ObjectiveTo investigate the trends in the disease burden of falls among Chinese children and adolescents from 1990 to 2021, and to inform the development of targeted prevention and control strategies. MethodsData on age-standardized incidence rate, age-standardized mortality rate and age-standardized disability-adjusted life years (DALYs) rate for falls among Chinese children and adolescents under 20 years of age from 1990 to 2021 were systematically extracted from the Global Burden of Disease Study (GBD) 2021 database. The annual percent change (APC) and average annual percent change (AAPC) were calculated to evaluate temporal trends in fall-related disease burden across different age groups and sexes. ResultsFrom 1990 to 2021, the age-standardized incidence rate of falls among Chinese children and adolescents showed a non-linear fluctuation (AAPC=0.08%, P=0.040), while both the age-standardized mortality rate and age-standardized DALYs rate declined (AAPC=-3.66% and -3.09%, both P<0.001). The crude incidence rate decreased in the <5 years old and 5 ‒ <10 years old groups (AAPC=-1.38% and -0.29%, both P<0.001), but increased annually in the 10 ‒ <15 years old and 15 ‒ <20 years old groups (AAPC=0.27% and 0.81%, both P<0.001). The crude mortality rate and crude DALYs rate declined across all four age groups, with the most significant reduction observed in the <5 years old group (AAPC=-5.21%, 95%CI:-5.55%‒ -5.00%; AAPC=-4.98%, 95%CI: -5.20%‒ -4.79%, both P<0.001). For both males and females, the age-standardized incidence rate of falls showed a V-shaped trend (initial decline followed by a subsequent rise). In contrast, the age-standardized mortality rate and age-standardized DALY rate declined in both sexes, with an AAPC of -3.40% and -2.94% for males, and -4.50% and -3.49% for females, respectively (all P<0.001). ConclusionThe overall disease burden of falls among Chinese children and adolescents has been substantially improved; however, the incidence burden remains considerable. Future prevention efforts should be tailored to age- and sex-specific characteristics, with the family as the fundamental care unit in conjunction with high-quality nursing extension services, to establish a closed-loop management model encompassing “early identification, immediate intervention, and continuous follow-up.”

ObjectiveTo investigate the effects of Yifei Zhuji formula （YFZJF） on epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） through regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsThe Lewis lung carcinoma mouse model and human lung adenocarcinoma PC-9 cell model were used in this study. In the animal experiments， 60 C57BL/6 mice were randomized into a blank group and a Lewis lung carcinoma modeling group. The modeled mice were further randomized into model， low-， medium-， and high-dose （7.475， 14.95， 29.9 g·kg^-1·d^-1， respectively） YFZJF， and cisplatin groups， with 10 mice in each group. Mice in YFZJF groups were administrated with YFZJF at different doses by gavage， and those in the cisplatin group received intraperitoneal injection of cisplatin at 6 mg·kg^-1. Mice in the blank group and model group were administrated with equal volumes of normal saline by gavage every day. All the groups were treated for 14 consecutive days， and samples were collected for analysis after completion of treatment. Changes in body mass， tumor volume， and tumor mass were measured. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the lung tissue. Immunohistochemistry， Real-time PCR， and Western blot were employed to determine the expression of proliferating cell nuclear antigen （Ki-67）， PI3K/Akt/mTOR signaling pathway-related molecules， and EMT-related molecules in the tumor tissue. In the cell experiments， human lung adenocarcinoma PC-9 cells were allocated into control， YFZJF-containing serum， and cisplatin groups， which were treated with 20% blank rat serum， 20% YFZJF-containing rat serum， and 5.4 μmol·L^-1 cisplatin for 48 h， respectively. The cell counting kit-8 （CCK-8） assay was adopted to detect cell proliferation and determine drug concentration. Cell scratch assay and Transwell assay were employed to evaluate cell migration and invasion. Immunofluorescence staining and Real-time PCR were used to analyze changes in expression of EMT markers. ResultsCompared with those in the model group， the tumor volume and tumor mass were reduced in the high-dose YFZJF group （P<0.01）. Immunohistochemical results showed that compared with the model group， the medium- and high-dose YFZJF groups exhibited reduced Ki-67 expression in the tumor tissue （P<0.01）. HE staining results showed that YFZJF alleviated the pathological injury of the lung tissue to different degrees. Real-time PCR results in the tumor tissue showed that compared with the model group， the high-dose YFZJF group displayed downregulated mRNA levels of protein kinase B1 （Akt1） and N-cadherin （P<0.05）， phosphatidylinositol 3-kinase p85 regulatory subunit （p85） （P<0.01）， mTOR （P<0.01）， and Vimentin （P<0.01）， and an upregulated mRNA level of E-cadherin （P<0.01）. Western blot results showed that compared with the model group， the high-dose YFZJF group exhibited downregulated protein levels of phosphorylated （p）-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， Vimentin， and N-cadherin （P<0.01）， and an upregulated protein level of E-cadherin （P<0.01） in the tumor tissue. The cell experiment results showed that compared with the blank serum group， YFZJF-containing serum inhibited the proliferation， migration， and invasion of PC-9 cells （P<0.05， P<0.01）. Immunofluorescence results showed that compared with the control group， YFZJF-containing serum downregulated the protein levels of N-cadherin and Vimentin and upregulated the protein level of E-cadherin （P<0.01）. Real-time PCR results showed that compared with the control group， YFZJF-containing serum upregulated the mRNA level of E-cadherin （P<0.05） and downregulated the mRNA levels of N-cadherin， Vimentin， P85， Akt1， and mTOR （P<0.05， P<0.01）. ConclusionYFZJF can significantly inhibit the progression of non-small cell lung cancer and reduce the migration and invasion of tumor cells by inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway and reversing EMT.

