ObjectiveTo evaluate the clinical efficacy of acupuncture in the treatment of adolescent depression and to explore its potential mechanisms based on functional magnetic resonance imaging （fMRI） and serum proteomics. MethodsA randomized， double-blind， sham acupuncture-controlled trial design was conducted. A total of 100 adolescents with depression were enrolled and randomly assigned to an acupuncture group and a sham acupuncture group， with 50 participants in each group. In addition， 20 healthy subjects were recruited as healthy controls. Participants in the acupuncture group received acupuncture at Baihui （GV 20）， Yintang （GV 29）， Zhongwan （CV 12）， Qihai （CV 6）， bilateral Tianshu （ST 25）， bilateral Neiguan （PC 6）， bilateral Zusanli （ST 36）， and bilateral Taichong （LR3）. The sham acupuncture group received intervention using a blunt placebo needle without skin penetration. Both groups received 30-min treatments three times per week for 4 weeks. The primary outcome was the reduction rate of the 24-item Hamilton Depression Rating Scale （HAMD-24） score. Secondary outcomes included changes in HAMD-24 scores before and after treatment， covering nine factors （anxiety/somatization， cognitive impairment， sleep disturbance， psychomotor retardation， hopelessness， fatigue， weight change， diurnal mood variation， and suicidal ideation）， response rate and remission rate after treatment， and symptom severity before and after treatment. Subgroup analyses of total HAMD-24 scores were performed according to concomitant medication use and the number of medications taken. During the study period， all adverse events were monitored and recorded to evaluate safety. Patients who volunteered and met the eligibility criteria for imaging examinations were selected to undergo brain fMRI scanning and serum proteomic analysis to investigate changes in functional connectivity among brain regions and differential proteins. ResultsA total of 49 participants in the acupuncture group and 50 participants in the sham acupuncture group were included in the efficacy analysis. Among them， 20 participants in the acupuncture group and 21 in the sham acupuncture group completed fMRI scans， while 19 participants in the acupuncture group and 21 in the sham acupuncture group completed serum proteomic analyses. After 4 weeks of treatment， the mean reduction rate of HAMD-24 score in the acupuncture group was significantly higher than that in the sham acupuncture group ［（58±24）% vs.（26±19）%， P＜0.01］. Compared to baseline， scores for anxiety/somatization， cognitive impairment， psychomotor retardation， and hopelessness， and the total HAMD-24 score significantly decreased in both groups. In addition， the acupuncture group showed significant reductions in sleep disturbance， fatigue， and suicidal ideation scores （P＜0.01）. After treatment， the response rate and remission rate were 67.35% （33/49） and 24.48% （12/49） in the acupuncture group， respectively， significantly higher than 6.00% （3/50） and 0 in the sham acupuncture group （P＜0.01）. The proportion of participants with moderate symptoms was lower， whereas the proportion with mild symptoms was higher in the acupuncture group than the sham acupuncture group （P＜0.01）. Among those receiving acupuncture alone， acupuncture combined with medication， or fewer than three medications， the total HAMD-24 scores decreased after treatment in both the acupuncture subgroup and the sham acupuncture subgroup， with significantly lower scores in the acupuncture subgroup （P＜0.01）. During the study period， four mild adverse events were reported， including one case in the acupuncture group and three cases in the sham acupuncture group； none of these events affected the continuation of treatment. fMRI results showed that acupuncture enhanced functional connectivity between the prefrontal cortex and cerebellar-limbic system-related brain regions. Proteomic analysis identified 24 differentially expressed proteins associated with acupuncture treatment， mainly enriched in pathways related to neuroinflammation and energy metabolism. ConclusionAcupuncture can significantly improve depressive symptoms in adolescents with depression. Its therapeutic effects may be achieved by modulating emotion-related brain networks and regulating pathways associated with neuroinflammation and energy metabolism.

AIM:To investigate the dynamic changes in ocular surface function after eyelid malignant tumor resection combined with Hughes flap reconstruction.

METHODS:A prospective self-controlled study was conducted. Patients who underwent eyelid malignant tumor resection combined with Hughes tarsoconjunctival flap reconstruction(all tumors occured in the lower eyelid)at Shanxi Eye Hospital from January 2021 to December 2023 were enrolled. The contralateral healthy eye served as control. Ocular surface examinations were performed preoperatively and at 3, 6, 9, and 12 mo postoperatively, including ocular surface disease index(OSDI), tear meniscus height(TMH), non-invasive average tear film break-up time(NiaBUT), tear film lipid layer grading, upper and lower eyelid meibomian gland dropout grading, corneal fluorescein staining, and eye redness index.

