"Treat-all" Strategy for Patients with Chronic Hepatitis B Virus Infection in China: Are We There Yet?

Chronic hepatitis B remains the primary cause of liver-related events in China. The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030. However, achieving this goal appears challenging due to the current low rates of diagnosis and treatment. The "Treat-all" strategy, which proposes treating all patients with detectable hepatitis B virus (HBV) DNA or even all patients with positive HBsAg, has been suggested to simplify anti-HBV treatment. In 2022, the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China, expanding antiviral indications and simplifying the treatment algorithm. According to this latest guideline, nearly 95% of patients with detectable HBV DNA are eligible for antiviral treatment. This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022) and to identify gaps in achieving the "Treat-all" strategy in China.

Invoking Interfacial Engineering Boosts Structural Stability Empowering Exceptional Cyclability of Ni-Rich Cathode.

The cycling stability of LiNi0.8Co0.1Mn0.1O2 under high voltages is hindered by the occurrence of hybrid anion- and cation-redox processes, leading to oxygen escape and uncontrolled phase collapse. In this study, an interfacial engineering strategy involving a straightforward mechanical ball milling and low-temperature calcination, employing a Se-doped and FeSe2&Fe2O3-modified approach is proposed to design a stable Ni-rich cathode. Se2- are selectively adsorbed within oxygen vacancies to form O─TM─Se bond, effectively stabilizing lattice oxygen, and preventing structural distortion. Simultaneously, the Se-NCM811//FeSe2//Fe2O3 self-assembled electric field is activated, improving interfacial charge transfer and coupling. Furthermore, FeSe2 accelerates Li+ diffusion and reacts with oxygen to form Fe2O3 and SeO2. The Fe2O3 coating mitigates hydrofluoric acid erosion and acts as an electrostatic shield layer, limiting the outward migration of oxygen anions. Impressively, the modified materials exhibit significantly improved electrochemical performance, with a capacity retention of 79.7% after 500 cycles at 1C under 4.5 V. Furthermore, it provides an extraordinary capacity retention of 94.6% in 3-4.25 V after 550 cycles in pouch-type full battery. This dual-modification approach demonstrates its feasibility and opens new perspective for the development of stable lithium-ion batteries operating at high voltages.

Diagnosis and treatment status of inoperable locally advanced breast cancer and the application value of inorganic nanomaterials.

Locally advanced breast cancer (LABC) is a heterogeneous group of breast cancer that accounts for 10-30% of breast cancer cases. Despite the ongoing development of current treatment methods, LABC remains a severe and complex public health concern around the world, thus prompting the urgent requirement for innovative diagnosis and treatment strategies. The primary treatment challenges are inoperable clinical status and ineffective local control methods. With the rapid advancement of nanotechnology, inorganic nanoparticles (INPs) exhibit a potential application prospect in diagnosing and treating breast cancer. Due to the unique inherent characteristics of INPs, different functions can be performed via appropriate modifications and constructions, thus making them suitable for different imaging technology strategies and treatment schemes. INPs can improve the efficacy of conventional local radiotherapy treatment. In the face of inoperable LABC, INPs have proposed new local therapeutic methods and fostered the evolution of novel strategies such as photothermal and photodynamic therapy, magnetothermal therapy, sonodynamic therapy, and multifunctional inorganic nanoplatform. This article reviews the advances of INPs in local accurate imaging and breast cancer treatment and offers insights to overcome the existing clinical difficulties in LABC management.

PbbHLH155 enhances iron deficiency tolerance in pear by directly activating PbFRO2 and PbbHLH38.

