GZMA suppressed GPX4-mediated ferroptosis to improve intestinal mucosal barrier function in inflammatory bowel disease.

BACKGROUND: Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. METHODS: Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. RESULTS: Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. CONCLUSION: These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.

The evolutionary advantage of artemisinin production by Artemisia annua.

Artemisinin, a potent antimalarial compound, is predominantly derived from Artemisia annua. The uniqueness of artemisinin production in A. annua lies in its complex biochemical pathways and genetic composition, distinguishing it from other plant species, even within the Asteraceae family. In this review, we investigate the potential of A. annua for artemisinin production, drawing evidence from natural populations and mutants. Leveraging high-quality whole-genome sequence analyses, we offer insights into the evolution of artemisinin biosynthesis. We also highlight current understanding of the protective functions of artemisinin in A. annua in response to both biotic and abiotic stresses. In addition, we explore the mechanisms used by A. annua to mitigate the phytotoxicity generated by artemisinin catabolism.

RfaH contributes to maximal colonization and full virulence of hypervirulent Klebsiella pneumoniae.

Hypervirulent K. pneumoniae (hvKp) have emerged as clinically important pathogens, posing a serious threat to human health. RfaH, a transcriptional elongation factor, has been regarded as implicated in facilitating the transcription of long virulence operons in certain bacterial species. In K. pneumoniae, RfaH plays a vital role in promoting CPS synthesis and hypermucoviscosity, as well as mediating bacterial fitness during lung infection. In this study, we aim to conduct a systematic investigation of the roles of rfaH in the survival, dissemination, and colonization of hvKp through in vitro and in vivo assays. We found that bacterial cells and colonies displayed capsule -deficient phenotypes subsequent to the deletion of rfaH in K. pneumoniae NTUH-K2044. We confirmed that rfaH is required for the synthesis of capsule and lipopolysaccharide (LPS) by positively regulating the expression of CPS and LPS gene clusters. We found that the ΔrfaH mutant led to a significantly decreased mortality of K. pneumoniae in a mouse intraperitoneal infection model. We further demonstrated that the absence of rfaH was associated with slower bacterial growth under conditions of low nutrition or iron limitation. ΔrfaH displayed reduced survival rates in the presence of human serum. Besides, the engulfment of the ΔrfaH mutant was significantly higher than that of NTUH-K2044 by macrophages in vivo, indicating an indispensable role of RfaH in the phagocytosis resistance of hvKp in mice. Both mouse intranasal and intraperitoneal infection models revealed a higher bacterial clearance rate of ΔrfaH in lungs, livers, and spleens of mice compared to its wild type, suggesting an important role of RfaH in the bacterial survival, dissemination, and colonization of hvKp in vivo. Histopathological results supported that RfaH contributes to the pathogenicity of hvKp in mice. In conclusion, our study demonstrates crucial roles of RfaH in the survival, colonization and full virulence of hvKp, which provides several implications for the development of RfaH as an antibacterial target.

The management of exercise-induced anaphylaxis in a Chinese child with biologics: a case report.

Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder. In difficult to control and refractory cases of EIA, biologics such as omalizumab and dupilumab have shown promise, with documented successful outcomes. Here, we present a case of EIA with lipid transfer protein (LTP) sensitization successfully treated with omalizumab with long-term follow-up. A 12-year-old girl presented to our allergy department because of recurrent episodes of EIA, with no specific food ingestion before exercise. Allergen testing revealed sensitization to weed pollens, particularly mugwort (76.1 kUA/L) and Alternaria alternata (10.8 kUA/L). Allergen component testing indicated sensitization to LTP components from mugwort Art v 3 (49.9 kUA/L), wheat Tri a 14 (2.03 kUA/L), and peach Pru p 3 (11.5 kUA/L), with a negative result for omega-5 gliadin. Despite initial prophylactic treatment with budesonide-formoterol (80/4.5 µg) and cetirizine (10 mg) before exercise, the patient still experienced EIA; she was then recommended for dupilumab therapy (an initial dose of 600 mg, followed by 300 mg every 2 weeks for six doses). However, even while undergoing dupilumab therapy, she suffered two anaphylactic episodes after running 800-1,000 m. With the patient's consent, a trial of omalizumab was initiated (injections of 300 mg every 4 weeks). After 2 months of omalizumab therapy, the patient showed significant improvement. She had been engaging in physical exercise three times a week and experienced a mild episode of urticaria. There were no further episodes of anaphylaxis or emergency room visits. By the fourth month of omalizumab treatment, she was able to consume food normally even just before exercising and had returned to her full activity level without any restrictions. This case presents the first successful off-label use of omalizumab in the prevention of EIA in the Chinese population. It is concluded that omalizumab may be helpful in resolving EIA symptoms, as evidenced by this case of successful long-term use.

Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, Jilin Province, China, 2010-March 2024.

Varicella is endemic worldwide. In China, varicella has not yet been included in the list of legal infectious diseases, nor has a unified national surveillance program been established. And the live attenuated varicella vaccine has not been included in routine immunization. In this study, we analyzed for the first time the varicella epidemiology in Jilin Province in the past 20 years, and the nucleotide site, amino acid site and N-glycosylation site variation of glycoprotein in varicella-zoster virus (VZV) surface 9 in the past 15 years. The results showed that the reported incidence of varicella in Jilin Province in the last 20 years was fluctuating above and below 20/100,000, especially after the epidemic of the COVID-19, and fatal cases appeared in individual years. The genotypic branching of VZV was monitored as Clade 2 in the last 15 years. 9 glycogen nucleotide sites of VZV had different degrees of variability, and the variability had specificity. Therefore, it gives us the idea that in order to reduce the incidence of varicella and herpes zoster, a provincial or even national surveillance program should be introduced as early as possible, and the dynamic monitoring of the variability of the nucleotide sites of VZV should be strengthened at the same time as the vaccine immunization strategy is introduced.

Solitary Myofibroma of the oral and maxillofacial regions in pediatric patients: A clinicopathological analysis of ten patients and review of 75 cases.

BACKGROUND: The imaging manifestations of oral and maxillofacial myofibroma/myofibromatosis can vary among patients. Although many clinical cases have been reported, a consensus on the clinicopathological features of and treatment principles for this disease is lacking. PURPOSE: This study aimed to summarize the clinicopathological features of solitary myofibroma of the oral and maxillofacial regions in pediatric patients. METHODS: The clinical data, histological features, and immunohistochemical characteristics of ten pediatric patients who underwent surgical removal and subsequent pathological diagnosis of myofibroma were collected and retrospectively and cross-sectionally analyzed. RESULTS: Seven patients were male, and 3 were female, with ages ranging from 3 months to 6 years (mean: 2.6 years). The patients presented with solitary lesions involving the mandibular gingiva and adjacent mandible (4 patients), mandible (2 patients), oral floor and submandibular area and adjacent mandible (1 patient), gingiva (1 patient), maxilla (1 patient), and oropharynx (1 patient). Light microscopy revealed spindle-shaped tumor cells organized in bundles or vortex patterns, forming a hemangiopericytoma-like perivascular pattern, whereas immunohistochemical staining revealed diffuse smooth muscle actin (SMA) positivity. All patients underwent surgical resection, and none experienced recurrence over the 12- to 82-month follow-up. CONCLUSIONS: Solitary myofibroma in the oral and maxillofacial regions is predominantly observed in infants and young children, with a higher incidence among males. The prognosis is favorable following localized lesion resection or curettage of jawbone lesions. Accurate recognition of the clinical, radiological, and pathological features of the disease will reduce the misdiagnosis rate.

Sub-180-nanometer-thick ultraconformable high-performance carbon nanotube-based dual-gate transistors and differential amplifiers.

