With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

Objective: To investigate treatment strategies for chronic periapical periodontitis in prematurely erupted premolars and provide guidance for managing pulp and periapical diseases in young permanent teeth with immature roots. Methods: A regenerative endodontic procedure (REP) was performed on a prematurely erupted maxillary left first premolar (tooth 24) at Nolla stage Ⅶ with chronic apical periodontitis, following standardized protocols including root canal irrigation, disinfection, and coronal sealing. The case was followed up, and a literature review was conducted. Results: Clinical resolution of symptoms was observed on tooth 24, with sustained root development. After a 20-month follow-up, the tooth had restored biological function. Literature synthesis revealed that periapical infections in prematurely erupted permanent teeth predominently arise from pulp exposure and bacterial infection, with retrograde infection being rare. For young permanent teeth with necrotic pulp, regenerative endodontic procedures has been established as the treatment of choice to promote apical closure and root maturation. The critical steps of regenerative endodontic procedures include thorough disinfection, induced bleeding to form a fibrin scaffold, and coronal sealing to facilitate stem cell recruitment and differentiation. Conclusion Regenerative endodontic procedures represents an effective and viable treatment option for prematurely erupted young permanent teeth with chronic periapical periodontitis.

In order to compare the differences in growth and secondary metabolite accumulation of Panax quinquefolius between understory and field planting, growth indexes, photosynthetic characteristics, soil enzyme activities, secondary metabolite contents, and antioxidant activities of P. quinquefolius under different planting modes were examined and compared, and One-way analysis of variance(ANOVA) and correlation analyses were carried out by using the software SPSS 25.0 and GraphPad Prism 9.5. The Origin 2021 software was used for plotting. The results showed that compared with those under field planting, the plant height, leaf length, leaf width, photosynthetic rate, and chlorophyll content of P. quinquefolius under understory planting were significantly reduced, and arbuscular mycorrhizal fungi(AMF) infestation rate and infestation intensity, ginsenoside content, and antioxidant activity were significantly increased. The activities of inter-root soil urease, sucrase, and catalase increased, while the activities of non-inter-root soil urease and alkaline phosphatase increased. Correlation analyses showed that the plant height and leaf length of P. quinquefolius plant were significantly positively correlated with net photosynthetic rate, transpiration rate, chlorophyll content, and electron transfer rate(P<0.05), while ginsenoside content was significantly negatively correlated with net photosynthetic rate, chlorophyll content, and electron transfer rate(P<0.05) and significantly positively correlated with AMF infestation rate and infestation intensity(P<0.05). In addition, ginsenoside content was significantly positively correlated with the activities of inter-root soil sucrase, urease, and catalase(P<0.05). This study provides basic data for revealing the mechanism of secondary metabolite accumulation in P. quinquefolius under understory planting and for exploring and practicing the ecological mode of P. quinquefolius under understory planting.
Panax/microbiology* ; China ; Secondary Metabolism ; Soil/chemistry* ; Photosynthesis ; Plant Leaves/metabolism* ; Chlorophyll/metabolism* ; Mycorrhizae

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

OBJECTIVES: To assess the changes in body composition and nutritional risks faced by children with different stages of acute leukemia (AL). METHODS: Bioelectrical impedance analysis combined with anthropometric measurements was used to detect body composition. This prospective study was conducted from August 2023 to July 2024 at Shandong Provincial Hospital, examining the body composition and physical balance of children with various stages of AL and healthy children. RESULTS: The non-fat components of children with AL and healthy children both showed a linear increase with age. In the younger age group, there were no significant differences in body composition between children with AL and healthy children. However, in the older age group, the body composition of children undergoing chemotherapy for AL was significantly lower than that of healthy children (P<0.05), and muscle mass recovered first after the completion of AL chemotherapy. The proportion of children with increased trunk fat in AL children who completed chemotherapy was significantly lower than that in healthy children (P<0.05), while the incidence rate of severe left-right imbalance in body composition was significantly higher (P<0.05). Muscle distribution in children with AL primarily showed insufficient limb and overall muscle mass, whereas healthy children mainly exhibited insufficient upper limb muscle mass. CONCLUSIONS The body composition of children with AL varies at different treatment stages, indicating that nutritional status is affected by both the disease itself and the treatment. Early screening can provide a basis for reasonable nutritional intervention.
Humans ; Child ; Male ; Female ; Child, Preschool ; Body Composition ; Prospective Studies ; Adolescent ; Leukemia/metabolism* ; Infant ; Nutritional Status ; Acute Disease ; Electric Impedance

OBJECTIVES: To explore the risk factors of feeding intolerance (FI) in critically ill children receiving enteral nutrition (EN) and to construct a prediction nomogram model for FI. METHODS: A retrospective study was conducted to collect data from critically ill children admitted to the Pediatric Intensive Care Unit of Xiangya Hospital, Central South University, between January 2015 and October 2020. The children were randomly divided into a training set (346 cases) and a validation set (147 cases). The training set was further divided into a tolerance group (216 cases) and an intolerance group (130 cases). Multivariate logistic regression analysis was used to screen for risk factors for FI in critically ill children receiving EN. A nomogram was constructed using R language, which was then validated on the validation set. The model's discrimination, calibration, and clinical net benefit were evaluated using receiver operating characteristic curves, calibration curves, and decision curves. RESULTS: Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition were identified as independent risk factors for FI in critically ill children receiving EN (P<0.05). Based on these factors, a nomogram prediction model for FI in critically ill children receiving EN was developed. The area under the receiver operating characteristic curve for the training set and validation set was 0.934 (95%CI: 0.906-0.963) and 0.852 (95%CI: 0.787-0.917), respectively, indicating good discrimination of the model. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good fit (χ 2=12.559, P=0.128). Calibration curve and decision curve analyses suggested that the model has high predictive efficacy and clinical application value. CONCLUSIONS Duration of bed rest, shock, gastrointestinal decompression, use of non-steroidal anti-inflammatory drugs, and combined parenteral nutrition are independent risk factors for FI in critically ill children receiving EN. The nomogram model developed based on these factors exhibits high predictive efficacy and clinical application value.
Humans ; Critical Illness ; Enteral Nutrition/adverse effects* ; Male ; Risk Factors ; Female ; Child, Preschool ; Infant ; Nomograms ; Retrospective Studies ; Child ; Logistic Models

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged