Water, starch, and nuclear behavior in ray parenchyma during heartwood formation of Catalpa bungei 'Jinsi'.

Catalpa bungei 'Jinsi', a cultivar of C. bungei C. A. Mey., is valued for its heartwood with good overall mechanical properties, naturally durable and golden-yellow color. Little is known about heartwood formation in C. bungei 'Jinsi' trees. The behavior of starch, water, and nuclei was studied in the xylem tissue of C. bungei 'Jinsi' concerning aging in ray parenchyma cells. Blocks containing heartwood, golden zone, transition zone, and sapwood were collected from the stems of six C. bungei 'Jinsi' trees. The moisture content of the blocks was measured by oven drying. Changes in starch and nuclei in ray parenchyma were investigated in radial profiles from sapwood to heartwood blocks using microscopy and various staining techniques. The nuclear size and starch content gradually decreased to heartwood. While the horizontal distribution of moisture content of C. bungei 'Jinsi' was very varied, with the heartwood and golden zone being lower than sapwood but slightly higher than the transition zone. Starch grains were rare, but nuclei were still present in some ray parenchyma cells in the heartwood and golden zone. The nuclei showed irregular shape and elongation before disintegration. These results suggest that the most apparent change occurs in the transition zone, the critical location involved in forming C. bungei 'Jinsi' heartwood. Water and starch appear to be actively engaged in heartwood formation. The loss of function of ray parenchyma cells results from heartwood formation.

Comparison of the Profile and Management of Chronic Pancreatitis between China and Western Countries: A Single-Center Experience and Literature Review.

OBJECTIVE: The etiology, clinical presentation, diagnosis, and treatment strategies of chronic pancreatitis (CP) vary significantly between countries. Specifically, the etiology and surgical approaches to treating CP differ between China and Western countries. Therefore, this study aims to compare the disparities in CP profiles and management based on our single-center experience and recent data from the West. METHODS: From January 2007 to December 2017, a total of 130 consecutive patients with histologically confirmed chronic pancreatitis (CP) underwent surgical treatment at the First Affiliated Hospital of Nanjing Medical University. The clinical features, etiology, risk factors, and operative procedures of these CP patients were analyzed and compared with recent data from Western countries. RESULTS: Our patient cohort was predominantly male (3.19:1), with a median age of 50.2 ± 9.8 years. Upper abdominal pain was the most common symptom, present in 102 patients (78.5%). The most common etiology was obstructive factors (47.7%), followed by alcohol (34.6%). The incidence of genic mutation was 2%, significantly lower than rates reported in Western research. Steatorrhea, weight loss, and jaundice were present in 6.9%, 18.5%, and 17.7% of patients, respectively. Pancreatic cysts or pseudocysts were diagnosed in 7 patients (5.4%). The following procedures were performed: Partington procedure in 33 patients (25.4%), Frey procedure in 17 patients (13.2%), Berne procedure in 5 patients (3.9%), Beger procedure in 1 patient (0.8%), pancreaticoduodenectomy in 17 patients (13.1%), pylorus-preserving pancreaticoduodenectomy in 18 patients (13.9%), middle pancreatectomy in 1 patient (0.8%), and distal pancreatectomy in 9 patients (6.9%). Choledochojejunostomy was performed in 14 patients (10.8%), gastroenterostomy in 2 (1.5%), and 15 patients (11.5%) underwent aspiration biopsy. CONCLUSION: Our study confirms that, etiologically, obstructive chronic pancreatitis (CP) is more frequent in the Chinese population than in Western populations. Although diagnostic instruments and operative procedures in China and Western countries are roughly comparable, slight differences exist in relation to diagnostic flowcharts/criteria and the indications and optimal timing of surgery.

N-glycolylneuraminic acid in red meat and processed meat is a health concern: A review on the formation, health risk, and reduction.