Iron (Fe) deficiency is a general stress for many horticulture crops, causing leaf chlorosis and stunted growth. The basic-helix-loop-helix (bHLH) transcription factor (TF) was reported to function in Fe absorption; however, the regulatory mechanism of bHLH genes on iron absorption remains largely unclear in pear. In this study, we found that PbbHLH155 was significantly induced by Fe deficiency. Overexpression of PbbHLH155 in Arabidopsis thaliana and pear calli significantly increases resistance to Fe deficiency. The PbbHLH155-overexpressed Arabidopsis lines exhibited greener leaf color, higher Fe content, stronger Fe chelate reductase (FCR) and root acidification activity. The PbbHLH155 knockout pear calli showed lower Fe content and weaker FCR activity. Interestingly, PbbHLH155 inhibited the expressions of PbFRO2 and PbbHLH38, which were positive regulators in Fe-deficiency responses (FDR). Furthermore, yeast one-hybrid (Y1H) and Dual-Luciferase Reporter (DLR) assays revealed that PbbHLH155 directly binds to the promoters of PbFRO2 and PbbHLH38, thus activating their expression. Overall, our results showed that PbbHLH155 directly promote the expression of PbFRO2 and PbbHLH38 to activate FCR activity for iron absorption. This study provided valuable information for pear breeding.

Transforming bio-waste lignin into amine functionalized carbon quantum dots for selective detection of trace Cu2+ in aqueous system.

Developing carbon quantum dots (CQDs) from bio-waste lignin for effectively detecting Cu2+ is of great significance for promoting the value-added utilization of lignin resources. However, the limited amount of surface-active groups and low quantum yield of lignin-based CQDs hinder their application in this regard. Herein, bio-waste lignin was converted into value-added amine functionalized CQDs using a facile two-step hydrothermal approach. The as-synthesized CQDs modified with amino groups exhibit bright green fluorescence, abundant surface functional groups, high water solubility and uniform particle size (3.9 nm). Systematic analysis demonstrates that the rich NH2 groups (~12.3 %) on the CQDs backbone improve their fluorescence properties (quantum yield increased from 3.4 % to 21.1 %) and specific detection ability for Cu2+. The developed NH2-CQDs serve as an efficient fluorescent probe, displaying high sensitivity and selectivity towards Cu2+ in aqueous system, with a detection limit of 2.42 µmol/L, which is lower than the maximum permitted amount of Cu2+ in drinking water (20 µmol/L). The detection mechanism of NH2-CQDs for Cu2+ is attributed to the synergy of static quenching and photo-induced electron transfer. This study provides a valuable reference for the synthesis of high-quality fluorescent CQDs from lignin resources and the effective detection of trace Cu2+ in aquatic environments.

Prevalence and clinical profiles of primary sclerosing cholangitis in China: Data from electronic medical records and systematic literature retrieval.

BACKGROUND & AIMS: Epidemiology of primary sclerosing cholangitis (PSC) is lacking in China. We aimed to estimate the period prevalence and depict the clinical features of PSC in China. METHODS: We identified and included PSC cases between 2000 and 2023 from two sources: electronic medical records (EMR) and systematical literature retrieval (SLR). The period prevalence of PSC was estimated by the multiplier method. Rate ratios (RRs) for PSC prevalence in relation to macroeconomic indicators were calculated by the negative binomial regression model. RESULTS: A total of 1358 PSC cases were retrieved from 299 hospitals (162 from EMR and 1196 from SLR). Males accounted for 55.7 % of the PSC cases and 25.7 % had concomitant inflammatory bowel disease (IBD). The estimated period prevalence of PSC from 2000 to 2023 was 2.36 (95 % CI: 1.82, 3.34) per 100,000. Males had a numerically higher PSC prevalence than females (2.56, 95 % CI: 1.97, 3.63 vs. 2.14, 95 % CI: 1.65, 3.04 per 100,000). The highest prevalence of PSC was in East China at 4.87 (95 % CI: 3.44, 7.18) per 100,000, followed by North China at 2.94 (95 % CI: 2.33, 3.74) per 100,000, and the lowest in South China at 0.92 (95 % CI: 0.66, 1.30) per 100,000. Regional per capita GDP (RR 1.65, 95 % CI: 1.03, 2.65) and healthcare expenditure (RR 1.94, 95 % CI: 1.13, 3.38) were identified to be associated with PSC prevalence. CONCLUSION: Our study showed the estimated PSC prevalence varied within China, but was generally lower than that in Western countries.

