AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

Objective To compare the value of 7 different thyroid imaging reporting and data systems(TI-RADS)for differentiating benign and malignant thyroid nodules under the context of Hashimoto thyroiditis(HT).Methods A total of 338 thyroid nodules in 200 HT patients were enrolled,including 167 benign and 171 malignant ones.Kwak-TIRADS,American Thyroid Association(ATA)guideline,American Association of Clinical Endocrinologists(A ACE)/American College of Endocrinology(ACE)/Associazione Medici Endocrinologi(AME)guideline,K-TIRADS of Korean Society of Thyroid Radiology,EU-TIRADS of European Thyroid Association,American College of Radiology(ACR)-TIRADS and 2020 Chinese guidelines for malignant risk stratification of thyroid nodules by ultrasound proposed by the superficial organs and vessels group of the ultrasound medicine branch of the Chinese Medical Association(C-TIRADS)were used for grading of benign and malignant thyroid nodules.Taken pathological results as gold standards,the diagnostic efficacy of 7 kinds of TI-RADS were analyzed.Results The sensitivity of Kwak-TIRADS,ATA guideline,A ACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS for differentiating benign and malignant thyroid nodules under the context of HT was 97.08％,98.25％,99.42％,95.91％,99.42％,90.06％and 99.42％,respectively,the specificity was 88.02％,83.23％,82.04％,88.02％,82.04％,86.83％and 84.43％,respectively,and the area under the curve(AUC)was 0.946,0.913,0.907,0.934,0.909,0.916 and 0.960,respectively.The sensitivity of C-TIRADS,EU-TIRADS and A ACE/ACE/AME guideline were all higher than that of K-TIRADS and ACR-TIRADS(all P＜0.05),and the specificity of Kawk-TIRADS and K-TIRADS were both higher than that of C-TIRADS,ATA guideline,EU-TIRADS and AACE/ACE/AME guideline(all P＜0.05),while AUC of C-TIRADS and Kawk-TIRADS were both higher than that of the rest 5 kinds of TI-RADS(all P＜0.05).According to Kwak-TIRADS,ATA guideline,AACE/ACE/AME guideline,K-TIRADS,EU-TIRADS,ACR-TIRADS and C-TIRADS,the malignant rate of different grades nodules identified with the same TI-RADS were significant different(all P＜0.05),which all raised with the increase of TI-RADS grade.Conclusion C-TIRADS and Kawk-TIRADS had better value for differentiating benign and malignant thyroid nodules under the context of HT,among which C-TIRADS had higher sensitivity and Kawk-TIRADS had higher specificity.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China. Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5. Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV. Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*