RESULTS:A total of 36 patients were enrolled. Two patients were lost to follow-up because they did not complete the scheduled follow-up period, leaving 34 patients with complete data for analysis. The cohort comprised 10 men(29%)and 24 women(71%), with a mean age of 70.08±10.92 y(range 33-81 y). Histopathological diagnoses included basal cell carcinoma(BCC)in 22 eyes(65%), sebaceous gland carcinoma(SGC)in 10 eyes(29%), and squamous cell carcinoma(SCC)in 2 eyes(6%). Tumor size ranged from 4 to 30 mm(mean 12.64±0.31 mm). According to the AJCC staging system, 14 eyes(41%), 18 eyes(53%), and 2 eyes(6%)were classified as T1b, T2b, and T3b, respectively. Preoperatively, OSDI scores were higher in surgical eyes than in contralateral healthy eyes(28.74±13.72 vs 17.47±3.02, P<0.05). OSDI scores in surgical eyes further increased at 6, 9, and 12 mo postoperatively, peaking at 9 mo(all P<0.05), whereas no significant postoperative changes were observed in contralateral healthy eyes. Compared with contralateral healthy eyes, TMH in surgical eyes increased significantly at 3 mo postoperatively and remained elevated thereafter despite a slight decline(all P<0.05). NiaBUT in surgical eyes was shorter than the preoperative value from 3 mo postoperatively onward and was lower than that in contralateral healthy eyes(all P<0.05). Eye redness index in surgical eyes were consistently higher than those in contralateral healthy eyes(all P<0.001). Tear film lipid layer grade and meibomian gland dropout grades in both the upper and lower eyelids were significantly worsened postoperatively compared with baseline(all P<0.001). Corneal fluorescein staining grades were higher in surgical eyes than in contralateral healthy eyes preoperatively(P<0.001)and were higher at 3, 6, 9, and 12 mo postoperatively than at baseline(all P<0.001).

CONCLUSION: After lower eyelid malignant tumor resection combined with Hughes flap reconstruction, evaporative dry eye is the predominant phenotype. Meibomian gland dropout in both upper and lower eyelids appears irreversible within 12 mo postoperatively, and corneal epithelial damage and ocular surface inflammation persist over time.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

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

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:To conduct a symptom network analysis in patients with systemic lupus erythematosus (SLE) and identify core symptoms, in order to provide a foundation for the development of precision-based symptom management interventions.Methods:A convenience sampling method was used to recruit 420 SLE patients who received treatment at Shengjing Hospital of China Medical University between November 2022 and July 2023. The SLE Specific Symptom Checklist was administered to these patients. A contemporaneous symptom network was constructed using a Gaussian graphical model, and centrality measures including closeness centrality, betweenness centrality, and expected influence coefficient were calculated to determine the core symptoms within the network.Results:The most commonly reported symptoms among the 420 patients were fatigue (65.7%, 276/420), hair loss (59.8%, 251/420), photosensitivity (56.9%, 239/420), memory impairment (54.5%, 229/420), and facial swelling (52.1%, 219/420). In the symptom network analysis, the most central symptom was photosensitivity (closeness centrality=1.58; betweenness centrality=2.56; expected influence coefficient=1.06), followed by skin fragility (closeness centrality=1.00; betweenness centrality=0.43; expected influence coefficient=1.78), gastrointestinal discomfort (closeness centrality=1.30; betweenness centrality=1.14; expected influence coefficient=0.77), fatigue (closeness centrality=0.50; betweenness centrality=0.70; expected influence coefficient=1.61), and mood changes (closeness centrality=0.65; betweenness centrality=1.14; expected influence coefficient=0.89) .Conclusions:Among the various symptoms experienced by SLE patients, photosensitivity, skin fragility, gastrointestinal discomfort, fatigue, and mood changes emerged as core symptoms that influence and activate other symptoms in the network. Healthcare professionals should tailor symptom management strategies based on patients' self-reported symptom profiles, prioritize intervention targets, and work to reduce the overall symptom burden in individuals with SLE.

Objective:To conduct a symptom network analysis in patients with systemic lupus erythematosus (SLE) and identify core symptoms, in order to provide a foundation for the development of precision-based symptom management interventions.Methods:A convenience sampling method was used to recruit 420 SLE patients who received treatment at Shengjing Hospital of China Medical University between November 2022 and July 2023. The SLE Specific Symptom Checklist was administered to these patients. A contemporaneous symptom network was constructed using a Gaussian graphical model, and centrality measures including closeness centrality, betweenness centrality, and expected influence coefficient were calculated to determine the core symptoms within the network.Results:The most commonly reported symptoms among the 420 patients were fatigue (65.7%, 276/420), hair loss (59.8%, 251/420), photosensitivity (56.9%, 239/420), memory impairment (54.5%, 229/420), and facial swelling (52.1%, 219/420). In the symptom network analysis, the most central symptom was photosensitivity (closeness centrality=1.58; betweenness centrality=2.56; expected influence coefficient=1.06), followed by skin fragility (closeness centrality=1.00; betweenness centrality=0.43; expected influence coefficient=1.78), gastrointestinal discomfort (closeness centrality=1.30; betweenness centrality=1.14; expected influence coefficient=0.77), fatigue (closeness centrality=0.50; betweenness centrality=0.70; expected influence coefficient=1.61), and mood changes (closeness centrality=0.65; betweenness centrality=1.14; expected influence coefficient=0.89) .Conclusions:Among the various symptoms experienced by SLE patients, photosensitivity, skin fragility, gastrointestinal discomfort, fatigue, and mood changes emerged as core symptoms that influence and activate other symptoms in the network. Healthcare professionals should tailor symptom management strategies based on patients' self-reported symptom profiles, prioritize intervention targets, and work to reduce the overall symptom burden in individuals with SLE.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.