There is increased interest in ultrathin flexible devices with thicknesses of <1 micrometers due to excellent conformability toward advanced laminated bioelectronics. However, because of limitations in materials, device structure, and fabrication methodology, the performance of these ultrathin devices and circuits is insufficient to support higher-level applications. Here, we report high-performance carbon nanotube-based thin-film transistors (TFTs) and differential amplifiers on ultrathin polyimide films with a total thickness of <180 nanometers. A dual-gate structure is introduced to guarantee excellent gate control efficiency and mechanical stability of the ultrathin TFTs, which exhibit high transconductance (8.96 microsiemens per micrometer), high mobility (127 square centimeters per volt per second), and steep subthreshold swing (84 millivolts per decade), and can sustain a bending radius of curvature of <10 micrometers. The differential amplifier achieves the highest gain-bandwidth product (1.83 megahertz) among flexible differential amplifiers, enabling higher-gain amplification of weak signals over an extended frequency spectrum that is demonstrated by amplification of electromyography signals in situ.

Impact of human papillomavirus and coinfection with other sexually transmitted pathogens on male infertility.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Staphylococcus aureus. A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.

Evaluation of barley genotypes for drought adaptability: based on stress indices and comprehensive evaluation as criteria.

The prevalence of drought events worldwide emphasizes the importance of screening and cultivating drought-adapted crops. In this study, 206 germplasm resources were used as materials, dry weight as target trait, and two genotyping methods as criteria to evaluate drought adaptability at the seedling establishment stage. The results showed a significant decrease in average dry weight of the tested germplasm resources (from 746.90 mg to 285.40 mg) and rich variation in the responses of dry weight among each genotype to drought (CV=61.14%). In traditional evaluation method, drought resistance coefficient (DC), geometric mean productivity index (GMP), mean productivity index (MP), stress susceptibility index (SSI), stress tolerance index (STI), and tolerance index (TOL) also exhibited diversity in tested genotypes (CV>30%). However, these indices showed varying degrees of explanation for dry weight under stress and non-stress environments and failed to differentiate drought adaptability among genotypes clearly. In new evaluation method, four stress indices were developed to quantify barley seedling production and stability capacities. Compared to traditional stress indices, the stress production index (SI) explained dry weight more comprehensively under stress conditions (R2 = 0.98), while the ideal production index (II) explained dry weight better under non-stress conditions (R2 = 0.89). Furthermore, the potential index (PI) and elasticity index (EI) eliminated disparities in traditional stress indices and comprehensively clarified the contribution of elasticity and potential to production capacity under drought stress. Ultimately, through grading evaluation and cluster analysis, the tested germplasm resources were effectively categorized, and 11 genotypes were identified as suitable for cultivation in arid areas. Overall, the comprehensive evaluation method based on the newly developed stress indices surpasses the traditional method in screening drought adaptability of crops and serves as a vital tool for identifying high-stability and high-production capacities genotypes in various environments, which is expected to provide practical guidance for barley planting and breeding in arid areas.

Copper tannate nanosheets-embedded multifunctional coating for antifouling and photothermal bactericidal applications.

Implant-associated infections (IAIs), triggered by pathogenic bacteria, are a leading cause of implant failure. The design of functionalized coatings on biomedical materials is crucial to address IAIs. Herein, a multifunctional coating with good antifouling effect and antibacterial photothermal therapy (aPTT) performance was developed. The copper tannate nanosheets (CuTA NSs) were formed via coordination bonding of Cu2+ ions and tannic acid (TA). The CuTA NSs were then integrated into the TA and poly(ethylene glycol) (PEG) network to form the TCP coating for deposition on the titanium (Ti) substrates via surface adhesion of TA and gravitational effect. The resulting Ti-TCP substrate exhibited good antifouling property, reactive oxygen species (ROS) scavenging capability and cytocompatibility. The TCP coating exhibited antifouling efficacy in conjunction with aPTT, curtailing the surface adhesion and biofilm formation of pathogens, such as Staphylococcus aureus and Escherichia coli. Notably, the Ti-TCP substrate also exhibited the ability to prevent bacterial infection in vivo in a subcutaneous implantation model. The present work demonstrated a promising approach in designing high-performance antifouling and photothermal bactericidal coatings to combat IAIs.

The association between mode of childbirth delivery and early childhood caries: A comprehensive systematic review and meta-analysis.

BACKGROUND: Early childhood caries (ECC), also known as dental caries, poses a significant challenge to the oral health and overall well-being of young children. This study aims to investigate the potential relationship between the mode of delivery and the odds of ECC. METHODS: We conducted a meticulous systematic review and meta-analysis, gathering studies from reputable databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The selected studies underwent rigorous evaluation for heterogeneity, utilizing statistical tests such as the Chi-square test, I2, meta-regression analysis, sensitivity analysis, and subgroup analysis. We assessed the presence of publication bias using Begg's and Egger's tests, while the quality of the articles was evaluated using the Newcastle-Ottawa Scale checklist. RESULTS: Our analysis included a robust dataset of 24 studies conducted between 1997 and 2024, involving a total of 71,732 participants. The meta-analysis revealed an odds ratio of 1.05 (95% CI: 0.86-1.30; P-value = 0.610) for dental caries in children born via cesarean section. Importantly, we found no evidence of publication bias, as indicated by non-significant results from Begg's test (P-value = 0.568) and Egger's test (P-value = 0.807). Meta-regression analysis did not identify any significant associations between the study variables and the observed heterogeneity (P > 0.10). Sensitivity analysis further confirmed the stability of the study results, with no significant changes detected. CONCLUSION: In conclusion, our comprehensive meta-analysis provides compelling evidence that there is no significant association between the mode of delivery and the odds of ECC. These findings enhance our understanding of this important topic and have implications for clinical practice and public health interventions.

In vitro digestion and antioxidant activity of Xuan-Mugua (Chaenomeles fruit) peel and pulp phenolics.

Since time immortal, people have used the well-known Chinese Chaenomeles fruit Xuan-Mugua for both traditional medicine and nourishment. With an aim to explore the digestive and antioxidant properties of the phenolics, Xuan-Mugua peel and pulp were extracted, digested and analyzed in vitro. Our results indicated that the total phenolics content (TPC), total flavonoids content (TFC) and the antioxidant activity of the peel were 3.24-8.89 times higher than that of pulp. The contents and activity of the peel and pulp consistently dropped in the sequence of oral, gastric, and small intestine digestions, from 22.78 % to 52.16 %. With a level of 1.590 ± 0.060 and 0.395 ± 0.015 mg g-1 dried weight in the peel and pulp, respectively, chlorogenic acid was the primary phenolic ingredient in Xuan-Mugua, with a promising recovery (81.39-82.23 %) during the digestion. According to these results, Xuan-Mugua exhibited an appreciable level of phenolic content and antioxidant activity during digestion, making it a suitable ingredient for use in functional foods.

Food-dependent exercise-induced anaphylaxis (FDEIA) suspected triggered by lipid transfer protein in a Chinese child: A case report.

Lipid transfer protein (LTP) has been documented as the dominant protein involved in food-induced anaphylaxis and food-dependent exercise-induced anaphylaxis (FDEIA) patients from Mediterranean European countries. To date, there is no report of FDEIA triggering by LTP in China. A 12-year-old Chinese boy experienced recurrent anaphylaxis during intense exercise for 3 months. Specific immunoglobulin E was performed using ImmunoCAP (Thermo Fisher Scientific, Sweden) and Euroline (EUROIMMUN, Germany). He was sensitized to several pollens, mainly mugwort (62 KUA/L), and was found to have detectable immunoglobulin E in multiple foods: cereal (wheat, barley, oat maize, rice, buckwheat, and common millet), fruits (peach, apple, grape, cherry, and orange), vegetables (lettuce, cabbage, broccoli, cauliflower, tomato, and celery), and legumes and nuts (soybean, peanut, and walnut). He also showed sensitization to LTP components from mugwort Art v3 (79.7 KUA/L) and wheat Tri a14 (12.4 KUA/L), but negative to gluten, gliadin, and omega-5 gliadin. We advised our patient to carry an epinephrine auto-injector, not to exercise alone, and to avoid wheat and fruit/vegetable ingestion for at least 4 hours before exercise or when taking non-steroidal anti-inflammatory drugs. After a 6-month follow-up, the patient has experienced no episode of anaphylaxis. We reported the first documented FDEIA case suspected triggered by LTP in a Chinese child. Clinicians should be aware of LTP sensitization when anaphylaxis occurs during exercise in individuals with multiple pollen and food sensitization.

