Global burden of hip fracture: The Global Burden of Disease Study.

This study is the first to measure global burden of hip fracture in patients aged 55 years and older across 204 countries and territories from 1990 to 2019. Our study further proved that the global burden of hip fracture is still large. Hip fractures among males are perhaps underestimated, and older adults should be given more attention. PURPOSE: Hip fracture is a tremendous universal public health challenge, but no updated comprehensive and comparable assessment of hip fracture incidence and burden exists for most of the world in older adults. METHODS: Using data from the Global Burden of Diseases (GBD) 2019, we estimated the number and rates of the incidence, prevalence, and years lived with disability (YLD) of hip fracture across 204 countries and territories in patients aged 55 years and older from 1990 to 2019. RESULTS: In 2019, the incidence, prevalence, and YLDs rates of hip fracture in patients aged 55 years and older were 681.35 (95% UI 508.36-892.27) per 100000 population, 1191.39 (95% UI 1083.80-1301.52) per 100000 population, and 130.78 (95% UI 92.26-175.30) per 100000 population. During the three decades, the incidence among people aged below 60 years showed a downward trend, whereas it showed a rapid upward trend among older adults. All the numbers and rates of hip fractures among females were higher than those among males and increased with age, with the highest number and rate in the highest age group. Notably, the male to female ratio of the incidence for people aged over 55 years increased from 0.577 in 1990 to 0.612 in 2019. Falls were the leading cause among both sexes and in all age groups. CONCLUSIONS: The incidence and the number of hip fractures among patients aged 55 years and older increased over the past three decades, indicating that the global burden of hip fracture is still large. Hip fractures among males are perhaps underestimated, and older adults should be given more attention.

Non-targeted mass spectrometry and feature-based molecular networking for determination of branched fatty acid esters of hydroxy fatty acids in milk.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) represent trace lipids with significant natural biological functions. While exogenous FAHFAs have been extensively studied, research on FAHFAs in milk remains limited, constraining our grasp of their nutritional roles. This study introduces a non-targeted mass spectrometry approach combined with chemical networking of spectral fragmentation patterns to uncover FAHFAs. Through meticulous sample handling and comparisons of various data acquisition and processing modes, we validate the method's superiority, identifying twice as many FAHFAs compared to alternative techniques. This validated method was then applied to different milk samples, revealing 45 chemical signals associated with known and potential FAHFAs, alongside findings of 66 ceramide/hexosylceramide (Cer/HexCer), 48 phosphatidyl ethanolamine/lyso phosphatidyl ethanolamine (PE/LPE), 21 phosphatidylcholine/lysophosphatidylcholine (PC/LPC), 16 phosphatidylinositol (PI), 7 phosphatidylserine (PS), and 11 sphingomyelin (SM) compounds. This study expands our understanding of the FAHFA family in milk and provides a fast and convenient method for identifying FAHFAs.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.

Pan-Genomic Analysis Identifies the Chinese Strain as a New Subspecies of Xanthomonas fragariae.

Xanthomonas fragariae is classified as a quarantine pathogen by the European and Mediterranean Plant Protection Organization. It commonly induces typical angular leaf spot (ALS) symptoms in strawberry leaves. X. fragariae strains from China (YL19, SHAQP01, and YLX21) exhibit ALS symptoms in leaves and more severe symptoms of dry cavity rot in strawberry crowns. Conversely, strains from other countries do not cause severe dry cavity rot symptoms in strawberries. After employing multilocus sequence analysis (MLSA), average nucleotide identity (ANI), and amino acid identity (AAI), we determined that Chinese strains of X. fragariae are genetically distinct from other strains and can be considered a new subspecies. Subsequent analysis of 63 X. fragariae genomes published at NCBI using IPGA and EDGAR3.0 revealed the pan-genomic profile, with 1,680 shared genes present in all 63 strains, including 71 virulence-related genes. Additionally, we identified 123 genes exclusive to all the Chinese strains, encompassing 12 virulence-related genes. The qRT-PCR analysis demonstrated that the expression of XopD, XopG1, CE8, GT2, and GH121 out of 12 virulence-related genes of Chinese strains (YL19) exhibited a constant increase in the early stages (6, 24, 54, and 96 hours postinoculation [hpi]) of strawberry leaf infected by YL19. So, the presence of XopD, XopG1, CE8, GT2, and GH121 in Chinese strains may play important roles in the early infection process of Chinese strains. These findings offer novel insights into comprehending the population structure and variation in the pathogenic capacity of X. fragariae.

Structural and functional properties of whey protein isolate-inulin conjugates prepared with ultrasound or wet heating method.

