Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

ObjectiveTo investigate the effects of different doses of uncooked corn starch （UCCS）， type 2 resistant starch， on intestinal mucosal barrier function in mice and to explore the potentional underlying mechanisms. MethodsTwenty C57BL/6 mice were randomly assigned to four groups and fed either a standard diet （control group） or diets supplemented with low （188.8 g/kg）， medium （314.8 g/kg）， or high （440.6 g/kg） doses of UCCS for 8 weeks. Body weight and disease activity index （DAI） were monitored. At the endpoint， colon length was measured； histopathological changes in were assessed via HE staining. The expression of tight junction proteins （ZO-1， E-cadherin， and Villin） in the colonic mucosa were detected using immunofluorescence. Serum inflammatory cytokines （IL-6， TNF-α， IL-1β， MIP-1α/CCL3） and fecal calprotectin levels were measured by ELISA. Gut microbiota alterations were analyzed via 16S rRNA gene sequencing and PICRUSt2 functional prediction. ResultsCompared with the control group， UCCS intervention across all doses significantly shortened colon length （P=0.000 5） and increased colonic inflammation scores （P=0.013 3）. Immunofluorescence revealed a significantly reduction in the expression and co-localization of ZO-1 and Villin in the colonic mucosa （P＜0.05）. Systemic inflammation was evidenced by significantly elevated serum levels of IL-6 （P=0.006 4）， TNF-α （P=0.000 1）， IL-1β （P=0.001 4）， and MIP-1α/CCL3 （P＜0.000 1）. Fecal calprotectin levels were also significantly increased during the early phase （weeks 1-2， P＜0.05）. 16S rRNA sequencing showed that UCCS significantly altered the β-diversity of the gut microbiota （P＜0.05）， characterized by the enrichment of butyrate-producing Clostridia_UCG-014， and the opportunistic pathogen Desulfovibrio， alongside a decreased abundance of immunomodulatory genera Akkermansia and Dubosiella. PICRUSt2 analysis suggested that UCCS modulated metabolic pathways related to energy metabolism， glutathione metabolism， and sulfur cycling. ConclusionLong-term or high-dose intake of UCCS may disrupt gut microbiota homeostasis and trigger inflammation response， thereby damaging the intestinal mucosal barrier. These findings suggest that the clinical or dietary application of UCCS should be cautioned regarding dose-dependent risks of intestinal injury.

Objective To observe brain structural changes in preterm infants and to analyze associated clinical risk factors based on 3D T1 structural MRI.Methods Brain 3D T1 structural MRI data of 82 preterm infants(preterm group)and 50 term infants(term group)were analyzed.Cortical morphology,including cortical thickness,surface area,sulcal depth and gyrification index were compared between groups.Spearman partial correlation analysis was used to explore the correlations of cortical structural changes and perinatal clinical variables.Results Compared with those in term group,increased cortical thickness of the right caudal middle frontal gyrus,reduced surface area of the left inferior parietal lobule,left precuneus and bilateral supramarginal gyrus,as well as decreased gyrification index in the right superior temporal gyrus,right lateral occipital gyrus,left inferior parietal lobule and left parahippocampal gyrus were observed in preterm group(all FDR corrected P＜0.05).No significant difference of sulcal depth was found between groups(all P＞0.05).Cortical surface area in bilateral supramarginal gyrus of preterm infant lowly-weakly negatively(rs=-0.327,-0.267,both P＜0.05)correlated,while the gyrification index in left parahippocampal gyrus of preterm infant weakly and positively(rs=0.221,P=0.045)correlated with maternal gestational diabetes mellitus.The surface area of left inferior parietal lobule,left precuneus,left supramarginal gyrus and right supramarginal gyrus in preterm infant weakly and negatively correlated with maternal infection during pregnancy(rs=-0.284—-0.224,all P＜0.05).Meanwhile,cortical thickness of the right caudal middle frontal gyrus and surface area of the right supramarginal gyrus in preterm infant lowly and negatively correlated with premature rupture of membranes(rs=-0.311,-0.301,both P＜0.05).Conclusion 3D T1 structural MRI was useful for detecting abnormal cortical morphology of preterm infants.Maternal gestational diabetes,infection during pregnancy and premature rupture of membranes might be risk factors for abnormal brain structure in newborns.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Objective:To analyze the effects of parenting care map of premature infants on parenting competence and parenting stress of primipara, with a view to providing a theoretical basis for the development, implementation and modification of clinical interventions.Methods:Convenient sampling method was used to select primigravid women who gave birth in Lishui Maternal and Child Health Hospital from January 2023 to January 2024 for randomized controlled study, which was divided into the observation group and the control group according to the random number table. The control group received routine nursing, and the observation group guided the parents of premature infants to draw the child care map together on the basis of the control group. The scores of Chinese version of parenting sense of competence scale ( C-PSOC ) and Chinese version of Simplified Parenting Stress Index ( PSI-SF ) before and after intervention were compared.Results:A total of 120 cases of primiparous women who met the inclusion and exclusion criteria were enrolled, 60 cases in the control group and 60 cases in the observation group. The age of the control group was (26.25 ± 3.93) years, and the age of the observation group was (25.86 ± 4.22) years. Before the intervention, the difference between the C-PSOC dimension scores and total scores, PSI-SF dimension scores and total scores of the 2 groups was not statistically significant (all P>0.05). After the intervention, the maternal C-PSOC efficacy, satisfaction dimension scores and total scores of primiparous women in the observation group were (32.05 ± 6.27), (40.29 ± 8.19), and (72.23 ± 9.39) points, respectively, which were higher than those of the control group, which were (28.46 ± 6.47), (37.08 ± 8.06), and (65.53 ± 10.24) points, and the differences between the 2 groups were all statistically significant ( t = 3.09, 2.16, 3.74, all P<0.05). After the intervention, the PSI-SF scores and total scores of primiparous women in the observation group on the dimensions of parental distress, personal interaction disorder, and difficult child were (24.43 ± 5.44), (27.51 ± 6.53), (29.47 ± 5.82), and (81.54 ± 10.38) points, respectively, which were lower than those of the control group (28.57 ± 5.52), (30.19 ± 7.02), (32.78 ± 5.37), and (90.97 ± 10.12) points, and the differences between the 2 groups were all statistically significant ( t = 4.41, 2.17, 3.23, 5.04, all P<0.05). Conclusions:Premature child care map can effectively improve the parenting sense of competence of primiparas and reduce their parenting pressure. It is a convenient and effective nursing intervention tool.

