inherent level of circKCNN2 in HCC cells predisposes anti‐tumor effect of lenvatinib possibly because both circKCNN2 and lenvatinib repress the expression of FGFR4. circKCNN2 may be a promising predictive biomarker and therapeutic agent for HCC recurrence.

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality worldwide. The effect of socioeconomic factors on cause-specific mortality and burden of CVD is rarely evaluated in low- and middle-income countries, especially in a rapidly changing society. Methods Original data were derived from the vital registration system in Yangpu, a representative, population-stable district of urban Shanghai, China, during 1974–2015. Temporal trends for the mortality rates and burden of CVD during 1974–2015 were evaluated using Joinpoint Regression Software. The burden was evaluated using age-standardized person years of life loss per 100,000 persons (SPYLLs). Age-sex-specific CVD mortality rates were predicted by using age-period-cohort Poisson regression model. Results A total of 101,822 CVD death occurred during 1974–2015, accounting for 36.95% of total death. Hemorrhagic stroke, ischemic heart disease, and ischemic stroke were the 3 leading causes of CVD death. The age-standardized CVD mortality decreased from 144.5/100,000 to 100.7/100,000 in the residents (average annual percentage change [AAPC] -1.0, 95% confidence interval [CI] -1.7 to − 0.2), which was mainly contributed by women (AAPC -1.3, 95% CI − 2.0 to − 0.7), not by men. Hemorrhagic stroke, the major CVD death in the mid-aged population, decreased dramatically after 1991. The crude mortality of ischemic heart disease kept increasing but its age-adjusted mortality decreased continually after 1997. SPYLLs of CVD death increased from 1974 to 1986 (AAPC 2.1, 95% CI 0.4 to 3.8) and decreased after 1986 (AAPC 1.8, 95% CI − 2.3 to − 1.3). These changes were in concert with the implementation of policies including extended medical insurance coverage, pollution control, active prophylaxis of CVD including lifestyle promotion, and national health programs. The mortality of CVD increased in those born during 1937–1945, a period of the Japanese military occupation, and during 1958–1965, a period including the Chinese Famine. Sequelae of CVD and ischemic heart disease are predicted to be the leading causes of CVD death in 2029. Conclusions Exposure to serious malnutrition in early life might increase CVD mortality in later life. Improvements in medical services, pollution control, and lifestyle could decrease CVD death. New strategy is needed to prevent the aging-related CVD death and burden in the future.

ABSTRACT: Background: The corresponding author's experience and recent methods employed in autologous costal cartilage grafts combined with expanded polytetrafluoroethylene (ePTFE) in Asian rhinoplasty were presented in this study. Objectives: The purpose of this study was to assess the outcomes of rhinoplasty performed on patients using autogenous costal cartilage grafts combined with an ePTFE implant. Methods: Seventy-five rhinoplasty cases with autologous costal cartilage grafts and an ePTFE implant were retrospectively reviewed. Graft types, complications associated with the graft itself or graft harvesting, surgical outcomes, and patient satisfaction were assessed. Results: The mean follow-up time post-operation was 13.5 months. A total of 42/75 patients underwent revision surgeries. Graft-related complications were found in 8% of cases, including two warped graft and four infection cases. Three individuals with infections had mild graft resorption. One patient with an infection removed the implant. Graft exposure, mobility, and substantial resorption were not recorded. A total of two cases underwent revision procedures for infection and perforation, respectively. Chest incision lengths for graft harvesting averaged 2.1 cm. No pneumothorax or significant donor-site pain was found. Donor-site scars were negligible, although two cases had hypertrophic chest scars. In general, functional and esthetic outcomes were mostly satisfactory among the assessed patients. Conclusions: Rhinoplasty using autologous rib cartilage provides adequate support and sufficient cartilage amounts for correcting nasal contouring. Meanwhile, ePTFE alone for nasal dorsum augmentation safely achieves satisfactory outcomes. Rib cartilage rhinoplasty performed by an experienced surgeon yields excellent, long-lasting results with minimal risk; however, the potential for infection should be considered following revision surgery.

Objective Anastomotic leakage (AL) is the most serious postoperative complication following anterior resection for rectal cancer. We aimed to investigate the efficacy of active drainage for the management of AL. Methods This was a retrospective study using information from a database of patients who underwent colorectal resection without a defunctioning ileostomy at our center between September 2013 and January 2021. We identified 122 cases with definitive AL who did not require revision emergent laparotomy. Among these patients, we evaluated those who received active drainage to replace the original passive drainage. Results There were 62 cases in the active drainage group and 60 cases in the passive drainage group. The active drainage group had a shorter mean AL spontaneous resolution time (26.9 ± 3.3 vs. 32.2 ± 4.8 days) and lower average hospitalization costs (82,680.6 vs. 92,299.3 renminbi (RMB)) compared with the passive drainage group, respectively. Moreover, seven patients in the passive drainage group subsequently underwent diverting stoma to resolve the Al, while all ALs resolved spontaneously after replacing the passive drainage with active drainage. Conclusions Our study suggests that active drainage may accelerate the spontaneous resolution of AL.

Chronic inflammation is a prerequisite for the development of cancers. Here, we present the framework of a novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev) based on the current understanding of inflammation-related carcinogenesis, especially hepatocarcinogenesis induced by chronic infection with hepatitis B virus. The interaction between genetic predispositions and environmental exposures, such as viral infection, maintains chronic non-resolving inflammation. Pollution, metabolic syndrome, physical inactivity, ageing, and adverse psychosocial exposure also increase the risk of cancer via inducing chronic low-grade smoldering inflammation. Under the microenvironment of non-resolving inflammation, pro-inflammatory factors facilitate the generation of somatic mutations and viral mutations by inducing the imbalance between the mutagenic forces such as cytidine deaminases and mutation-correcting forces including uracil–DNA glycosylase. Most cells with somatic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of mutated cells survive, adapt to the hostile environment, retro-differentiate, and function as cancer-initiating cells via altering signaling pathways. These cancer-initiating cells acquire stem-ness, reprogram metabolic patterns, and affect the microenvironment. The carcinogenic process follows the law of “mutation-selection-adaptation”. Chronic physical activity reduces the levels of inflammation via upregulating the activity and numbers of NK cells and lymphocytes and lengthening leukocyte telomere; downregulating proinflammatory cytokines including interleukin-6 and senescent lymphocytes especially in aged population. Anti-inflammation medication reduces the occurrence and recurrence of cancers. Targeting cancer stemness signaling pathways might lead to cancer eradication. Cancer Evo-Dev not only helps understand the mechanisms by which inflammation promotes the development of cancers, but also lays the foundation for effective prophylaxis and targeted therapy of various cancers.

Objectives: Cancer is well-known as a collection of diseases of uncontrolled proliferation of cells caused by mutated genes which are generated by external or internal factors. As the mechanisms of cancer have been constantly revealed, including cell cycle, proliferation, apoptosis and so on, a series of new emerging anti-cancer drugs acting on each stage have also been developed. It is worth noting that natural products are one of the important sources for the development of anti-cancer drugs. To the best of our knowledge, there is not any database summarizing the relationships between natural products, compounds, molecular mechanisms, and cancer types.Materials and methods: Based upon published literatures and other sources, we have constructed an anti-cancer natural product database (ACNPD) (http://www.acnpd-fu.com/). The database currently contains 521 compounds, which specifically refer to natural compounds derived from traditional Chinese medicine plants (derivatives are not considered herein). And, it includes 1,593 molecular mechanisms/signaling pathways, covering 10 common cancer types, such as breast cancer, lung cancer and cervical cancer.Results: Integrating existing data sources, we have obtained a large amount of information on natural anti-cancer products, including herbal sources, regulatory targets and signaling pathways. ACNPD is a valuable online resource that illustrates the complex pharmacological relationship between natural products and human cancers.Conclusion: In summary, ACNPD is crucial for better understanding of the relationships between traditional Chinese medicine (TCM) and cancer, which is not only conducive to expand the influence of TCM, but help to find more new anti-cancer drugs in the future.

BackgroundCancer becomes the leading cause of premature death in China. Primary objective of this study was to determine the major risk factors especially glucose intolerance for cancer prophylaxis.MethodsA cluster sampling method was applied to enroll 10,657 community-based adults aged 15-92 years in Shanghai, China in 2013. A structured questionnaire and physical examination were applied in baseline survey. Prediabetes was diagnosed using 75-g oral glucose tolerance test. After excluding 1433 subjects including 224 diagnosed with cancer before and 1 year after baseline survey, the remaining 9,224 subjects were followed-up to December 31, 2020.ResultsA total of 502 new cancer cases were diagnosed. The cancer incidence was 10.29, 9.20, and 5.95/1,000 person-years in diabetes patients, those with prediabetes, and healthy participants, respectively (p

This study aimed to elucidate the effects and underlying mechanisms of hepatitis B virus (HBV) preS mutations on hepatocarcinogenesis. The effect of the preS mutations on hepatocellular carcinoma (HCC) occurrence was evaluated using a prospective cohort study with 2114 HBV-infected patients, of whom 612 received antiviral treatments. The oncogenic functions of HBV preS mutations were investigated using cancer cell lines and Sleeping Beauty (SB) mouse models. RNA-sequencing and microarray were applied to identify key molecules involved in the mutant-induced carcinogenesis. Combo mutations G2950A/G2951A/A2962G/C2964A and C3116T/T31C significantly increased HCC risk in patients without antiviral treatment, whereas the preS2 deletion significantly increased HCC risk in patients with antiviral treatment. In SB mice, the preS1/preS2/S mutants induced a higher rate of tumor and higher serum levels of inflammatory cytokines than did wild-type counterpart. The preS1/preS2/S mutants induced altered gene expression profiles in the inflammation- and metabolism-related pathways, activated pathways of endoplasmic reticulum (ER) stress, affected the response to hypoxia, and upregulated the protein level of STAT3. Inhibiting the STAT3 pathway attenuated the effects of the preS1/preS2/S mutants on cell proliferation. G2950A/G2951A/A2962G/C2964A, C3116T/T31C, and preS2 deletion promote hepatocarcinogenesis via inducing ER stress, metabolism alteration, and STAT3 pathways, which might be translated into HCC prophylaxis.

