Repeat expansion diseases(REDs) are a group of genetic disorders caused by the pathological expansion of specific short tandem repeats(STRs) in genomic DNA. They are characterized by significant clinical and genetic heterogeneity. Owing to the complexity of their pathogenesis, effective treatments remain elusive. With the in-depth analysis of the pathogenesis of these diseases, along with the development and innovation of targeting tools in recent years, targeted therapy strategies have become a research hotspot, and some antisense oligonucleotide drugs have entered the clinical trial stage. This article aims to review the latest advances in basic research and clinical trial outcomes of targeted therapy at the DNA, RNA and protein levels. Currently, this field still faces key bottlenecks including a high risk of off-target effects, low delivery efficiency, and challenges in clinical translation. Future efforts should focus on the optimization and refinement of targeting tools and delivery vectors, as well as multilevel collaborative combination therapeutic strategies.Combined with precise clinical classification and staging, this will promote the fundamental transformation of REDs treatment from symptomatic supportive care to etiological intervention.

With the rapid development and widespread application of microwave technology,people's lives and work have been made more convenient.However,the health of those who are constantly exposed to complex microwave environments is also threatened.In recent years,many studies have found that long-term exposure to micro waves can cause damage to cognitive function.However,the damage mechanism has not been fully understood.This article reviews the research progress of microwave radiation on cognitive function in recent years,the damage mechanism,and the related drugs for protection and treatment,in order to provide references for research in this field.

Endometrial injury diseases are an important factors in female infertility, reduced menstruation, and adverse pregnancy outcomes. Clinical characteristics include intrauterine adhesions, a thin endometrium, and reduced endometrial receptivity. Restoring the morphology of the uterine cavity and promoting endometrial reconstruction are the main goals of treatment. At present, hormone medication and surgery are the major Western medicine treatments. Traditional Chinese Medicine has an advantage in treating endometrial injury and preventing postoperative recurrence. Traditional Chinese Medicine diagnosis focuses on "kidney deficiency" as the primary condition,"blood stasis" as the secondary condition, and combined with "liver depression". Therapeutic strategies aim to "replenish kidney""nourish blood""dispel blood stasis", and improve the endometrium. By means of combination of disease and syndrome, classical prescription addition and subtraction, clinical effective experience, combination of acupuncture and medicine and external treatment of Traditional Chinese Medicine can improve the effect and prognosis of patients with endometrial injury diseases. This article reviews the progress of combined Traditional Chinese and Western Medicine treatment of endometrial injury diseases to provide reference for its clinical treatment.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

Objective:To understand the burden of chronic kidney disease (CKD) and its risk factors in Fujian Province during 1990-2019.Methods:Based on the Global Burden of Disease Study 2019, the incidence rate, mortality rate and disability-adjusted life years (DALYs) of CKD in Fujian from 1990 to 2019 were calculated. An age-period-cohort model was used to estimate the effects of age, period, and cohort on age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of CKD. Comparative risk assessment theory was used to calculate the potential attributable DALYs due to risk factors.Results:In 2019, the ASIR of CKD in Fujian exceeded the national average. The ASIR of CKD showed an increasing trend from 1990 to 2019, but the ASMR and ASDR of CKD exhibited decreasing trends during the same period. In 2019, the ASIR of CKD was higher in women than in men, while the ASMR and ASDR were higher in men than in women. Age-period-cohort analysis indicated that ASIR, ASMR, and ASDR of CKD increased with age. The period effect for ASIR decreased first before increase, while the period effect for ASMR and ASDR displayed fluctuating trends. The cohort effect showed an upward trajectory for ASIR, but a stable status before downward trajectories for ASMR and ASDR. Compared with 1990, except the increase in the ASDR of CKD attributed to high BMI and high temperatures, the ASDR of CKD attributed to other risk factors all showed decreases in 2019. However, the ASDR attributed to high sodium intake remained higher compared with the global average.Conclusion:The burden of CKD remains heavy in Fujian, and it is necessary to reduce the attributable risk factors, such as high sodium intake and high BMI, to address this problem.