Stretchable Tb-Tb Distance Regulates the Piezofluorochromic Behavior of Chiral Tb(III)-MOF upon Compression.

Luminescent chiral Tb-MOF microcrystals with the Tb2(COO)4 subunit indicated strong green mechano-luminescence under compression. Furthermore, piezofluorochromic behavior in the diamond anvil cell was observed, with the intensity tendency of decreasing-increasing-decreasing and a shortened lifetime upon compression, due to the reversible stretchable Tb-Tb interactions. The Tb-Tb distance upon compression was refined through in situ high-pressure X-ray absorption spectra, which was consistent with the tendency of the piezofluorochromic intensity. In situ high-pressure UV-vis absorption spectra, Fourier transform infrared spectra, and powder X-ray diffraction demonstrated the full recovery of Tb-MOF after over 10 GPa compressions due to the semiflexible ligand. This work not only provided an ultrastable Tb-MOF but also illustrated the relationship of the piezofluorochromic behavior with the detailed structural transformation for the first time.

Agreements between GLIM using left calf circumference as criterion for reduced muscle mass and PG-SGA, and GLIM using ASMI for the diagnosis of malnutrition in gastric cancer patients.

OBJECTIVE: this study aimed to explore the agreements between the Global Leadership Initiative on Malnutrition (GLIM) using left calf circumference (CC) as criterion for reduced muscle mass and the Patient-Generated Subjective Global Assessment (PG-SGA), or GLIM using appendicular skeletal muscle index (ASMI) for the diagnosis of malnutrition in gastric cancer patients. METHODS: the Nutritional Risk Screening 2002 (NRS 2002) was used as nutritional risk screening. PG-SGA and GLIM were applied for malnutrition diagnosis. Agreements were evaluated by Kappa, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC). RESULTS: a total of 405 gastric cancer patients were included. The values of Kappa, sensitivity, specificity, PPV, NPV, accuracy and AUC were 0.463, 67.9 %, 87.3 %, 92.9 %, 52.8 %, 73.6 % and 0.776, and 0.496, 76.7 %, 78.0 %, 89.4 %, 57.9 %, 77.0 % and 0.773, respectively, between GLIM using CC with or without NRS 2002 and PG-SGA. All values of agreement were higher than 0.800 or 80.0 % between GLIM using left CC and GLIM using ASMI. CONCLUSION: the agreements were both acceptable between GLIM using left CC and PG-SGA, and GLIM using ASMI. Left calf circumference can be one of the credible references indicating a reduced muscle mass in patients with gastric cancer.

A predictive model for depression in Chinese middle-aged and elderly people with physical disabilities.

BACKGROUND: Middle-aged and older adults with physical disabilities exhibit more common and severe depressive symptoms than those without physical disabilities. Such symptoms can greatly affect the physical and mental health and life expectancy of middle-aged and older persons with disabilities. METHOD: This study selected 2015 and 2018 data from the China Longitudinal Study of Health and Retirement. After analyzing the effect of age on depression, we used whether middle-aged and older adults with physical disabilities were depressed as the dependent variable and included a total of 24 predictor variables, including demographic factors, health behaviors, physical functioning and socialization, as independent variables. The data were randomly divided into training and validation sets on a 7:3 basis. LASSO regression analysis combined with binary logistic regression analysis was performed in the training set to screen the predictor variables of the model. Construct models in the training set and perform model evaluation, model visualization and internal validation. Perform external validation of the model in the validation set. RESULT: A total of 1052 middle-aged and elderly persons with physical disabilities were included in this study, and the prevalence of depression in the elderly group > middle-aged group. Restricted triple spline indicated that age had different effects on depression in the middle-aged and elderly groups. LASSO regression analysis combined with binary logistic regression screened out Gender, Location of Residential Address, Shortsightedness, Hearing, Any possible helper in the future, Alcoholic in the Past Year, Difficulty with Using the Toilet, Difficulty with Preparing Hot Meals, and Unable to work due to disability constructed the Chinese Depression Prediction Model for Middle-aged and Older People with Physical Disabilities. The nomogram shows that living in a rural area, lack of assistance, difficulties with activities of daily living, alcohol abuse, visual and hearing impairments, unemployment and being female are risk factors for depression in middle-aged and older persons with physical disabilities. The area under the ROC curve for the model, internal validation and external validation were all greater than 0.70, the mean absolute error was less than 0.02, and the recall and precision were both greater than 0.65, indicating that the model performs well in terms of discriminability, accuracy and generalisation. The DCA curve and net gain curve of the model indicate that the model has high gain in predicting depression. CONCLUSION: In this study, we showed that being female, living in rural areas, having poor vision and/or hearing, lack of assistance from others, drinking alcohol, having difficulty using the restroom and preparing food, and being unable to work due to a disability were risk factors for depression among middle-aged and older adults with physical disabilities. We developed a depression prediction model to assess the likelihood of depression in Chinese middle-aged and older adults with physical disabilities based on the above risk factors, so that early identification, intervention, and treatment can be provided to middle-aged and older adults with physical disabilities who are at high risk of developing depression.

