Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective:To investigate the association between small vulnerable newborn (SVN) phenotypes and the risk of neurodevelopmental delay at the age of 1 year.Methods:A prospective cohort study was conducted. A total of 25 860 singleton infants from "The Born in Guangzhou Cohort Study" who completed the Gesell developmental scale assessment at 1 year of age between January 2013 and June 2025 were included. Maternal sociodemographic characteristics, and other information were collected using a self-administered questionnaire, and maternal pregnancy-related information and neonatal birth data were extracted from medical records. Global developmental delay (GDD) was defined as a developmental quotient below 86 in ≥3 domains of the Gesell developmental scale, which assesses the adaptive, gross motor, fine motor, language, and personal-social domains. The random forest algorithm was employed for missing data imputation. Based on prematurity, small for gestational age (SGA), and low birth weight (LBW), newborns were categorized into 6 phenotypes: preterm-SGA-LBW, preterm-appropriate for gestational age (AGA)-LBW, preterm-AGA-nonLBW, term-SGA-LBW, term-LBW-only or term-SGA-only, and term-AGA-nonLBW phenotype. Among these, the first 5 were classified as SVN phenotypes, and the last one served as the reference group. Inter-group comparisons were performed using analysis of variance (ANOVA), χ2 tests, or Kruskal-Wallis test, as appropriate.?? Multivariable robust Poisson regression models were applied to analyze the association of different SVN phenotypes with the risks of GDD and developmental delays in specific domains, with stratified analyses by sex. Results:Among the 25 860 infants, 13 719 (53.1%) were male and 12 141 (46.9%) were female. The gestational age at birth was 39.4 (38.6, 40.0) weeks. The overall detection rate of GDD at 1 year of age was 3.7% (962/25 860). The rates of delay across developmental domains, in descending order, language in 8 134 cases (31.5%), gross motor in 4 488 cases (17.4%), personal-social in 1 271 cases (4.9%), adaptive in 1 262 cases (4.9%), and fine motor in 621 cases (2.4%). Compared with the reference group, preterm-AGA-LBW, preterm-SGA-LBW, preterm-AGA-noneLBW, and term-SGA-LBW phenotypes were all associated with an increased risk of GDD, with the adjusted RR (95% CI) of 6.07(5.01-7.35), 4.81(3.11-7.46), 2.10(1.54-2.88) and 1.89(1.29-2.76) respectively.The preterm-AGA-noneLBW phenotype was all associated with an increased risk of delay in gross motor, language and personal-social functional domains (all P<0.05). The term-SGA-LBW phenotype was associated with an increased risk of delay in gross motor, fine motor and personal-social functional domains (all P<0.01). Whereas the term-LBW-only or term-SGA-only phenotype showed no statistically association with developmental delay in any functional domain (all P≥0.05). Conclusion:The combined classification based on gestational age and birth weight helps identify infants at high risk for neurodevelopmental delay at 1 year of age, suggesting that it may offer a reference for the rational allocation of clinical resources.

Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective:To analyze the clinical and ultrasonic features of breast invasive ductal carcinoma in young women patients,and improve the accuracy of ultrasonic diagnosis of breast invasive ductal carcinoma in young patients.Methods:A retrospective study was conducted on patients with invasive ductal carcinoma who underwent surgery in the Second Hospital of Shandong University from December 2015 to June 2023,with complete clinical data,preopera-tive ultrasonography and postoperative pathology.All patients were divided into two groups:young group(≤35 year-old)and control group(>35 year-old).Univariate t-test and multivariate Logistic regression analyses were used to assess the factors.Results:There was a statistical difference between the young group and the control group in the accuracy of ultrasound diagnosis(young group 81%vs control group 94%,χ2=13.082,P=0.001).Compared with the control group,the young group had a shorter disease history,a higher proportion of multiple masses,posterior echo changes and hypo-vascular lesions(P<0.05).However,there was no statistical difference in family history of breast cancer,other cancer family history,clinical symptoms,size,lesion classification,palpation,location,aspect ratio,focus echo,shape,edge per-formance,bright ring sign,calcification characteristics,ER,PR,HER-2 and Ki67(P>0.05).Conclusion:The incidence rate of young breast IDC is low,while the misdiagnosis rate of ultrasound is relatively high.More attention should be paid when the patient has a short history,multiple masses,changes in the posterior echo and less lesion blood supply.

Objective To explore the clinical effect of totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunos-tomy for gastric cancer.Methods Ninety cases of gastric cancer patients were seleted,of which 45 cases undergoing Roux-en-Y esophagoje-junostomy for digestive tract reconstruction were set as the control group,while 45 cases undergoing hand-sewn esophagojejunostomy for digestive tract reconstruction were set as the observation group.Patients in the control group underwent laparoscopic-assisted total gastrectomy combined with Roux-en-Y esophagojejunostomy to reconstruct digestive tract,while patients in the observation group underwent totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunostomy to reconstruct digestive tract.The perioperative indicators and complications of patients in the two groups were compared.Results The surgical time,time of esophagojejunostomy,and time to get out of bed after surgery of patients in the observation group were significantly shorter than those in the control group(P<0.05),the pain score 24 hours after surgery was significantly lower than that in the control group(P<0.05).There was no statistically significant difference between the two groups in terms of the incidence of complications or Clavien-Dindo grading(P>0.05).Conclusion Hand-sewn esophagojejunostomy for digestive tract reconstruction has a good clinical effect in gastric cancer during totally laparoscopic total gastrectomy.It can shorten the surgical time and time of esophagojejunostomy,reduce postoperative pain,and accelerate postoperative recovery,whose safety is comparable to Roux-en-Y esophagojejunostomy.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective:To explore the trajectory of depressive symptoms and its related factors in rural women in Yunnan from first trimester of pregnancy to 42 days after childbirth.Methods:The longitudinal study design was used,and 213 pregnant women from a rural county of Yunnan were selected.The Edinburgh Postnatal Depression Scale(EPDS),Generalized Anxiety Disorder(GAD-7),and Perceived Social Support Scale(PSSS)were used to surveyed in their first trimester of pregnancy,and followed up in their second and third trimesters of pregnancy and 42 days after childbirth.The analysis was conducted using latent growth curve models,latent class growth models,and multivariate logistic regression models.Results:The results of the latent growth curve models showed a gradual decrease in perinatal depressive symptom scores over time.The latent class growth models revealed three distinct la-tent classes:persistent high depression score group(1.41％),stable low depression score group(91.08％),and fluctuating depression symptoms group(7.51％).Multivariate logistic regression indicated that women with lower education levels(OR=4.04),anxiety symptoms(OR=4.12),and lower social support(OR=3.12)were more likely to be classified into the persistent high depression score group and fluctuating depression symptoms group.Conclusions:The trajectories of perinatal depression symptoms among rural women in Yunnan could be di-vided into three heterogeneous subgroups.Women with low education levels,anxiety symptoms,and lack of social support are more likely to be detected with perinatal depression symptoms.

Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.