BACKGROUND: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined. RESULTS: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), new C-N bonds were formed in Fourier-transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h. CONCLUSION: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.

Measurable residual disease detected by flow cytometry independently predicts prognoses of NPM1-mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity.

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1ß, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

Monomethyl branched-chain fatty acids-a pearl dropped in the ocean.

As an emerging group of bioactive fatty acids, monomethyl branched-chain fatty acids (mmBCFAs) have sparked the interest of many researchers both domestically and internationally. In addition to documenting the importance of mmBCFAs for growth and development, there is increasing evidence that mmBCFAs are highly correlated with obesity and insulin resistance. According to previous pharmacological investigations, mmBCFAs also exhibit anti-inflammatory effects and anticancer properties. This review summarized the distribution of mmBCFAs, which are widely found in dairy products, ruminants, fish, and fermented foods. Besides, we discuss the biosynthesis pathway in different species and detection methods of mmBCFAs. With the hope to unveil their mechanisms of action, we recapitulated detailed the nutrition and health benefits of mmBCFAs. Furthermore, this study provides a thorough, critical overview of the current state of the art, upcoming difficulties, and trends in mmBCFAs.

The metabolic syndrome and its components as prognostic factors in colorectal cancer: A meta-analysis and systematic review.

BACKGROUND AND AIM: Metabolic syndrome (MetS) increases the risk of colorectal cancer (CRC), and the impact of MetS on CRC prognosis remains controversial after the diagnosis of CRC has been established. This study aimed to explore the impact of the individual components and synergies of MetS on the prognosis of patients with CRC. METHODS: We searched articles published before August 3, 2022, in four databases, including PubMed, Embase, Cochrane Library, and ScienceDirect. The random-effects model inverse variance method was used to estimate the summarized effect size. RESULTS: Patients with CRC with MetS were 1.342 times more likely to experience all-cause mortality than those without MetS, and the 95% confidence interval (CI) of hazard ratio (HR) was 1.107-1.627 (P = 0.003). CRC-specific mortality in patients with CRC with MetS was 2.122 times higher than in those without MetS, and the 95% CI of HR was 1.080-4.173 (P = 0.029). CRC-specific mortality exhibited an increasing trend of risk with increased metabolic risk factors. The HR of CRC-specific mortality for one, two, and three metabolic risk factors was 1.206 (95% CI, 1.034-1.407; P = 0.017), 1.881 (95% CI, 1.253-2.824; P = 0.002), and 2.327 (95% CI, 1.262-4.291; P = 0.007), respectively. CONCLUSIONS: Metabolic syndrome increased all-cause and CRC-specific mortality in patients with CRC. As a single component of MetS, diabetes mellitus increased overall mortality in patients with CRC, while obesity increased CRC-specific mortality in patients with CRC, with a significant difference from non-MetS. Moreover, the risk of CRC-specific mortality increased with increasing number of metabolic risk factors.

Higher Prevalence of Generalized Pustular Psoriasis in Asia? A Population-Based Study Using Claim Data in China and a Systematic Review.

BACKGROUND: Few studies have reported the burden of generalized pustular psoriasis (GPP), a severe and potentially life-threatening skin disease, especially at a national level. OBJECTIVES: The aim of this study is to estimate the nationwide burden of GPP in China and make a systemic review of the published data. METHODS: We conducted a population-based study using Urban Basic Medical Insurance in China from 2012 to 2016. GPP cases were identified by primary diagnoses including the international classification of Diseases codes (ICD-10: L40.1 and ICD-9: 694.3). A systematic review was conducted using relevant databases up to January 2022. RESULTS: The crude prevalence and incidence of GPP in 2016 were 1.403 (95% confidence interval [CI]: 1.115-1.691) and 0.629 (95% CI: 0.483-0.775) per 100,000 person-years, respectively. The rates were higher in males than in females for both prevalence (1.429 vs. 1.135) and incidence (0.635 vs. 0.520). The prevalence and incidence showed a bimodal age distribution, with the first peak occurring in the 0- to 3-year age-group and the second peak occurring in the 30- to 39-year age-group. The per capita total cost per year for 1 patient with GPP was 609.26 (± 45.77) US dollars. Seven studies were identified in a systematic review, according to which the prevalence (per 100,000) of GPP tended to be higher in Asian countries (0.746-8.178 in Japan and 12.230 in Korea) than in France (0.176), Sweden (6.25), and Brazil (0.7). CONCLUSIONS: This is the largest study concerning the disease burden of GPP, and in this study, the prevalence seemed to be higher in Asia. Although the direct economic burden of GPP did not seem high during the study period, the future usage of biologics and the humanistic burden should also be considered for policy-related decision-making.