Abstract Background We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. Methods The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. Results FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P

S100A4 is particularly associated with the progression and metastasis of numerous human malignancies. This study was designed to examine the clinicopathologic significance of S100A4 in gastrointestinal stromal tumor (GISTs). The level of OPNS100A4 expression in a large cohort of resectable GISTs was evaluated with immunohistochemistry. Its correlation with the clinicopathologic parameters of patients with resectable GISTs was analyzed. A survival analysis was performed to evaluate the prognostic significance of S100A4 expression using Kaplan-Meier method. Results: In 108 patients with resectable GISTs, the most high-risk GISTs had a strong level of S100A4 expression. Strong S100A4 expression was significantly associated with tumor size, mitosis, and recurrence, but not gender and age. Patients with weak S100A4 expression had a relatively longer disease-free survival compared to patients with strong S100A4 expression.Therefore, S100A4 expression is a putative marker for tumor progression and an adverse prognosis in GISTs.

In this paper, a new method of annular platform-supported headspace liquid-phase microextraction (LPME) was designed using ionic liquid as an extraction solvent, wherein extraction stability and efficiency were improved by adding an annular platform inside the extraction bottle. The ionic liquid 1-silicyl-3-benzylimidazolehexafluorophosphate was first synthesized and proved to be an excellent extraction solvent. Coupled with liquid chromatography, the proposed method was employed to analysis of polycyclic aromatic hydrocarbons (PAHs) in water and optimized in aspects of extraction temperature, extraction solvent volume, extraction time, pH, stirring rate, and salt effect of solution. The results indicated that this method showed good linearity (R2 > 0.995) within 0.5 µg·L−1 to 1000 µg·L−1 for PAHs. The method was more suitable for extraction of volatile PAHs, with recoveries from 65.0% to 102% and quantification limits from 0.01 to 0.05 µg·L−1. It has been successfully applied for detection of PAHs in seawater samples.

OBJECTIVES: We aimed to determine the associations of genetic polymorphisms of excision repair cross-complementation group 1 (ERCC1) rs11615, xeroderma pigmentosum group D (XPD/ERCC2) rs13181, X-ray repair cross complementing group 1 (XRCC1) rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1) rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1) rs1045642 with response to chemotherapy and survival of non-small cell lung cancer (NSCLC) in a Chinese population. MATERIALS AND METHODS: A total of 352 NSCLC patients were enrolled to evaluate the associations of the six SNPs with response to chemotherapy and overall survival. Logistic regressions were applied to test the associations of genetic polymorphisms with response to chemotherapy in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and 156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test, respectively. Multivariate Cox proportional hazards model was performed to determine the factors independently associated with NSCLC prognosis. RESULTS: BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95% CI = 0.204-0.794, p = 0.008) and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95% CI = 0.244-0.934, p = 0.030) were associated with a better response to chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1 rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR = 0.617, 95% CI = 0.402-0.948, p = 0.028) in advanced NSCLC patients, and the association was still significant after the adjustment for covariates. Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P = 0.020) and smoking (p = 0.037) were associated with increased risks of death in early stage NSCLC patients after surgery. CONCLUSIONS: Polymorphisms of genes in DNA repair pathway and MDR1 could contribute to chemotherapy response and survival of patients with NSCLC.

BACKGROUND: Disaster is a serious public health issue. Health professionals and community residents are main players in disaster responses but their knowledge levels of disaster medicine are not readily available. This study aimed to evaluate knowledge levels and training needs of disaster medicine among potential disaster responders and presented a necessity to popularize disaster medicine education. METHODS: A self-reporting questionnaire survey on knowledge level and training needs of disaster medicine was conducted in Shanghai, China, in 2012. A total of randomly selected 547 health professionals, 456 medical students, and 1,526 local residents provided intact information. The total response rate was 93.7%. RESULTS: Overall, 1.3% of these participants have received systematic disaster medicine training. News media (87.1%) was the most common channel to acquire disaster medicine knowledge. Although health professionals were more knowledgeable than community residents, their knowledge structure of disaster medicine was not intact. Medical teachers were more knowledgeable than medical practitioners and health administrators (p = 0.002). Clinicians performed better than public health physicians (p