Experimental validation and comprehensive analysis of m6A methylation regulators in intervertebral disc degeneration subpopulation classification.

Intervertebral disc degeneration (IVDD) is one of the most prevalent causes of chronic low back pain. The role of m6A methylation modification in disc degeneration (IVDD) remains unclear. We investigated immune-related m6A methylation regulators as IVDD biomarkers through comprehensive analysis and experimental validation of m6A methylation regulators in disc degeneration. The training dataset was downloaded from the GEO database and analysed for differentially expressed m6A methylation regulators and immunological features, the differentially regulators were subsequently validated by a rat IVDD model and RT-qPCR. Further screening of key m6A methylation regulators based on machine learning and LASSO regression analysis. Thereafter, a predictive model based on key m6A methylation regulators was constructed for training sets, which was validated by validation set. IVDD patients were then clustered based on the expression of key m6A regulators, and the expression of key m6A regulators and immune infiltrates between clusters was investigated to determine immune markers in IVDD. Finally, we investigated the potential role of the immune marker in IVDD through enrichment analysis, protein-to-protein network analysis, and molecular prediction. By analysising of the training set, we revealed significant differences in gene expression of five methylation regulators including RBM15, YTHDC1, YTHDF3, HNRNPA2B1 and ALKBH5, while finding characteristic immune infiltration of differentially expressed genes, the result was validated by PCR. We then screen the differential m6A regulators in the training set and identified RBM15 and YTHDC1 as key m6A regulators. We then used RBM15 and YTHDC1 to construct a predictive model for IVDD and successfully validated it in the training set. Next, we clustered IVDD patients based on the expression of RBM15 and YTHDC1 and explored the immune infiltration characteristics between clusters as well as the expression of RBM15 and YTHDC1 in the clusters. YTHDC1 was finally identified as an immune biomarker for IVDD. We finally found that YTHDC1 may influence the immune microenvironment of IVDD through ABL1 and TXK. In summary, our results suggest that YTHDC1 is a potential biomarker for the development of IVDD and may provide new insights for the precise prevention and treatment of IVDD.

Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide.

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.

Effects of medicine food homologous materials on food allergy-associated factors: intestinal oxidative stress, intestinal inflammation and Th2 immune response.