The Effects of the Multi-Hospital Global Budget Payment on Medical Expenditure and Service Volume: The Evidence from Dangyang County, China.

Background: Global budget payment is currently the prevailing payment strategy internationally. In China, the concept of multi-hospital global budget payment has been proposed with the aims of achieving cost control effects while also encouraging hospital collaboration and optimising allocation of healthcare resources. This study seeks to analyse the impact of multi-hospital global budget payment in China on healthcare expenditure and service volume. Materials and Methods: A retrospective comparative study was carried out in Dangyang County, China. The exposure cases were migrants who were not locally registered in the residence registration system. The study period encompassed January 1, 2017, to December 31, 2019. Including 3,246,164 outpatient medical records and 242,685 inpatient medical records. The key variables are medical expenditure and service volume indicators. Continuous variables were reported as mean and tested by t-test. We used interrupted time series analysis models to estimate the changes in the level and trend of each outcome measure after the policy. Results: After the outpatient global budget payment reform, the monthly medical expenditure of the hospital alliance has transitioned from a discernible upward trajectory to a deceleration in the rate of growth. The outpatient volume in public and private high-level hospitals decreased at a rate of -419.26 person/month and -137.04 person/month, respectively. In terms of inpatient service volume, only private high-level hospitals reported a decrease, with a reduction rate of -15.38 individuals per month. Conclusion: This study presents new evidence demonstrating that the multi-hospital global budget payment can effectively control costs and promote resource reallocation when implemented jointly with hospital alliance policies. However, overly lenient budget caps risk counterproductive effects.

The effect of an innovative payment method on inpatient volume and bed resources and their regional distribution: the case of a central province in China.

BACKGROUND: Since 2020, China has piloted an innovative payment method known as the Diagnosis-Intervention Packet (DIP). This study aimed to assess the impact of the DIP on inpatient volume and bed allocation and their regional distribution. This study investigated whether the DIP affects the efficiency of regional health resource utilization and contributes to disparities in health equity among regions. METHODS: We collected data from a central province in China from 2019 to 2022. The treatment group included 508 hospitals in the pilot area (Region A, where the DIP was implemented in 2021), whereas the control group consisted of 3,728 hospitals from non-pilot areas within the same province. We employed the difference-in-differences method to analyze inpatient volume and bed resources. Additionally, we conducted a stratified analysis to examine whether the effects of DIP implementation varied across urban and rural areas or hospitals of different levels. RESULTS: Compared with the non-pilot regions, Region A experienced a statistically significant reduction in inpatient volume of 14.3% (95% CI 0.061-0.224) and a notable decrease of 9.1% in actual available bed days (95% CI 0.041-0.141) after DIP implementation. The study revealed no evidence of patient consultations shifting from inpatient to outpatient services due to the reduction in hospital admissions in Region A after DIP implementation. Stratified analysis revealed that inpatient volume decreased by 12.4% (95% CI 0.006-0.243) in the urban areas and 14.7% in the rural areas of Region A (95% CI 0.051-0.243). At the hospital level, primary hospitals experienced the greatest impact, with a 19.0% (95% CI 0.093-0.287) decline in inpatient volume. Furthermore, primary and tertiary hospitals experienced significant reductions of 11.0% (95% CI 0.052-0.169) and 8.2% (95% CI 0.002-0.161), respectively, in actual available bed days. CONCLUSIONS: Despite efforts to curb excessive medical service expansion in the region following DIP implementation, large hospitals continue to attract a large number of patients from primary hospitals. This weakening of primary hospitals and the subsequent influx of patients to urban areas may further limit rural patients' access to medical services. The implementation of the DIP may raise concerns about its impact on health care equality and accessibility, particularly for underserved rural populations.

Comparative analysis of the effects of the computer-based and paper-based trail making tests on oxygenation in the prefrontal cortex.

