ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

Objective To develop a static progressive ankle stretcher for the treatment of functional disorders caused by scar contracture of the Achilles tendon after burn,and to evaluate its application effect.Methods The static progressive ankle stretcher was composed of a plantar support section and a calf support section,which was mainly made of a 3.2 mm-thick medical low-temperature thermoplastic plate,a commercially available 1 mm-diameter steel wire rope,grooved wheels,ice fishing reels with a diameter of about 50 mm,curved folding hinges and a locking threader with a hole diameter of about 1.5 mm.Totally 49 patients with scar contracture after deep Ⅱ to Ⅲ-degree burns of the Achilles tendon admitted to some hospital from March 2021 to January 2023 were prospectively selected and divided into a conventional rehabilitation group(25 cases)and a combined rehabilitation group(24 cases)using a randomized numerical table method.The patients in the conventional rehabilitation group underwent routine scar care such as anti-scarring medication application at home,scar massage,resistance training,joint loosening training in the hospital and compression therapy with the customized compression stockings/pants at the rest of the time,the patients in the combined rehabilitation group were treated with the static progressive ankle stretcher besides the measures taken for the conventional group.The two groups were compared in terms of scarring,ankle function and active dorsiflexion mobility of the ankle joint before and 12 weeks after the treatment,balance and walking ability 4 weeks and 12 weeks after the treatment,adverse events during the treatment and patient satisfaction 12 weeks after the treatment.SPSS 23.0 statistical software was used for data analysis.Results In terms of scarring condition,ankle function and active dorsiflexion mobility of the ankle joint all the patients were improved 12 weeks after the treatment,and the ones in the combined rehabilitation group behaved better than the ones in the conventional group,with the differences being statistically significant(P<0.05).The balance and walking ability 12 weeks after the treatment was better than that 4 weeks after the treatment in the two groups,and the combined rehabilitation group gained advantages over the conventional group in balance and walking ability,with the difference being statistically significant(P<0.05).During the treatment no adverse events due to the static progressive ankle stretcher were found,such as muscle tissue strain,scarred skin rupture,instrument friction and pressure injury.The combined rehabilitation group had higher patient satisfaction than the conventional group 12 weeks after the treatment,with the differences being statistically significant(P<0.05).Conclusion The static progressive ankle stretcher combined with the conventional rehabilitation treatment contributes to improving contracture scar conditions and joint mobility at the Achilles tendon area of the post-burn patients,which helps accelerate the recovery of ankle function after burns and enhance the balance and walking ability of the patients.[Chinese Medical Equipment Journal,2025,46(10):54-59]

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.

Pancreatic cancer is characterized by significant drug resistance,and despite continuous advancements in treatment regimens,the 5-year survival rate of patients remains low.The nuclear factor-κB(NF-κB)signaling pathway,frequently mutated in tumors,has been identified as a critical factor in triggering drug resistance.Multiple studies have demonstrated that strategies targeting NF-κB signaling transduction exhibit promising outcomes in pancreatic cancer treatment.Therefore,exploring the relationship between the NF-κB signaling pathway and drug resistance in pancreatic cancer has become a research hotspot in pancreatic cancer treatment.This review summarizes recent advances in the relationship between NF-κB signaling pathway and tumor drug resistance,as well as its role in pancreatic cancer treatment.Specifically,the mechanisms by which the NF-κB signaling pathway mediates drug resistance in pancreatic cancer are elaborated from two perspectives:chemotherapy and immunotherapy,aiming to provide insights for pancreatic cancer treatment and future research.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Objective To investigate the effects of estrogen signaling on T-cell recruitment and polarization in acutely injured skeletal muscle.Methods One hundred C57BL/6 male mice,one hundred and eighty C57BL/6 female mice were selected.Twenty-five female mice were ovariectomized(OVX)and 10 male mice were taken as the sham-operated(sham).Then,cardiotoxin(CTX)induced tibialis anterior(TA)injury for preparing mice myoinjury model.Subcutaneous injection of 17β-estradiol(E2)or estrogen receptor antagonist 4-hydroxytamoxifen(4-OHT)was performed.A total of 140 mice(70 males and 70 females)were divided into four group including:PBS-male,CTX-male,PBS-female,and CTX-female.Serum estradiol(E2)levels were measured by ELISA,and muscle injury models were validated via HE staining.Subsequently,20 male and 20 female mice were selected for immunofluorescence(IF)and Real-time PCR to assess estrogen receptors(ER)expression in injured muscle tissue.Further,10 male and 40 female mice were allocated into five experimental groups,including CTX,CTX+E2,CTX+4-OHT,CTX+OVX,CTX+sham.HE staining and IF were performed to evaluate inflammatory infiltration in the injured muscle.Additionally,50 female mice were divided into CTX and CTX+OVX groups,and IF combined with flow cytometry were used to analyze T-cell phenotypes and muscle fiber regeneration in the injured muscle.Results In vivo,serum E2 and myofiber ERβ increased post-injury in mice of both sexes,significantly higher in females.Compared to the control group,E2 alleviated inflammation,OVX exacerbated inflammation,increased CD4+T-cell infiltration,elevated T helper 1 cell(Th1)response,decreased regulatory T cells(Tregs),impaired regeneration.In vitro,IFN-γ/LPS significantly upregulated ERβ in myotubes.Conclusion Estrogen signaling critically regulates muscle inflammation.Estrogen deficiency(OVX)delays repair of skeletal muscle by promoting Th1 response and suppressing Tregs function.