One of the most consistent epidemiological associations between diet and human disease risk is the impact of consuming red meat and processed meat products. In recent years, the health concerns surrounding red meat and processed meat have gained worldwide attention. The fact that humans have lost the ability to synthesize N-glycolylneuraminic acid (Neu5Gc) makes red meat and processed meat products the most important source of exogenous Neu5Gc for humans. As our research of Neu5Gc has increased, it has been discovered that Neu5Gc in red meat and processed meat is a key factor in many major diseases. Given the objective evidence of the harmful risk caused by Neu5Gc in red meat and processed meat to human health, there is a need for heightened attention in the field of food. This updated review has several Neu5Gc aspects given including biosynthetic pathway of Neu5Gc and its accumulation in the human body, the distribution of Neu5Gc in food, the methods for detecting Neu5Gc, and most importantly, a systematic review of the existing methods for reducing the content of Neu5Gc in red meat and processed meat. It also provides some insights into the current status and future directions in this area.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Segmenting tourists' motivations via online reviews: An exploration of the service strategies for enhancing tourist satisfaction.

Tourism motivation and satisfaction are classic themes in tourism research. This study combines latent Dirichlet allocation (LDA) and the Censydiam motivation model to analyze online reviews of tourism in Qinghai, China. The aim of this research is to explore tourist motivation through online reviews and provide innovative service suggestions to improve tourist satisfaction. The LDA model initially extracts six main topics from online comments. Then, using the fuzzy analytic hierarchy process (FAHP), it maps the relationship between topics and tourism motivations to propose strategies for enhancing tourists' enjoyment, conviviality, and other motivating factors. Furthermore, we employ the Kano model to evaluate tourists' satisfaction levels regarding these strategies, demonstrating their positive evaluations. Hence, this study provides tourism industry professionals and service designers with an innovative method for understanding tourists' motivations through online reviews, enabling them to design specific services that enhance tourism experiences.

Mapping and Screening of Candidate Gene Regulating the Biomass Yield of Sorghum (Sorghum bicolor L.).

Biomass yield is one of the important traits of sorghum, which is greatly affected by leaf morphology. In this study, a lobed-leaf mutant (sblob) was screened and identified, and its F2 inbred segregating line was constructed. Subsequently, MutMap and whole-genome sequencing were employed to identify the candidate gene (sblob1), the locus of which is Sobic.003G010300. Pfam and homologous analysis indicated that sblob1 encodes a Cytochrome P450 protein and plays a crucial role in the plant serotonin/melatonin biosynthesis pathway. Structural and functional changes in the sblob1 protein were elucidated. Hormone measurements revealed that sblob1 regulates both leaf morphology and sorghum biomass through regulation of the melatonin metabolic pathway. These findings provide valuable insights for further research and the enhancement of breeding programs, emphasizing the potential to optimize biomass yield in sorghum cultivation.

Bacteroides thetaiotaomicron ameliorates mouse hepatic steatosis through regulating gut microbial composition, gut-liver folate and unsaturated fatty acids metabolism.

Gut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy. Bacteroides genus, the enriched gut symbionts, has shown promise in treating fatty liver. However, further investigation is needed to identify specific beneficial Bacteroides strains for metabolic disorders in NAFLD and elucidate their underlying mechanisms. In this study, we observed a positive correlation between the abundance of Bacteroides thetaiotaomicron (B. theta) and the alleviation of metabolic syndrome in the early and end stages of NAFLD. Administration of B. theta to HFD-fed mice for 12 weeks reduced body weight and fat accumulation, decreased hyperlipidemia and insulin resistance, and prevented hepatic steatohepatitis and liver injury. Notably, B. theta did not affect these indicators in low-fat diet (LFD)-fed mice and exhibited good safety. Mechanistically, B. theta regulated gut microbial composition, characterized by a decreased Firmicutes/Bacteroidetes ratio in HFD-Fed mice. It also increased gut-liver folate levels and hepatic metabolites, alleviating metabolic dysfunction. Additionally, treatment with B. theta increased the proportion of polyunsaturated fatty acid in the mouse liver, offering a widely reported benefit for NAFLD improvement. In conclusion, this study provides evidence that B. theta ameliorates NAFLD by regulating gut microbial composition, enhancing gut-liver folate and unsaturated fatty acid metabolism, highlighting the therapeutic role of B. theta as a potential probiotic for NAFLD.

