ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules （QDYF） alleviate nasal mucosal remodeling in allergic rhinitis （AR） via the interleukin-33 （IL-33）/growth stimulation expressed gene 2 （ST2）/interleukin-1 receptor accessory protein （IL-1RAP） signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst， according to the previous network pharmacology results， this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways， components， and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently， a rat model of ovalbumin （OVA）-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups： Control， model， low-dose QDYF （QDYF-L， 4.04 g·kg^-1）， medium-dose QDYF （QDYF-M， 8.08 g·kg^-1）， high-dose QDYF （QDYF-H， 16.16 g·kg^-1）， and loratadine （0.9 mg·kg^-1）. After 14 days of intervention， behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin （HE） staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction （CVF）. The expression of E-cadherin （E-cad） in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 （Th2） cytokines interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） as well as helper T cell 1 （Th1） cytokines interleukin-2 （IL-2） and interferon-γ （INF-γ） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of transforming growth factor-beta 1 （TGF-β₁）， IL-33， ST2， and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33， ST2， and IL-1RAP had strong binding ability with the main active ingredients—wogonin， 7-methoxy-2-methylisoflavone， formononetin， naringenin， stigmasterol， and beta-sitosterol of QDYF， with the binding energy < -4.25 kcal⋅mol^-1（1 cal≈4.184 J）. The results of in vivo experiments showed that compared with the control group， the model group exhibited increased behavioral scores （P<0.05）， aggravated pathological damage of nasal mucosa， increased collagen fiber deposition and CVF （P<0.05）， elevated serum levels of IL-4， IL-5， and IL-13， up-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）， down-regulated expression of E-cad， and declined serum levels of IL-2， IFN-γ， and IFN-γ/IL-4 ratio （P<0.05）. Compared with the model group， the QDYF groups and loratadine group showed reduced behavioral scores （P<0.05）， alleviated pathological damage of nasal mucosa， reduced collagen fiber deposition and CVF （P<0.05）， and up-regulated E-cad expression （P<0.05）. Compared with the model group， the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio （P<0.05）， declined serum levels of IL-4， IL-5， and IL-13， and down-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）. In addition， the QDYF-H group exhibited an elevated serum IL-2 level （P<0.05）. The QDYF-M group showed down-regulated protein levels of TGF-β₁， IL-33 and IL-1RAP in the nasal mucosa （P<0.05）. The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa （P<0.05）. ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway， thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.

ObjectiveTo investigate the effects of three-dimensional foot-ankle exercises (3DFAE) on mild-to-moderate hallux valgus in young women. MethodsFrom October to December, 2024, 45 female patients aged 18 to 26 years with hallux valgus were recruited from Capital University of Physical Education and Sports. They were randomly divided into control group (n = 15), toe-spread-out (TSO) group (n = 15) and 3DFAE group (n = 15). The control group only received foot health education, while the two intervention groups performed corresponding exercise training, for four weeks. Hallux valgus angle (HVA) was measured with photographic method, abductor hallucis activation was detected with surface electromyography, cross-sectional area of abductor hallucis was measured with Doppler ultrasound, and active ankle dorsiflexion range of motion (ROM) was assessed with a goniometer, before intervention, immediately after intervention, and four weeks after training cessation. A perceived difficulty scale was adopted to evaluate the training difficulty of TSO group and 3DFAE group at the first training session and upon completion of intervention. ResultsThe effects of time and interaction were significant for bilateral HVA, abductor hallucis activation, cross-sectional area of abductor hallucis and ankle dorsiflexion ROM (F > 2.728, P < 0.05), and the effect of group of left ankle dorsiflexion ROM was also significant (F = 4.995, P < 0.05). After intervention, bilateral HVA, abductor hallucis activation, cross-sectional area of abductor hallucis and ankle dorsiflexion ROM were all better than those before intervention (P < 0.05), and most indicators were superior to those measured at the 4-week follow-up (P < 0.05). The left ankle dorsiflexion ROM was better in 3DFAE group than in the control group and TSO group (P < 0.05). At the first intervention session, the perceived training difficulty was lower in 3DFAE group than in TSO group (t = 3.334, P = 0.002), and it decreased (t = 5.292, P < 0.001) after four weeks of training in TSO group, with no significant difference compared with 3DFAE group (P > 0.05). Conclusion3DFAE can improve ankle dorsiflexion ROM in young female patients with hallux valgus, with no more difficulty than TSO, and lower initial operation difficulty.