Objective:To investigate clinical characteristics of immunocompromised individuals with herpes zoster.Methods:A retrospective study was conducted on 78 immunocompromised patients with herpes zoster hospitalized at Zhongda Hospital affiliated to Southeast University from January 2016 to December 2023, and these patients were assigned to the observation group. During the same period, 78 immunocompetent inpatients with herpes zoster matched (1∶1 ratio) by age and admission time served as a control group. General data, clinical manifestations, and laboratory findings (including blood routine test, liver and kidney function, and inflammatory markers) were compared between the two groups.Results:In the observation group, there were 27 males and 51 females, with the age being 65.76 ± 14.47 years; the main causes of immunocompromise in this group were solid tumors (47 cases, 60.26%) and hematologic tumors (7 cases, 8.97%) ; 26 (33.33%) patients with autoimmune diseases were treated with prednisone at a dose of ≥ 10 mg/d for more than 2 weeks. In the control group, there were 35 males and 43 females, with the age being 67.73 ± 13.89 years. No significant differences were found between the two groups in terms of gender, age, time from the onset of rashes or pain to hospitalization, time to lesion healing, the order of appearance of pain and rashes, the affected side of the body, or the proportion of patients with disseminated herpes zoster (all P > 0.05). However, there was a significant difference in the distribution of affected nerve segments between the two groups ( P = 0.013) ; the main affected nerves were the thoracic and brachial nerves (34 cases, 43.59%) and the lumbosacral nerves (29 cases, 37.18%) in the observation group, while the lumbosacral nerves (31 cases, 39.74%) and cranial-cervical nerves (25 cases, 32.05%) were more commonly affected in the control group. The skin lesions in both groups mainly manifested as blisters, pustules and/or hemorrhagic blisters, and the proportion of patients with pustules and/or hemorrhagic blisters was significantly higher in the observation group (25 cases, 32.05%) than in the control group (11 cases, 14.10%; χ2 = 7.08, P = 0.008). The observation group showed a significantly higher proportion of patients with fever (24 cases, 30.77%), frequency of oral analgesic use during hospital stay [2.00 (1.26, 2.33) times/day], and recurrence rate (6 cases, 7.69%) compared with those in the control group (13 cases, 16.67%; 1.43 [1.00, 2.00] times/day; 0, respectively). Additionally, the observation group exhibited significant increases in several parameters compared with the control group, including the proportions of patients with anemia (27 cases [34.62%] vs. 6 cases [7.69%]), kidney function abnormalities (9 cases [11.54%] vs. 2 cases [2.56%]), elevated alanine aminotransferase/aspartate aminotransferase ratios, increased erythrocyte sedimentation rates, and with elevated C-reactive protein levels, as well as those with decreased white blood cell counts, albumin levels, prealbumin levels, and with CD8 + T cell counts (all P < 0.05). In terms of novel inflammatory markers, the observation group showed significantly increased neutrophil/lymphocyte ratios, red blood cell distribution width/hemoglobin ratios, and C-reactive protein/albumin ratios, but significantly decreased albumin/fibrinogen ratios and platelet/neutrophil ratios compared with the control group (all P < 0.05) . Conclusion:Compared with the immunocompetent patients with herpes zoster, the immunocompromised patients with herpes zoster showed poorer cell-mediated immunity, more complex clinical manifestations, more severe systemic inflammatory responses, more pronounced pain, and higher likelihood of recurrent herpes zoster.

Anxiety is a major emotional disorder manifested in the individual's expectation of future threats.The incidence rate of anxiety is about 7.3％,with the highest lifetime prevalence rate among mental health conditions.The mechanism of anxiety overlaps with depression,and anxiety is a typical symptom of various mental diseases or emotional disorders in traditional Chinese medicine.The high rates of comorbidity and disability pose serious threats to people's health.Animal models are important tools for studying anxiety and are of great use for deciphering the pathogenesis of anxiety and for developing drugs.The traditional paradigm of stress-induced anxiety,however,is relatively limited.Based on traditional theory combined with clinical and animal experimental data,we propose a new hypothesis of"insufficiency of ZhiYi'causing anxiety,defined as"an anxiety state induced by the inability of an individual to meet their own needs,limited or lacking after multiple attempts,rendered hindered and powerless by an inability to meet their desires".This hypothesis is more in line with the typical manifestations of despair,lack of pleasure,and social withdrawal in clinical patients,and is supported by traditional theory and experimental data showing"hunger but unable to eat,food but unable to obtain,and gain but not full".Based on this,the established modeling paradigm is easy to apply,with good repeatability and low cost,and can be used to establish anxiety models in rats and mice,to provide a theoretical and model basis for the development and pharmacological evaluation of anti-anxiety drugs.

OBJECTIVES: Depression is a common negative emotion that can significantly impact physical and mental health. Due to their occupational characteristics, medical staff are more susceptible to depression compared to the general population. This study aims to explore the influence of future-oriented coping on depression among medical staff and the mediating roles of psychological resilience and perceived stress, providing theoretical guidance for depression intervention strategies in this group. METHODS: A cross-sectional survey was conducted among medical staff at a tertiary hospital using convenience sampling. Data were collected via the "Wenjuanxing" platform. A total of 754 questionnaires were distributed; after excluding invalid responses (e.g., duplicate IPs or insufficient completion time), 655 valid questionnaires were retained (valid response rate: 86.87%). Instruments included a demographic questionnaire, the Future-Oriented Coping Scale, the Connor-Davidson Resilience Scale, the Perceived Stress Scale, and the Self-Rating Depression Scale. All scales demonstrated high internal consistency (Cronbach's α>0.88) and validity. SPSS 27.0 was used for descriptive analysis, and PROCESS macro (Model 6) was used to test the chain mediation model. Harman's one-factor test was applied to control for common method bias. RESULTS: Descriptive analyses showed that future-oriented coping was positively correlated with psychological resilience and negatively correlated with perceived stress and depression. Mediation analysis revealed that future-oriented coping significantly predicted lower depression levels among medical staff (β=-0.283, P<0.001). Psychological resilience partially mediated the relationship (effect size=-0.329, accounting for 34.13% of the total effect), as did perceived stress (effect size=-0.099, 10.27%). A significant chain mediation path was identified: "future-oriented coping → psychological resilience → perceived stress → depression" (effect size=-0.253, 26.24%). The total indirect effect accounted for 70.64% of the overall effect, highlighting the substantial role of the mediating pathways. CONCLUSIONS Future-oriented coping can reduce depressive symptoms in medical staff, with psychological resilience and perceived stress serving as key mediators in a chain structure. These findings suggest that enhancing future-oriented coping strategies and psychological resilience may improve stress adaptation and reduce depression levels in this population.
Humans ; Adaptation, Psychological ; Resilience, Psychological ; Cross-Sectional Studies ; Depression/psychology* ; Surveys and Questionnaires ; Stress, Psychological/psychology* ; Male ; Female ; Adult ; Middle Aged ; Medical Staff/psychology* ; Occupational Stress/psychology*

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P＜0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P＜0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P＜0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P＜0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P＜0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P＜0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.