Objective To explore the application effect of nursing intervention based on empow-erment theory in treatment of facial photoaging with fractional ablative fractional laser.Methods A total of 90 patients with facial photoaging who underwent fractional ablative fractional laser treatment were selected and divided into control group and observation group according to random number table method,with 45 cases in each group.The control group received routine nursing intervention,while the observation group received nursing intervention based on empowerment theory.The skin condi-tion,the incidence of adverse reactions,psychological state[Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS)]scores,and quality of life[Dermatology Life Quality Index(DLQI)]scores were compared between the two groups.Results After intervention,the percentages of skin characteristics such as enlarged facial pores,wrinkles,and spots in the observation group were higher than those in the control group;the incidence of adverse reactions in the observation group was lower than that in the control group(8.89％ versus 24.44％);the SAS scores,SDS scores,and total DLQI scores in the observation group were lower than those in the control group,with statistically sig-nificant differences(P＜0.05).Conclusion Nursing intervention based on empowerment theory can effectively improve the facial skin condition of patients with facial photoaging treated with fraction-al ablative fractional laser,reduce the incidence of adverse reactions,alleviate negative emotions,and enhance quality of life.

Shewanella oneidensis MR-1, a Gram-negative bacterium with a significant role in the adsorption and reduction of uranium in wastewater and a quorum-sensing effect, can be used to remove uranium from wastewater. Exogenous signaling molecules (acyl-homoserine lactones, AHLs) can be added to induce the quorum sensing behavior for rapid biofilm formation, thereby improving the removal efficiency of this bacterium for uranium. Extracellular polymeric substances (EPS), as the significant components of biofilm, play a key role in biofilm formation. To investigate the quorum sensing behavior induced by AHLs, we systematically investigated the effects of AHLs on the EPS secretion and biofilm properties of S. oneidensis MR-1 by regulating parameters such as AHL species, concentration, addition time point, and contact time. The results showed that the addition of 10 μmol/L N-butyryl-l-homoserine lactone (C4-HSL) after 6 h of culture and continued incubation to reach the time point of 72 h significantly promoted the secretion of EPSs, in which the content of extracellular proteins and extracellular polysaccharides was increased by 15.2% and 28.2%, respectively, compared with that of the control group. The biofilm electrodes induced by signaling molecules showed superior properties, which were evidenced by an increase of exceeding 20 μm in biofilm thickness, an increase of 33.9% in the proportion of living cells, enhanced electroactivity, and an increase of 10.7% in the uranium removal rate. The biofilm electrode was confirmed to immobilize uranium in wastewater mainly by electrosorption, physicochemical adsorption, and electro-reduction through characterization means such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This study provides a new technical idea for the efficient recovery of uranium in wastewater and enriches the theoretical system of quorum sensing regulation of electroactive biofilms.
Biofilms/drug effects* ; Acyl-Butyrolactones/pharmacology* ; Quorum Sensing/drug effects* ; Uranium/metabolism* ; Shewanella/metabolism* ; Adsorption ; Uranium Compounds/metabolism* ; Wastewater/chemistry* ; Biodegradation, Environmental ; Extracellular Polymeric Substance Matrix/metabolism*