BACKGROUND: Food allergies could be regulated via Th1/Th2 balance, intestinal oxidative stress and inflammation, which were considered as food allergy-associated factors. Medicine-food homologous materials (MFHM) were considered as a significant factor with respect to preventing human diseases. To evaluate the associations between MFHM and food allergy-associated factors, two types of MFHM with the remarkable function of anti-oxidation and anti-inflammation, Gardeniae fructus (Gar) and Sophorae glos (Sop), were chosen. RESULTS: By constructing an H2O2-induced oxidative stress model of Caco-2 cells and an intestinal inflammatory cell model of Caco-2 cells with tumor necrosis factor-α and interleukin (IL)-13, the contents of anti-oxidative enzymes (SOD and GSH), inflammatory factor (IL-8) and tight junction proteins (zonula occludens-1, occludin and claudin-1) in Caco-2 cells were determined. Moreover, the anti-allergic effects of digestive Sop and Gar were evaluated by measuring the levels of Th1/Th2/Treg cytokines in the spleen cells of sensitized mice. The results showed that the SOD and GSH were obviously increased and the gene and protein expression of IL-8 and claudin-1 were improved with the incubation of digested Sop. Th2 cytokine was reduced and Th1/Th2 balance was promoted on coincubation with ovalbumin (OVA) and digested Sop in the splenocytes. However, the digested Gar had no effect. CONCLUSION: The digested Sop not only had suppressive effects on intestinal oxidative stress and inflammation, but also had regulative effects on Th1/Th2 balance. This finding demonstrated that not all of the MFHM with anti-oxidant and anti-inflammatory effects have anti-allergic activities. The present study may be contributing toward establishing a screening model to identify the anti-allergic MFHM. © 2024 Society of Chemical Industry.

Transcriptome Analysis Reveals Key Genes Involved in the Response of Pyrus betuleafolia to Drought and High-Temperature Stress.

Drought and high-temperature stress are the main abiotic stresses that alone or simultaneously affect the yield and quality of pears worldwide. However, studies on the mechanisms of drought or high-temperature resistance in pears remain elusive. Therefore, the molecular responses of Pyrus betuleafolia, the widely used rootstock in pear production, to drought and high temperatures require further study. Here, drought- or high-temperature-resistant seedlings were selected from many Pyrus betuleafolia seedlings. The leaf samples collected before and after drought or high-temperature treatment were used to perform RNA sequencing analysis. For drought treatment, a total of 11,731 differentially expressed genes (DEGs) were identified, including 4444 drought-induced genes and 7287 drought-inhibited genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these DEGs were more significantly enriched in plant hormone signal transduction, flavonoid biosynthesis, and glutathione metabolism. For high-temperature treatment, 9639 DEGs were identified, including 5493 significantly upregulated genes and 4146 significantly downregulated genes due to high-temperature stress. KEGG analysis showed that brassinosteroid biosynthesis, arginine metabolism, and proline metabolism were the most enriched pathways for high-temperature response. Meanwhile, the common genes that respond to both drought and high-temperature stress were subsequently identified, with a focus on responsive transcription factors, such as MYB, HSF, bZIP, and WRKY. These results reveal potential genes that function in drought or high-temperature resistance. This study provides a theoretical basis and gene resources for the genetic improvement and molecular breeding of pears.

Enhancing Structure Stability by Mg/Cr Co-Doped for High-Voltage Sodium-Ion Batteries.

P2-Na2/3Ni1/3Mn2/3O2 cathode materials have garnered significant attention due to their high cationic and anionic redox capacity under high voltage. However, the challenge of structural instability caused by lattice oxygen evolution and P2-O2 phase transition during deep charging persists. A breakthrough is achieved through a simple one-step synthesis of Cr, Mg co-doped P2-NaNMCM, resulting in a bi-functional improvement effect. P2-NaNMCM-0.01 exhibits an impressive capacity retention rate of 82% after 100 cycles at 1 C. In situ X-ray diffraction analysis shows that the "pillar effect" of Mg mitigates the weakening of the electrostatic shielding and effectively suppresses the phase transition of P2-O2 during the charging and discharging process. This successfully averts serious volume expansion linked to the phase transition, as well as enhances the Na+ migration. Simultaneously, in situ Raman spectroscopy and ex situ X-ray photoelectron spectroscopy tests demonstrate that the strong oxygen affinity of Cr forms a robust TM─O bond, effectively restraining lattice oxygen evolution during deep charging. This study pioneers a novel approach to designing and optimizing layered oxide cathode materials for sodium-ion batteries, promising high operating voltage and energy density.

