Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To compare the efficacy of dienogest (DNG) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of intrinsic and extrinsic subtypes of adenomyosis.Methods:Totally 232 patients were enrolled in the study who were diagnosed as adenomyosis by ultrasound or pelvic magnetic resonance imaging (MRI), and were classified into intrinsic and extrinsic subtypes according to different locations of lesions in MRI, treated with DNG (DNG group) or LNG-IUS (LNG-IUS group) in Peking University Third Hospital from July 2019 to December 2023. Clinical data of patients were retrospectively collected to analyze the clinical and imaging characteristics of different MRI subtypes of adenomyosis and whether there were differences in the therapeutic effects of DNG and LNG-IUS.Results:(1) Among the 232 patients enrolled, 129 were intrinsic subtype and 103 were extrinsic subtype. Among the 129 patients treated with DNG, the numbers of intrinsic and extrinsic subtype were 69 and 60, respectively. And among the 103 patients treated with LNG-IUS, the numbers of intrinsic and extrinsic subtype were 60 and 43, respectively. The mean age in DNG group [(37.5±5.6) years] was lower than that in LNG-IUS group [(40.3±4.3) years, P<0.001]. There were no significant differences in other clinical features (all P>0.05). (2) The visual analog scale (VAS) scores of dysmenorrhea and cancer antigen 125 (CA 125) levels in DNG group and LNG-IUS group were significantly decreased after treatment (all P<0.001), and hemoglobin levels were increased (both P<0.01). Compared between the two groups, the VAS score after treatment was lower in DNG group ( P<0.001), and the hemoglobin level was increased more significantly in DNG group ( P=0.016). The complete remission rates of dysmenorrhea in DNG group and LNG-IUS group were 73.0% (89/122) and 29.5% (28/95), respectively ( P=0.039). The incidence of irregular bleeding in DNG group was higher than LNG-IUS group, but there was no statistical significance [62.8% (81/129) vs 52.4% (54/103), P=0.112]. (3) Among patients with intrinsic adenomyosis, the incidence of menorrhagia was significantly higher than in those with extrinsic adenomyosis ( P<0.001), while the incidence and severity of dysmenorrhea were lower compared to extrinsic adenomyosis ( P=0.004, P=0.007, respectively). After treatment with DNG and LNG-IUS, there were no statistically significant differences in VAS scores between patients with intrinsic and extrinsic adenomyosis (all P>0.05). The incidence of irregular bleeding after DNG treatment was 78.3% (54/69) in intrinsic adenomyosis, which was higher than the 45.0% (27/60) observed in extrinsic adenomyosis ( P<0.01). Similarly, the incidence of irregular bleeding after LNG-IUS treatment was 63.3% (38/60) in intrinsic adenomyosis, higher than the 37.2% (16/43) in extrinsic adenomyosis ( P=0.009). (4) DNG treatment ( OR=19.163, 95% CI: 7.564-48.544; P<0.01) and duration of treatment ( OR=1.043, 95% CI: 1.012-1.075; P=0.007) were independent positive factors for complete remission of dysmenorrhea, while VAS score before treatment ( OR=0.654, 95% CI: 0.454-0.942; P=0.023) was negative factor. Intrinsic subtype was an independent risk factor for irregular bleeding ( OR=0.436, 95% CI: 0.235-0.811; P=0.009). Conclusions:DNG demonstrates greater advantages over LNG-IUS in terms of complete relief of dysmenorrhea and the degree of symptom alleviation. The incidence of irregular vaginal bleeding in patients with intrinsic adenomyosis is higher than in those with extrinsic adenomyosis. For patients with extrinsic adenomyosis, particularly those with prominent dysmenorrhea symptoms, DNG treatment offers greater benefits. However, for patients with intrinsic adenomyosis and those with significant menstrual disorders, a more cautious approach is required when selecting progestin therapy, along with enhanced monitoring and management.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