Genipin Attenuates Sepsis-Induced Splenocyte Apoptosis via the Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.

Forsythiaside A Alleviates Lipopolysaccharide-Induced Acute Liver Injury through Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

The liver is the primary site of inflammation caused by bacterial endotoxins in sepsis, and septic acute liver injury (SALI) is usually associated with poor outcomes in sepsis. Forsythiaside A (FTA), an active constituent of Forsythia suspensa, has been reported to have anti-inflammatory properties, antioxidant properties, and protective properties against neuroinflammation, sepsis, and edema. Therefore, the purpose of the present study was to examine FTA's potential effects on lipopolysaccharide (LPS)-induced SALI in mice. Our results indicated that pretreatment with FTA significantly attenuated aspartate aminotransferase (AST) and aminoleucine transferase (ALT) levels in plasma, ameliorated histopathological damage, inhibited hepatocyte apoptosis, diminished the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the liver from mice exposed to LPS. Furthermore, our data showed that the administration of LPS resulted in robust endoplasmic reticulum (ER) stress response, as evidenced by glucose-regulated protein 78 (GRP78) upregulation, phosphorylated-protein kinase R-like ER kinase (p-PERK) activation, elF2α phosphorylation, and activating transcription factor 4 (ATF4) and CHOP overexpression in the liver. This, in turn, led to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, including the cleavage of caspase-1, secretion of IL-1ß, and pyroptotic cell death in the liver specimens. Importantly, the ER stress response induced by the LPS challenge was blocked by FTA administration. Correspondingly, NLRP3 inflammasome activation was significantly ameliorated by the pretreatment with FTA. Thus, we demonstrated that FTA pretreatment could protect mice from LPS-induced SALI, and its protective effects were possibly mediated by inhibiting ER stress response and subsequent NLRP3 inflammasome activation.

Changes in the Microbiota and their Roles in Patients with Type 2 Diabetes Mellitus.

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabetic subjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

Global burden of influenza lower respiratory tract infections in older people from 1990 to 2019.

BACKGROUND: Infections with influenza viruses cause severe illness, substantial number of hospitalization and death, especially in older adults. However, few studies have focused on the burden of influenza lower respiratory tract infections (LRTIs) solely in older adults, particularly in low-resource settings. AIMS: We aimed to estimate the mortality and DALYs of influenza LRTIs for people aged 55 years and older in 204 countries and territories from 1990 to 2019. METHODS: The Global Burden of Disease (GBD) 2019 study was used to obtain data on mortality and DALYs of influenza LRTIs at the global, regional, and country levels. RESULTS: In 2019, the global rates for mortality and DALYs of influenza LRTIs were 6.46 per 100,000 [95% uncertainty interval (UI): 2.37-12.62] and 97.39 per 100,000 (95% UI: 34.70-187.03). Although the rates for mortality and DALYs in people aged 55 years and older decreased from 1990 to 2019, the absolute numbers for both increased by 85.84% and 66.56%, respectively. Both the absolute numbers and rates of deaths and DALYs of influenza LRTIs were higher in male than in female in all age groups. Although low-socio-demographic index (SDI) regions experienced the largest declines for the rates of mortality and DALYs of influenza LRTIs over the past three decades, they still had the highest rates for mortality and DALYs in all age groups. Moreover, the absolute numbers and rates of deaths and DALYs of influenza LRTIs showed an increasing trend with age, reaching the peak in the people over 85 years old. DISCUSSION: Burden of influenza LRTIs in older adults is still high and could continue to grow along with global aging. CONCLUSION: Efforts to improve vaccination for influenza are needed for preparedness of another influenza pandemic, especially in low-SDI regions.

Isolation, purification, and mass spectrometry identification of the enzyme involved in citrus flavor (+)-valencene biotransformation to (+)-nootkatone by Yarrowia lipolytica.