Shedding light on the interaction of ovalbumin and resveratrol: structure, digestibility, transport, and allergenicity assessment of OVA-RES complexes.

BACKGROUND: The interaction between food allergens and plant polyphenols has become a safe and effective management strategy to prevent food allergies. Ovalbumin (OVA) is the most abundant allergen in egg whites. Resveratrol (RES) is a plant polyphenol that is abundant in red grapes, berries, and peanuts, and has an anti-allergic effect on allergy-related immune cells. However, there is little information about the effect of RES on the allergenicity of OVA. In this study, the effect of RES on the allergenicity of OVA was investigated. RESULTS: Molecular docking and spectroscopic studies indicated that the addition of RES changed the structure of OVA. The digestion and transfer rate of OVA-RES were effectively improved with an in vitro gastrointestinal digestion model and Caco-2 cell model, especially when the molar ratio of OVA-RES was 1:20. Meanwhile, the KU812 cell degranulation assay proved that the potential allergenicity was remarkably decreased while the molar ratios of OVA-RES were increased to 1:20. Furthermore, hydrogen bonds and van der Waals forces were the dominating forces to stabilize the OVA-RES complexes. CONCLUSION: All the findings demonstrated that the potential allergenicity of OVA was reduced when interacting with RES, and RES can be a potential food material for preparing a hypoallergenic protein, especially for egg allergy. © 2023 Society of Chemical Industry.

Effect of Air Pollutants and Meteorological Factors on Daily Outpatient Visits of Allergic Rhinitis in Hohhot, China.

Objective: There is limited evidence that atmospheric pollutants are associated with the number of allergic rhinitis (AR) visits. This study aimed to investigate the relationship between atmospheric pollutants and meteorological factors and the number of daily visits for AR in Hohhot City, providing a theoretical basis for further research on the effects of atmospheric pollutants on AR. Methods: Microsoft Excel 2016 was used to collect and organize the AR outpatient consultation data, air pollution and meteorological data in Hohhot City during 2018-2020, and the data were descriptively analyzed and Spearman correlation test was performed using SPSS22.0; A generalized additive model was built in R4.2.3 to analyze the effect of air pollution on the number of AR visits and its lagged and cumulative effects, while the robustness of the model was tested using a two-pollutant analysis. Finally, we analyzed the effects of the interaction of temperature, relative humidity and pollutants on the number of AR visits. Results: The daily average concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 in Hohhot during 2018-2020 were 38.1 µg/m3, 83.3 µg/m3, 36.1 µg/m3, 15.1 µg/m3, 14.2 mg/m3, and 99.95 µg/m3, respectively, with the concentrations of PM2.5 and PM10 exceeding the secondary limit of the national standard. The results of the generalized additive model analysis showed that the RR and 95% CI of the effect of each 10 µg/m3 increase in pollutant concentration (1 mg/m3 increase in CO) on the number of AR outpatient clinics were 1.008 (1.001-1.016), 1.002 (1-1.005), 1.072 (1.033-1.113), 1.020 (1007-1.034), 1.033 (1.014-1.052), 0.987 (0.9804-0.9936). Conclusion: Short-term exposure to PM2.5, PM10, SO2, NO2, and CO was significantly associated with an increase in AR clinic visits, and short-term exposure to O3 was significantly associated with a decrease in allergic rhinitis clinic visits.

Pregabalin inhibits purinergic P2Y2 receptor and TRPV4 to suppress astrocyte activation and to relieve neuropathic pain.