Burden of osteoarthritis in China, 1990-2019: findings from the Global Burden of Disease Study 2019.

This study aimed to report the most current data on the incidence and disability-adjusted life years (DALY) associated with osteoarthritis in China from 1990 to 2019. Publicly available modelled data from Global Burden of Disease Study (GBD) 2019 were used. The incidence and DALY, due to osteoarthritis in China, stratified by sex, trends of associated risk factors, assess the age, period, and cohort effects on the long-term trends of osteoarthritis incidence and DALY in China from 1990 to 2019. We found that the age-standardized incidence and DALY rates of osteoarthritis in China are higher than the average levels in Asia, Africa, and Oceania. In 2019, the number of cases of osteoarthritis in China was 10,681,311, an increase of 132.66% compared with 1990. the DALY of osteoarthritis in China was 4,724,885 person-years, which was 159.70% higher than that in 1990. In 2019, the incidence and DALY rates of osteoarthritis in China was 750.96/100,000,332.19/100,000. High body-mass as risk factors for osteoarthritis DALY with the population attributable proportion (PAF) increasing steadily from 1990 to 2019. The incidence and DALY rates of three types of osteoarthritis from high to low are osteoarthritis knee, osteoarthritis hand, and osteoarthritis hip. Age-period-cohort model showed that the incidence rate of osteoarthritis in China shows a trend of increasing first and then decreasing with age; concurrently, the DALY rate of osteoarthritis in China increased with age. For the period effect, we found that the period rate ratio (RR) of osteoarthritis incidence and DALY rates kept increasing in the cohort born before 2005-2009, and then, it was gradually reduced by year of birth in the cohort born after 2005-2009. As for cohort effect, the cohort RR of incidence rate of osteoarthritis almost has no change, while the cohort RR of DALY rate of osteoarthritis kept increasing from 1990 to 2019. The burden and impact of osteoarthritis in China are substantial and are increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors is needed to reduce the current and future burden of osteoarthritis in China. Key Points • This paper analyzes the disease burden of osteoarthritis in China for the first time and discusses the influence on the disease burden of osteoarthritis from the perspectives of age, period, and cohort.

Skin-Attachable Ink-Dispenser-Printed Paper Fluidic Sensor Patch for Colorimetric Sweat Analysis.

In situ analysis of sweat biomarkers potentially provides noninvasive lifestyle monitoring and early diagnosis. Quantitative detection of sweat rate is crucial for thermoregulation and preventing heat injuries. Here, a skin-attachable paper fluidic patch is reported for in situ colorimetric sensing of multiple sweat markers (pH, glucose, lactate, and uric acid) with concurrent sweat rate tracking. Two sets of fluidic patterns-multiplexed detection zones and a longitudinal sweat rate channel-are directly printed by an automated ink dispenser from a specially developed ceramic-based ink. The ceramic ink thermal-cures into an impervious barrier, confining sweat within the channels. The ceramic-ink-printed boundary achieves higher pattern resolution, prevents fluid leakage, attains pattern thermal stability, and resistant to organic solvents. The cellulose matrix of the detection zones is modified with nanoparticles to improve the color homogeneity and sweat sensor sensitivity. The sweat rate channel is made moisture sensitive by incorporating a metal-salt-based dye. The change in saturation/color of the detection zones and/or channels upon sweat addition can be visually detected or quantified by a smartphone camera. A cost-effective way is provided to fabricate paper fluidic sensor patches, successfully demonstrating on-body multiplexed evaluation of sweat analytes. Such skin wearables offer on-site analysis, meaningful to an increasingly health-conscious population.

Design, synthesis and biological evaluation of biaryl amide derivatives against SARS-CoV-2 with dual-target mechanism.