BACKGROUND: (+)-Nootkatone is a highly valuable sesquiterpene compound that can be used as an aromatic in the food industry because of its grapefruit flavor and low sensory threshold. The unconventional yeast Yarrowia lipolytica has many unique physical and chemical properties, metabolic characteristics, and genetic structure, which has aroused the interest of researchers. Previous research showed that Y. lipolytica possesses the ability to transform the sesquiterpene (+)-valencene to (+)-nootkatone. The aim of this study was to isolate, purify, and identify the enzyme involved in the (+)-valencene bioconversion to (+)-nootkatone by Y. lipolytica. RESULTS: In this study, ultrasonic-assisted extraction, ammonium sulfate precipitation, anion-exchange chromatography, and gel-filtration chromatography were used to separate and purify the enzyme involved in the (+)-valencene bioconversion by Y. lipolytica. The protein was identified as aldehyde dehydrogenase (ALDH) (gene0658) using sodium dodecyl sulfate polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry analysis. The ALDH had the highest activity when the pH value was 6.0 and the temperature was 30 °C. The activity of ALDH was significantly stimulated by ferrous ions and inhibited by barium, calcium, and magnesium ions. CONCLUSION: This is the first time that ALDH was found to participate in (+)-valencene biotransformation by Y. lipolytica. It may be involved in regulating the microbial transformation of (+)-valencene to (+)-nootkatone through redox characteristics. This study provides a theoretical basis and reference for the biological synthesis of citrus flavor (+)-nootkatone. © 2023 Society of Chemical Industry.

Effect of different ways of ingesting orange essential oil on blood immune index and intestinal microflora in mice.

BACKGROUND: Studies have found that the addition of plant essential oils to feed had a positive effect on intestinal microflora and immunity in mice. However, the effect of different ways of ingestion of orange essential oil on mice has seldom been reported. In the present study, we investigated the effects of ingestion of orange essential oil by gavage, sniffing and feeding on intestinal microflora and immunity in mice. RESULTS: The results obtained showed that a low concentration of essential oil feeding significantly increased the spleen index of mice (P < 0.05). The effect of different ways of ingestion on the thymus index, immunoglobulin G and immunoglobulin M of mice was not significant (P > 0.05). High and medium concentrations of essential oil feeding increased the level of interleukin-2 in mice (P < 0.05). H+ K+ -ATPase activity was significantly increased in mice fed with gavage and different concentrations of essential oil feed compared to the control group (P < 0.05). The analysis of the results of the microflora in the cecum and colon of mice indicated that the medium concentration of essential oil feeding group and the sniffing group significantly changed the structure of the flora and increased the diversity of the intestinal microflora. All three essential oil ingestion methods increased the abundance of Bacteroidetes and Lactobacillus in the intestine of mice. CONCLUSION: Compared with gavage and feeding, sniffing had a significant effect on immunoglobulins in mice. All the three ingestion methods could affect the intestinal microflora of mice and increase the abundance of Lactobacillus. © 2022 Society of Chemical Industry.

[Meta-analysis of the relationship between maternal arsenic exposure and preterm birth].

OBJECTIVE: To systematic evaluate the association between maternal arsenic exposure and preterm birth. METHODS: A literature search was conducted through Pubmed, Web of Science, Embase, China Knowledge Network(CNKI), WanFang Data, Vip Chinese Journal Service Platform(VIP) with a time frame of November 2022 from the beginning of database construction. Meta-analysis of dichotomous variables was performed using Stata MP15 software, and a random or fixed effects model was chosen for the meta-analysis based on the heterogeneity result, with the ratio of ratios(OR) as the effect indicator; subgroup analysis was used to find characteristic changes; funnel plots were used to evaluate publication bias. RESULTS: A total of 15 papers with a sample size of(n=9 892 256 279), 10 prospective cohort studies, 3 retrospective cohort studies, and 2 cross-sectional studies, were included in 6 Chinese and 9 English papers. By Meta-analysis, the combined OR of preterm birth outcome was 1.06(95%CI 1.03-1.09); the result of subgroup analysis by exposure factors and region, the combined OR(95%CI) of hair, blood, urine, drinking water, and placenta were 0.97(0.56-1.69), 1.40(1.22-1.60), 1.04(0.93-1.17), 1.14(1.04-1.24) and 0.69(0.07-6.38). The combined OR(95%CI) were 1.17(1.04-1.31), 1.10(1.05-1.14), 0.69(0.07-6.38) and 1.17(1.01-1.36) for Asia, Americas, Europe and Africa, respectively. For subgroup analysis based on study type, the combined OR(95%CI) was 1.16(1.05-1.28), 1.01(1.01-1.02) and 1.65(0.73-3.74) for prospective cohort studies, retrospective cohort studies, and cross-sectional studies, respectively. CONCLUSION: Maternal arsenic exposure may contribute to the occurrence of preterm birth, and drinking water arsenic levels may be an important indicator for assessing human arsenic exposure and risk of causing preterm birth.

[Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments].

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

[Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/ß-catenin signaling pathway].

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/ß-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and ß-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and ß-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/ß-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.