BACKGROUNDS: Transient receptor potential vanilloid 4 (TRPV4)-mediated astrocyte activation is critical to neuropathic pain. Pregabalin, a widely used drug to treat chronic pain, is reported to lower the intracellular calcium level. However, the molecular mechanism by which pregabalin decreases the intracellular calcium level remains unknown. Purinergic P2Y2 receptor-a member of the G protein-coupled receptor (GPCR) family-regulates calcium-related signal transduction in astrocyte activation. We investigated whether P2Y2 receptor is involved in the pharmacological effects of pregabalin on neuropathic pain. METHODS: Neuropathic pain was induced by chronic compression of the dorsal root ganglion (CCD) in rats. Paw withdrawal mechanical threshold (PWMT) was used for behavioral testing. Intracellular calcium concentration was measured using a fluorescent calcium indicator (Fluo-4 AM). RESULTS: We found that P2Y2 receptor protein was upregulated and astrocytes were activated in the experimental rats after CCD surgery. Lipopolysaccharide (LPS) increased the intracellular calcium concentration and induced astrocyte activation in cultured astrocytes but was prevented via P2Y2 receptor inhibitor AR-C118925 or pregabalin. Furthermore, plasmid-mediated P2Y2 receptor overexpression induced an elevation of the intracellular calcium levels and inflammation in astrocytes, which was abolished by the TRPV4 inhibitor HC-067047. AR-C118925, HC-067047, and pregabalin relieved neuropathic pain and inflammation in rats after CCD surgery. Finally, plasmid-mediated P2Y2 receptor overexpression induced neuropathic pain in rats, which was abolished by pregabalin administration. CONCLUSIONS: Pathophysiological variables that upregulated the P2Y2 receptor/TRPV4/calcium axis contribute to astrocyte activation in neuropathic pain. Pregabalin exerts an analgesic effect by inhibiting this pathway.

Association of the rs3917647 polymorphism of the SELP gene with malnutrition in gastric cancer.

BACKGROUND: Malnutrition and cachexia are common syndromes in patients with gastric cancer (GC) and are associated with poor quality of life and poor disease prognosis. However, there is still a lack of molecular factors that can predict malnutrition or cachexia in cancer. Studies have shown that among the potential contributors to the development of cancer cachexia, the level of the inflammatory response to P-selectin is regulated by single nucleotide polymorphisms (SNPs) located in the promoter region of the SELP gene. The aim of this study was to evaluate the association between the single nucleotide polymorphism (SNP)-2028 A/G of the SELP gene and malnutrition in patients receiving chemotherapy for gastric cancer (GC). METHODS: The study group consisted of 220 GC patients treated with chemotherapy at Jinhua Municipal Central Hospital. DNA was extracted from peripheral leukocytes of whole blood samples using an animal DNA extraction kit. DNA was amplified using a 1.1 × T3 Super PCR mix, and loci corresponding to the peaks were genotyped using SNP1 software. RESULTS: Patients carrying the A allele had a reduced risk of developing malnutrition compared to patients with the GG genotype (P < 0.001; OR = 3.411; 95% CI = 1.785-6.516). In addition, multivariate analysis indicated that the AA genotype significantly (more than 16-fold) reduced the risk of developing malnutrition (P < 0.001; OR = 0.062; 95% CI = 0.015-0.255). CONCLUSION: SELP -2028A/G SNP may be a useful marker for assessing the risk of malnutrition in GC patients.

Relationship Between Outdoor Air Pollutant Exposure and Premature Delivery in China- Systematic Review and Meta-Analysis.

Objective: Preterm birth (PTB) is considered as a public health problem and one of the main risk factors related to the global disease burden. The purpose of this study aims to explore the influence of exposure to major air pollutants at different pregnancies on PTB. Methods: The relationship between air pollutants and PTB in China was collected from cohort studies and case-control studies published before 30 April 2022. Meta-analysis was carried out with STATA 15.0 software. Results: A total of 2,115 papers were retrieved, of which 18 papers met the inclusion criteria. The comprehensive effect of pollutant exposure and PTB were calculated. PM2.5 during entire pregnancy and O3 exposure during third trimester were positively associated with preterm birth. Every 10 µg/m3 increase in the average concentration of PM2.5 during the whole pregnancy will increase the risk of premature delivery by 4%, and every 10 µg/m3 increase in the average concentration of O3 in the third trimester will increase the risk of premature delivery by 1%. Conclusion: Exposure to PM2.5 entire prenatal pregnancy and O3 in third trimester is associated with an increased risk of preterm birth occurrence.