Various researches have reported on the relationship between homocysteine levels and adverse pregnancy outcomes. Researchers are increasingly focusing on the impact of homocysteine on female reproductive health and figuring out the potential positive effects of lowering homocysteine levels on women fertility. Our review aims to systematically summarize the possible roles of homocysteine in female reproductive disorders based on relevant studies from the past 15 years and therapeutic prospects targeting homocysteine to improve the reproductive health of women.

Purpose To explore the feasibility and validity of radiomics combined with blind/referenceless image spatial quality evaluator(Brisque)for automated assessment of arterial-phase image quality in hepatic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)dynamic enhanced MRI examinations.Materials and Methods A total of 326 arterial phase images from January 2020 to March 2024 in the First Affiliated Hospital of Henan University of Chinese Medicine for liver Gd-EOB-DTPA dynamic enhancement MRI examination were retrospectively collected.A 4-level(1-4 points)Likert scale was used for subjective image quality scoring,and then binary classification was used to divide the images into clinically acceptable group(166 images with a score of 2-4)and clinically unacceptable group(160 images with a score of 1).All images were randomly divided into a training set(227 images)and a test set(99 images)in a 7∶3 ratio.Brisque images were created based on arterial-phase images,and subsequently Brisque image features,image histologic features of the original arterial-phase images and combined features of the two were extracted.The extracted data were reduced in dimension and the optimal features of radiomics were selected.Based on the Logistic regression algorithm,radiomics models,Brisque models and combined models of the two were constructed.The receiver operating characteristic curve was drawn for each subject,and the area under the curve(AUC),threshold,sensitivity,specificity,accuracy,negative predictive value and positive predictive value were calculated to analyze the diagnostic performance of each model,and the net benefit of the models was evaluated by decision curve analysis.Results The AUC values of the radiomics model,Brisque model and combined model in the training set were 0.942(95%CI 0.914-0.969),0.722(95%CI 0.655-0.788)and 0.967(95%CI 0.947-0.987),respectively.In the test set,the AUC values were 0.904(95%CI 0.848-0.960),0.684(95%CI 0.579-0.789)and 0.920(95%CI 0.866-0.972),respectively.There was statistically significant difference between two of the three models in the training set(Z=6.493,3.397,7.427;all P<0.05);in the test set,there was statistically significant difference between the combined model and the Brisque model,and between the radiomics model and the Brisque model(Z=4.137,3.740,both P<0.05),but no statistically significant difference between the combined model and the radiomics model(P>0.05).The diagnostic performance was higher in the combined model in both the training set and the test set.The decision curve analysis curve suggested that the net benefit of the combined model was greater than that of the other two models.Conclusion Radiomics combined with Brisque can be applied in the assessment of the quality of arterial-phase images in Gd-EOB-DTPA dynamic-enhanced MRI examinations of the liver to automatically detect clinically unacceptable arterial-phase images of the liver with high diagnostic efficacy,which contributes to the improvement of the quality of the images at the time of acquisition,leading to a reduction in the number of duplicate scans and an increase in the accuracy of the diagnosis.