The trail making test (TMT) is a commonly used tool for evaluating executive functions, and the activation of cerebral oxygenation in the prefrontal cortex (PFC) during the test can reflect the participation of executive function. This study aimed to compare the differences in cerebral oxygenation in the PFC between the computer- and paper-based versions of the TMT and provide a theoretical basis for the optimization and clinical application of the computer-based version. A total of 32 healthy adult participants completed the computer- and paper-based TMT Types A and B. Cerebral oxygenation changes in the PFC were monitored during the experiment using near-infrared spectroscopy. Moreover, average changes in oxyhemoglobin (Δoxy-Hb) levels at the baseline and during activation periods in different types of testing were compared and analyzed. The number of correct connections in the computer-based version Type B was less than that in the paper-based version Type B (p < .001). The task time of the computer-based version was longer than that of the paper-based version (p < .001). The B/A ratio of the number of correct connections in the computer-based version was lower than that in the paper-based version (p < .001). The Δoxy-Hb in the PFC of the paper-based version was higher than that of the computer-based version (p < .001). Significant differences in oxygenation in the PFC were observed between the paper- and computer-based versions of TMT. After further improvement and correction in the subsequent development of the computer-based TMT, and taking into account the psychological feelings and preferences of the participants when performing different versions of the TMTs, the computer-based TMT is expected to play a good auxiliary role in clinical evaluation.

POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo. Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p, and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p, miR-29a-3p, PIK3R1, and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1, PIK3R1, and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS: The POU2F1-miR-29b-3p/miR-29a-3p-PIK3R1/PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.

Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect.

N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver cancer. We found that the level of KIAA1429 was significantly elevated in liver cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver cancer cells in vitro and in vivo. RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver cancer treatment.

Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine (TCM). Qingfei Huatan, a TCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre, randomised, double-blind, controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD (AECOPD). OBJECTIVE: This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical evidence. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 months. MAIN OUTCOME MEASURES: The primary outcome was time taken to symptom stabilisation. The secondary outcomes included duration of antibiotic use, clinical symptom and sign score, TCM syndrome score, dyspnoea score, and quality of life (QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the trial. RESULTS: The time taken for effective stabilisation (P < 0.05) and obvious stabilisation (P < 0.01), and the duration of antibiotic use (P < 0.05) were significantly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups, particularly in the treatment group (P < 0.01). On days 9, 12 and 14 of treatment, the TCM syndrome scores of both groups were reduced (P < 0.01), with more significant reductions in the treatment group. At 3 months after the end of treatment, the treatment group continued to have lower clinical symptom and sign score and TCM syndrome score than the control group (P < 0.01). On days 6, 9, 12 and 14 of treatment, dyspnoea and QOL scores were markedly reduced in the two groups (P < 0.05 and P < 0.01, respectively), especially in the treatment group. At 3 months after the end of treatment, dyspnoea and QOL scores were lower in the treatment group than those in the control group (P < 0.01). No serious adverse events were observed in either group. CONCLUSION: The Qingfei Huatan formula can effectively shorten the duration of AECOPD and antibiotic use, significantly relieve clinical symptoms, and increase QOL for AECOPD patients, with a favourable safety profile. These results suggest that this formula can be used as a complementary treatment for AECOPD patients. TRIAL REGISTRATION: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1900026576). Please cite this article as: Zhu HZ, Li CY, Liu LJ, Tong JB, Lan ZH, Tian SG, Li Q, Tong XL, Wu JF, Zhu ZG, Li SY, Li JS. Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial. J Integr Med. 2024; 22(5): 561-569.

Chemical detection and analysis of Astragalus-Cassia twig drug pair using UHPLC-Q-TOF-MS and HPLC-UV methods.

The classic Astragalus-Cassia twig drug pair has a long history of proven efficacy. However, a fewer studies on material basis of the Astragalus and Cassia twig decoction (ACD) was researched at present. The method of UPLC-Q-TOF-MS for classifying and identifying the main chemical components of ACD was established and the differences in composition between single decoction and co-decoction were compared by using HPLC-UV. The therapeutic role of ACD on type 2 diabetes (T2D) rats was investigated. Thirty-five compounds were resolved from the ACD. Fifteen compounds were deduced from the decoction of Astragalus, whereas nine compounds were identified from Cassia twig. Pairing of herbs make a significant effect on the chemical composition of herbal decoction. ACD can play a more obvious role in alleviating the symptoms of T2D rats, compared to the application of single herb.