The COVID-19 pandemic highlights the urgent need to develop effective small-molecule antivirals. Thirty-three novel biaryl amide derivatives were synthesized and evaluated for anti-coronaviral activity. Some significant SARs were uncovered and the intensive structure modifications led to the most active compounds 8b and 8h. The broad-spectrum anti-coronaviral effects of 8h were validated at RNA and protein levels. 8h inhibits coronavirus replication at multiple stages, from virus entry to virus dsRNA synthesis. The mechanism of action showed that 8h may simultaneously act on 3CLpro and TMPRSS2 to display anti-coronaviral effects. 8h combined with RdRp inhibitor showed synergistic inhibitory activity against coronavirus. This study confirmed that biaryl amide derivatives may be a new class of potential therapeutic agents against coronavirus with multiple target effect, worthy of further investigation.

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database.

BACKGROUND: Bevacizumab is used for the treatment of advanced malignant tumors; it acts by inhibiting angiogenesis. This study aimed to examine adverse events (AEs) of bevacizumab, especially hemorrhage, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to analyze the AEs of bevacizumab using FAERS registration data from January 2004 to September 2022. Clinical information regarding hemorrhagic signals was further analyzed. RESULTS: The number of bevacizumab-associated AE reports was 96,477. Our study found that 892 significant preferred terms (PTs) were spread throughout 25 organ systems. The system organ classes (SOCs) focus on general disorders, administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. A total of 2,847 bevacizumab-related hemorrhage cases were reported, and 37 hemorrhagic signals were identified. Hemorrhagic signals were focused on SOC levels in vascular, gastrointestinal, and nervous system disorders. Colorectal, lung, and breast cancers are the three most common malignancies associated with BV-induced hemorrhage. CONCLUSION: The AE report from the present study confirms the majority of label information for bevacizumab, while also identifying new AEs. In addition, this was a large descriptive study of bevacizumab-induced hemorrhage.

Microstructure Evolution and In Situ Resistivity Response of 2196 Al-Li Alloy during Aging Process.

The microstructure evolution of 2196 Al-Li alloy during aging was investigated by microhardness test, transmission electron microscope (TEM) analysis and in situ resistivity measurement. The results showed that the resistivity of the 2196 Al-Li alloy during aging rapidly decreased during the first few hours, and then gradually increased after reaching the minimum value, which is temperature-dependent. The microstructure of the alloy was dominated by the δ' phase after aging at 160 °C for 2 h while the T1 phase could hardly be seen until it had been aged for 16 h. As the aging time went on, significant ripening appeared for the δ' phase while typical growth could be observed for the T1 phase. The increase in the resistivity of the 2196 Al-Li alloy during aging was attributed to the stronger electron scattering capacity of the T1 precipitation and the coupling effect between the T1 and δ' phases.

Moxibustion influences hippocampal microglia polarization via IL-33/ST2 pathway in Alzheimer's disease mice. / è‰¾ç¸é€šè¿‡ç™½ç»†èƒžä»‹ç´ -33/ç”Ÿé•¿åˆºæ¿€è¡¨è¾¾åŸºå› 2è›‹ç™½é€šè·¯å½±å“é˜¿å°”èŒ¨æµ·é»˜ç— å°é¼ æµ·é©¬å°èƒ¶è´¨ç»†èƒžæžåŒ–.

OBJECTIVES: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway. METHODS: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-ß (Aß), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence. RESULTS: Compared with the control group, the escape latency of the mice in the model group was prolonged (P<0.001, P<0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced (P<0.001), the positive expression of both Aß and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased (P<0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased (P<0.05, P<0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened (P<0.001, P<0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased (P<0.001), the positive expression of Aß and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased (P<0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased (P<0.05, P<0.01, P<0.001). CONCLUSIONS: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aß and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.

Hot Deformation Behavior and Processing Maps of 26CrMo7S Steel Used in Oil Exploration.

The hot deformation behavior and flow stress characteristics of experimental 26CrMo7S steel were analyzed using a thermal simulator under a range of conditions, including a strain rate range of 0.01~10 s-1, a temperature range of 850~1250 °C, and a maximum deformation amount of 70%. The Arrhenius constitutive model was built for the corresponding conditions, and the model's accuracy was verified through error analysis. Additionally, hot processing maps were constructed to analyze the processing zone of the steel under different hot deformation conditions. Finally, the microstructure of the processing zones was observed and verified using the electron backscattered diffraction (EBSD). The results indicate that the interaction of work hardening and dynamic softening influences the hot deformation behavior of 26CrMo7S steel. The Arrhenius constitutive equation with a value of the correlation coefficient (r = 0.99523) accurately predicts the flow behavior of 26CrMo7S steel under different strains. The optimal processing zone obtained with the hot processing maps is within a deformation range of 1010~1190 °C and a strain rate range of 0.01~10-1.5 s-1, and the obtained microstructure is in good agreement with the analysis results.

Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway.

Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.

Screening and Validation of Appropriate Reference Genes for Real-Time Quantitative PCR under PEG, NaCl and ZnSO4 Treatments in Broussonetia papyrifera.

Real-time quantitative PCR (RT-qPCR) has a high sensitivity and strong specificity, and is widely used in the analysis of gene expression. Selecting appropriate internal reference genes is the key to accurately analyzing the expression changes of target genes by RT-qPCR. To find out the most suitable internal reference genes for studying the gene expression in Broussonetia papyrifera under abiotic stresses (including drought, salt, and ZnSO4 treatments), seven different tissues of B. papyrifera, as well as the roots, stems, and leaves of B. papyrifera under the abiotic stresses were used as test materials, and 15 candidate internal reference genes were screened based on the transcriptome data via RT-qPCR. Then, the expression stability of the candidate genes was comprehensively evaluated through the software geNorm (v3.5), NormFinder (v0.953), BestKeeper (v1.0), and RefFinder. The best internal reference genes and their combinations were screened out according to the analysis results. rRNA and Actin were the best reference genes under drought stress. Under salt stress, DOUB, HSP, NADH, and rRNA were the most stable reference genes. Under heavy metal stress, HSP and NADH were the most suitable reference genes. EIF3 and Actin were the most suitable internal reference genes in the different tissues of B. papyrifera. In addition, HSP, rRNA, NADH, and UBC were the most suitable internal reference genes for the abiotic stresses and the different tissues of B. papyrifera. The expression patterns of DREB and POD were analyzed by using the selected stable and unstable reference genes. This further verified the reliability of the screened internal reference genes. This study lays the foundation for the functional analysis and regulatory mechanism research of genes in B. papyrifera.

Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC). Materials and methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results. Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

Clinical analysis of 175 cases of vaginal intraepithelial neoplasia.

OBJECTIVE: To evaluate the risk factors related to vaginal intraepithelial neoplasia (VaIN) severity. STUDY DESIGN: This retrospective study included patients with histologically confirmed VaIN diagnosed at Hubei Provincial Maternal and Child Health Hospital, China, between January 2017 and October 2021. The primary outcomes were persistence, remission, progression, and recurrence. Multiple ordinal logistic regression analysis was used to analyze the risk factors of VaIN severity. RESULTS: A total of 175 patients were included, 135 (77.1%) with VaIN 1, 19 (10.9%) with VaIN 2, and 21 (12%) with VaIN 3. Patients with VaIN 3 were older than those with VaIN1 2 (P < 0.001). The ratio of patients with concomitant cervical lesions increased with VaIN grade (23.7%, 47.4%, and 47.6% for VaIN 1, 2, and 3, respectively). The proportion of patients with intraepithelial neoplasia (CIN) 3 increased with the VaIN grade (3.1%, 44.5%, and 80% for VaIN 1, 2, and 3, respectively, respectively; all P < 0.001). In patients with VaIN 1, 19.4% had regression (spontaneous regression in 90.5%) and 80.6% underwent laser ablation (regression in 93.1%). In patients with VaIN 2 and 3, 3.1% showed no regression, 53.1% underwent laser ablation (regression in 76.4%), and 73.8% underwent excision (regression in 78.7%). Age (OR = 1.05, 95 %CI: 1.01-1.10, P = 0.010) and concomitant cervical lesion (OR = 6.99, 95 %CI: 2.31-21.12, P = 0.001) were independent risk factors for the severity of VaIN. CONCLUSION: Age and cervical lesions might be the risk factors for VaIN severity.

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. OBJECTIVE: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. CONCLUSIONS: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.