Objective: To investigate the epidemiological characteristics of epidemic encephalitis B in Huzhou City, Zhejiang Province from 2007 to 2023, so as to provide the evidence for formulating prevention and control measures for epidemic encephalitis B. Methods: Epidemic encephalitis B case data in Huzhou City from 2007 to 2023 were collected through the National Notifiable Disease Reporting System of the Chinese Disease Prevention and Control Information System. The temporal, regional and population distribution characteristics of laboratory-confirmed epidemic encephalitis B cases were analyzed using the descriptively epidemiological method. Results: A total of 49 laboratory-confirmed epidemic encephalitis B cases were reported in Huzhou City from 2007 to 2023, and the average annual incidence was 0.10/105, showing a significant downward trend (P<0.05). The epidemic encephalitis B cases were concentrated from July to August, and July was the peak month, with 40 cases accounting for 81.63%. There was a statistically significant difference in the average annual incidences of epidemic encephalitis B among counties (districts) (P<0.05). Nanxun District had the highest reported incidence, with an average annual incidence of 0.23/105. There were 30 male cases and 19 female cases, with a male-to-female ratio of 1.58∶1. The youngest case was 5 months old, and the oldest was 49 years old. The children under 15 years were in the majority, with 42 cases accounting for 85.71%. Most of the cases were scattered children, with 25 cases accounting for 51.02%. There were 22 cases with no vaccination history and 21 cases with an unknown vaccination history, accounting for 44.90% and 42.86% respectively. All cases presented with fever. Other main clinical symptoms included listlessness, drowsiness, vomiting and headache, with 47, 40, 33 and 29 cases respectively, accounting for 95.92%, 81.63%, 67.35% and 59.18%, respectively. Conclusions The incidence of epidemic encephalitis B in Huzhou City remained at a relatively low level from 2007 to 2023, with Nanxun District being the high-risk area and July being the peak month for disease incidence. Fever and listlessness were the predominant clinical manifestations. Strengthening vaccination for children under 15 years should be prioritized.

On August 24 2024, Xiaoshan District Center for Disease Control and Prevention, Hangzhou City, received a report of two cases of varicella infection among staff in the intensive care unit (ICU) of a hospital in its jurisdiction. The center immediately organized personnel to conduct an epidemiological investigation of the cases and their close contacts. The index case was a patient admitted to the ICU who had large areas of red rash and pustules on the chest, back, and right axilla. This case was diagnosed with herpes zoster by a dermatology consultation within the hospital. The other nine secondary cases were all nursing staff in the ICU, who were clinically diagnosed with varicella between August 21 and September 1, with an attack rate of 14.06%. All secondary varicella cases had a history of contact with the herpes zoster case and no history of varicella infection. Their varicella vaccination history was unknown. Based on the results of the on-site epidemiological and sanitary investigations, it was determined that this was an outbreak of varicella in the hospital caused by a herpes zoster case. After the last case was diagnosed, no new cases were reported within the longest incubation period (21 days), and the outbreak was declared over on September 21. Close contact with the herpes zoster case was likely the main cause of the outbreak. This highlights the need for early identification and isolation of suspected herpes zoster cases in hospitals in the future, as well as enhanced protective measures to prevent nosocomial infections.

Objective: To investigate the epidemiological characteristics of pertussis in Harbin City from 2015 to 2024, so as to provide the basis for formulating pertussis prevention and control measures. Methods: The incidence data of pertussis in Harbin City from 2015 to 2024 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System, and the vaccination data were collected through the Immunization Program Information System of Heilongjiang Province. Descriptive epidemiological methods were used to analyze the temporal, regional and population distribution characteristics of pertussis incidence as well as the immunization history of pertussis cases. Results: A total of 417 cases of pertussis were reported in Harbin City from 2015 to 2024, with an average annual reported incidence of 0.41/100 000. The reported incidence increased from 0.18/100 000 in 2015 to 0.64/100 000 in 2024, showing an overall upward trend (P<0.05). The peak incidence period was from August to November, with 253 cases, accounting for 60.67%. The average annual reported incidences of pertussis in Shuangcheng District, Nangang District and Daoli District were relatively high, at 1.09/100 000, 0.93/100 000 and 0.52/100 000, respectively. There were 223 male cases and 194 female cases, with a male-to-female ratio of 1.15∶1. The average annual reported incidence of pertussis was 0.45/100 000 in males and 0.39/100 000 in females, with no statistically significant difference (P>0.05). Cases were predominantly distributed among children under 6 months and those aged 6 to under 10 years, with 176 and 144 cases, accounting for 42.21% and 34.53% respectively. The majority of cases were scattered children, with 266 cases (63.79%). There were 175 cases (41.97%) without diphtheria-tetanus-pertussis (DTP) vaccine and 172 cases (41.25%) who had completed the full course of immunization. Conclusions The incidence of pertussis in Harbin City showed an upward trend from 2015 to 2024. Autumn was identified as the peak season for disease onset. Shuangcheng District and Nangang District were the high-incidence areas. Children under 6 months, those aged 6 to under 10 years, scattered children, and those who had not received the DTP vaccine were the high-risk groups. It is recommended to improve pertussis surveillance strategies and strengthen childhood immunization programs.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny