Objective: To investigate the moderating effect of health literacy on the association between insomnia and non suicidal self injury (NSSI) behaviors among college freshmen, so as to provide evidence for improving interventions targeting NSSI behaviors. Methods: A longitudinal survey was conducted among 5 615 college freshmen selected from three colleges in Hefei, Huainan and Anqing cities of Anhui Province by cluster sampling (T0:May-June 2024; T1:October-December 2024). The Chinese version of the Insomnia Severity Index, Chinese Adolescent Interactive Health Literacy Questionnaire, and Adolescent Non suicidal Self injury Assessment Questionnaire were used to assess students insomnia, health literacy, and NSSI behaviors, respectively. Between group comparison was performed with the Chi square test, and the PROCESS macro (Model 1) was used to analyze the moderating role of health literacy in the association between insomnia and NSSI, and simple slope analysis was employed to further elucidate the pattern of the moderating effect. Results: The report rate of NSSI behaviors among college freshmen was 2.96 % at T1. The detection rate was significantly higher among boys, students with poorer family economic status, those with fewer close friends and those who were only children than in the corresponding comparison groups, with all differences statistically significant ( χ 2=5.13-39.56, all P <0.05). The results of the moderation analysis indicated that insomnia at T0 positively predicted NSSI behaviors at T1 among college freshmen ( OR=1.44, 95%CI =1.22-1.69), whereas health literacy at T0 negatively predicted NSSI behaviors at T1 ( OR=0.73, 95%CI =0.62-0.86); the interaction term of the two also significantly predicted NSSI behaviors ( OR=1.16, 95%CI =1.03-1.30) (all P <0.05). At low levels of health literacy, insomnia at T0 showed a positive predictive effect on NSSI behaviors at T1 ( B=0.22, 95%CI =0.06-0.38); at high levels of health literacy, the positive predictive effect of insomnia at T0 on NSSI behaviors at T1 remained statistically significant ( B=0.51, 95%CI =0.28-0.74) (both P <0.05). Conclusions Health literacy plays a significant positive moderating role in the association between insomnia and NSSI behaviors among college freshmen. NSSI behaviors interventions should address health cognition problems while enhancing individuals health literacy.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

In October 2024, a 36-year-old female patient with botulinum toxin type A intoxication for 15d was admitted to the Department of Neurology of Northern Jiangsu People’s Hospital. Although type A botulinum antitoxin (BAT) therapy remained effective, the patient developed a serum sickness-like reaction (SSLR) on day 4 of treatment after receiving eight consecutive desensitizing intramuscular injections of BAT. After stopping the injection of the drug and giving intravenous dexamethasone, the patient’s symptoms improved. On the 6th day after stopping the injection of botulinum antitoxin type A, the patient was followed up in the outpatient clinic and the skin symptoms had almost disappeared. This article analyzed the patient’s medical records and explored the association between BAT and SSLR, suggesting that medical personnel should be alert to the risk of adverse reactions when applying antitoxin therapy, and that they should identify and intervene in a timely manner in order to ensure the safety of the medication and therapeutic efficacy of the patients.

Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective:To compare the efficacy of gasless robotic surgery via transaxillary approach and combined axillary-retroauricular approach for unilateral N1b PTC, and to explore the safety and effectiveness of gasless robotic surgery via transaxillary approach for unilateral N1b PTC. Methods:Unilateral N1b PTC patients who underwent surgery in the Department of Otolaryngology, Sun Yat Sen Memorial Hospital, Sun Yat sen University between July 2016 and December 2024 were included and analyzed. According to the inclusion and exclusion criteria and the differences of surgical approaches, the patients were divided into the transaxillary approach（TA） group and the combined axillary-retroauricular approach（TARA） group. The demographic data, operation time, intraoperative blood loss, postoperative drainage volume, postoperative complications, shoulder function evaluation, postoperative visual analogue scale（VAS） of neck aesthetics and recurrence of the two groups were statistically analyzed. Results:A total of 88 patients undergoing gasless robotic surgery were included in this study, including 23 cases in the TA group and 65 cases in the TARA group. The proportion of males in the TA group was significantly higher than that in the TARA group（56.5% vs 21.5%, χ²=9.776, P=0.002）. The total operation time in the TA group was significantly lower than that in the TARA Group（180.00[155.00, 220.00]min vs 220.00[177.50, 272.50]min, z=-2.775, P=0.006）, and the postoperative blood loss in the TA group was significantly lower than that in the TARA Group（30.00[20.00, 50.00]ml vs 50.00[30.00, 60.00]ml, Z=-2.127, P=0.033）. The proportion of area Ⅱ-Ⅴ in the TA group and the TARA group was 87.0% and 70.8%, respectively, and there was no significant difference between the two groups（P>0.05）. There was no significant difference in lateral cervical lymph node dissection and central lymph node dissection between the two groups（P>0.05）. During the follow-up period, no recurrence was found in the two groups, and there was no significant difference in the incidence of complications between the two groups（P>0.05）. According to the stratification of dynamic recurrence risk assessment, it can be seen that the proportion of curative effect satisfaction in the TA group was as high as 95.7%, and that in the TARA group was as high as 81.5%, with no significant difference between the two groups. There was no significant difference in VAS score of neck, Constant Shoulder Score and NDⅡ scale between the two groups（P>0.05）. Conclusion:Gasless robotic surgery via transaxillary approach for unilateral N1b PTC is safe and feasible, and the amount postoperative lymph node acquisition is equivalent to that of combined axillary-retroauricular approach, which can provide a new choice for the treatment of unilateral N1b PTC patients.
Humans ; Robotic Surgical Procedures/methods* ; Axilla/surgery* ; Male ; Female ; Operative Time ; Middle Aged ; Adult ; Treatment Outcome ; Postoperative Complications

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective:To conduct a latent profile analysis of general self-efficacy among postpartum nurses with two children and explore the influencing factors of different profiles.Methods:A stratified sampling approach was used to recruit 298 clinical nurses with two children who had resumed work from 12 public healthcare facilities in Mianyang during May and December 2023. Data were collected using a demographic questionnaire, Work-Family Conflict Scale, Nursing Stress Scale, Family Stress Scale, and General Self-Efficacy Scale. Latent profile analysis was performed via Mplus 8.3. Pearson correlation and logistic regression analyses were used to examine associations between self-efficacy, work-family conflict, nursing stress, family stress, and profile membership.Results:Data collection yielded 298 questionnaires, with 281 valid responses (94.3% response rate). Three latent profiles of general self-efficacy were identified: low efficacy group (43.8%), moderate efficacy group (42.7%), and high efficacy group (13.5%). Work position, hospital level, time since return to work, nursing stress, and family stress were significant predictors of profile membership ( P< 0.05) . Conclusions:General self-efficacy among nurses with two children post-childbirth is heterogeneous. Nursing administrators should deliver tailored interventions based on latent profile characteristics and develop individualized self-efficacy enhancement programs from both individual and organizational perspectives to improve adaptability and competency during post-return work transition.