Objective:To report the preliminary clinical exploration result of spatially fractionated radiation therapy (SFPT) using the pencil-beam-scanning (PBS) technique at a single center for the treatment of patients with bulky tumors.Methods:Data on the clinical characteristics, tumor characteristics, and dosimetric parameters were retrospectively collected from patients with bulky tumors at the Radiation Oncology Department, Ion Medical Center, First Affiliated Hospital of University of Science and Technology of China (i.e., the Hefei Ion Medical Center) from April 2024 to December 2024. Three-dimensional lattice radiotherapy (LRT) was primarily utilized in the SFRT, with multi-field robust optimization performed using pencil beam scanning. SFRT target volumes (STVs) were defined as 1.0 cm-diameter spheres. Primary observation indicators included the remission rate of tumor-associated symptoms, followed by the local tumor control rate.Results:A total of 12 patients were enrolled in this study, with a median age of 61 years (28-85 years). The primary tumors included hepatocellular carcinoma (six patients), sarcomas (three patients), and lung cancer (two patients). Eight patients received concurrent systemic therapy. The SFRT plans showed a median gross tumor volume (GTV) of 429.63 cm 3 (120.60-2 053.30 cm 3), a median STV number of 8 (3-20), a single-fraction dose to STVs of 10 GyE, a median irradiation quantity of 6 (3-8), a median STV of 8 cm 3 (3-20 cm 3), a median STV proportion of 2.09% (0.62%-3.30%), a median GTV corresponding to a single STV of 52.91 cm 3 (30.25-159.82 cm 3), and a median peak-to-valley dose ratio of 3.37 (2.29-7.60). All patients received conventionally fractionated proton therapy (CFPT), with a median prescription dose of 50 GyE (40-60 GyE). Furthermore, these patients showed a median follow-up time of 174 d (133-235 d), a remission rate of tumor-associated symptoms of 75%, and a local control rate of 100%. Four patients experienced grade 1-2 treatment-related adverse events, suggesting high overall tolerability of the patients. Conclusions:SFRT represents a promising technique with high control rates and tolerability for bulky tumors, providing the possibility for quick symptom relief and the control of tumor progression.

Objective To compare the therapeutic efficacy of sequential therapy with gonadotropin releasing hormone agonist(GnRH-a)combined with dienogest(DNG)versus DNG alone in patients with adenomyosis.Methods A retrospective analysis was conducted on clinical data from 129 patients diagnosed with adenomyosis by ultrasound and MRI between August 2020 and December 2023.Among them,60 patients received sequential therapy with GnRH-a followed by DNG(combination group)and 69 patients received DNG monotherapy(monotherapy group).There were no significant differences in baseline characteristics,including age,incidence of dysmenorrhea,incidence of menorrhagia,uterine volume,and type of adenomyosis between the two groups(P>0.05).The combination group received subcutaneous injections of leuprorelin3.75 mg every28 d for3 to 6 cycles,followed by oral DNG 2 mg/d for more than 3 months.The monotherapy group received oral DNG 2 mg/d alone for more than 3 months.Treatment outcomes and adverse reactions were compared between the two groups.Results The median duration of DNG treatment was 16.0(10.2,26.0)months in the combination group and13.0(6.0,23.0)months in the monotherapy group.The difference between the two groups was not statistically significant(Z=-1.587,P=0.113).Both groups showed a significant reduction in dysmenorrhea as measured by the Visual Analogue Scale(VAS)score,a significant decrease in serum CA125 levels,and a significant increase in hemoglobin levels after treatment compared to before treatment(all P<0.001).There were no significant differences between the two groups(P>0.05).Regarding uterine volume,the combination group showed a trend toward reduction after treatment[146.3(77.6,250.4)cm3 vs.118.4(82.4,233.4)cm3,Z=0.272,P=0.785],while the monotherapy group showed a significant increase in uterine volume compared to before treatment[162.9(110.8,256.0)cm3 vs.187.6(123.7,276.2)cm3,Z=2.945,P=0.003].The incidence of irregular vaginal bleeding in the combination group[50.0%(30/60)]was lower than that in the monotherapy group[75.4%(52/69),χ2=8.914,P=0.003].Conclusions Both sequential therapy with GnRH-a combined with DNG and DNG monotherapy are effective in relieving dysmenorrhoea,reducing CA125 levels,and increasing hemoglobin levels in patients with adenomyosis.However,sequential therapy is associated with a lower incidence of irregular vaginal bleeding compared to monotherapy and demonstrates a potential advantage in controlling uterine volume growth.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Cognitive frailty, as one of the independent dimensions of frailty syndrome, has received increasing attention from researchers in recent years. Cognitive frailty not only reduces the quality of life for elderly people, but also increases the risk of adverse outcomes such as falls, disabilities, hospitalization, dementia, and death. This article introduces the concept, assessment methods, influencing factors, and intervention measures of cognitive frailty, emphasizing the important role of general practitioners in screening and management of cognitive frailty.