OBJECTIVES: To analyze the differential expression and biological functions of circRNAs in the anterior lens capsules of high myopic patients with cataract and their pathogenic roles in the development of this condition. METHODS: Anterior lens capsule specimens were collected intraoperatively from 36 patients with age-related cataract (ARC) and 36 high myopic patients with cataract. Among these, 18 specimens from each group were selected for whole transcriptome sequencing and biological analysis, and the remaining 36 specimens were used for validation of circPDGFRA, circFOXJ3, hsa_circ_0004767, hsa_circ_0007528, ciCRIM1, circMAN1A2, circSLC5A3, and circPTK2 expressions using RT-qPCR. hsa_circ_0007528 was selected for cell experiments to examine its effects on proliferation, migration, and apoptosis of lens epithelial cells (LECs). RESULTS: A total of 16 192 circRNAs were detected in the specimens from both groups, among which 62 circRNAs were differentially expressed (29 upregulated and 33 downregulated). GO and KEGG analyses revealed that the differentially expressed circRNAs were primarily localized in the cytoplasm, nucleoplasm, and endoplasmic reticulum, and were involved in signaling pathways associated with Gap junction and the PI3K-Akt, NF-κB, Jak-STAT, HIF-1, and MAPK signaling pathways. The ceRNA network predicted multiple target genes. RT-qPCR validation results were consistent with the sequencing data. In the LECs, upregulation of hsa_circ_0007528 significantly inhibited cell proliferation and migration and obviously promoted cell apoptosis. CONCLUSIONS The expression profile of circRNAs in the anterior lens capsule of high myopic patients with cataract differs from that of ARC patients. Upregulation of hsa_circ_0007528 inhibits LEC proliferation and migration and promotes cell apoptosis.
Humans ; Cataract/complications* ; RNA, Circular ; Myopia/genetics* ; Apoptosis ; Cell Proliferation ; Epithelial Cells ; Cell Movement ; Anterior Capsule of the Lens/metabolism* ; Male ; Female

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Image 1.

OBJECTIVE: To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury. METHODS: A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups. RESULTS: A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05]. CONCLUSIONS Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans ; Retrospective Studies ; Liver/physiopathology* ; Risk Assessment ; APACHE ; Wounds and Injuries ; Adult ; Injury Severity Score ; Male ; Middle Aged ; Female ; Liver Function Tests ; Alanine Transaminase/blood* ; Young Adult ; Aspartate Aminotransferases/blood*

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy