A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To analyze the clinical efficacy of three-dimensional(3D) reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy for the pulmonary nodules.Methods:We retrospectively analyzed 50 patients with nodules who underwent uniportal fluorescence thoracoscopic subsegmentectomy from December 2021 to February 2024. All patients underwent thin-slice CT scanning and 3D reconstruction preoperatively. 12 patients were given CT-guided hookwire localization preoperatively.The intersegmental plane was identified by fluorescence method.Results:One patient was converted to right upper lobectomy due to no lesion found in S1b. The mean blood loss was(23.4±16.5)ml and the mean operative time was(126.5±38.5)min. The mean duration of postoperative drainage was(2.6±0.8)days. Mean postoperative hospitalization was(4.8±1.8)days. There were 2 cases with postoperative pulmonary infections, including one with encapsulated pleural effusion. There was no air leakage over 3 days, and no death within 30 days after surgery.Conclusion:3D reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy is a safe and feasible technique for resection of pulmonary nodules in lung subsegments, and surgical indications must be strictly controlled.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To compare regional pulmonary ventilation and perfusion and ventilation/perfusion(V/Q)matching in different body positions using electrical impedance tomography(EIT).Methods Ten healthy experimental pigs were selected to collect their EIT lung ventilation and perfusion data in supine,prone,left lateral and right lateral positions.The EIT data underwent analysis and image reconstruction using MATLAB R2022b and EIDORS v3.9.The effective regions with ventilation and perfusion were determined and the V/Q matching regions were computed with the maximum pixel value 20％as the threshold.Comparisons were carried out over the V/Q matching indexes including V/Q match％,dead space％and shunt％and ventilation and perfusion distribution in regions of interest(ROIs)including ROI1,ROI2,ROI3 and ROI4 in different body positions.Results The differences in V/Q match％,dead space％and shunt％of the experimental animals in varied positions were not statistically significant(P＞0.05).The regional distribution of pulmonary ventilation and perfusion changed in different positions,and the regional distributions differed in ROIl,ROI2 and ROI3 for ventilation(P＜0.05)and in ROI1 and ROI2 for perfusion(P＜0.05).The ventilation and perfusion regions were distributed consistently with the gravity-dependent areas in supine and prone positions whereas conversely in the right and left lateral positions.Conclusion The V/Q matching indexes of one subject have high test consistency in different body positions;gravity-dependent areas varied with the changes of the body positions,which affected the distribution of pulmonary ventilation and perfusion regions;EIT can be used for measuring the changed pulmonary ventilation and perfusion due to different positions and determining the influences of position changes on pulmonary ventilation and perfusion and V/Q matching.[Chinese Medical Equipment Journal,2024,45(5):1-7]

Objective    To summarize the clinical experience of thoracoscopic combined subsegmentectomy (CSS). Methods    The clinical data of 76 patients who underwent thoracoscopic CSS in Anqing Municipal Hospital from May 2018 to July 2022 were retrospectively analyzed, including 22 males and 54 females, aged 27.0-76.0 (54.3±10.5) years. All patients underwent preoperative three-dimensional computed tomography bronchography and angiography using dual source CT. The modified inflation-deflation technique or indocyanine green was used to identify the intersubsegmental border. Results    A total of 86 pulmonary nodules were resected in 76 patients. One patient of left upper lobe S1+2c+S4a, 1 patient of right upper lobe S2b+S3a and 1 patient of right upper lobe S1b+S3b were further performed lobectomy due to insufficient margin. One patient of left upper lobe S1+2+S3a was further performed left upper division segmentectomy due to residual atelectasis. One patient of left upper lobe S1+2c+S3a was further performed left upper division segmentectomy due to B3b+c injury, and the rest completed planned surgeries successfully. The operative time was 90.0-350.0 (174.9±53.2) min. The operative hemorrhage volume was 50.0 (20.0, 50.0) mL. The postoperative hospital stay time was 6.0 (5.0, 7.0) d. Postoperative complications included pulmonary infection in 9 patients, hemoptysis in 3 patients, persistent pulmonary leakage>3 d in 4 patients, pneumothorax in 1 patient, pleural effusion in 1 patient, and myocardial infarction in 1 patient. All of the patients were cured and discharged without perioperative death. Conclusion    Thoracoscopic CSS is relatively complex. Preoperative planning under three-dimensional reconstruction and intraoperative fine operation are helpful for safe completion.

OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with GradeⅡKOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m^-2 with an average of (23.80±2.86) kg·m^-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m^-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m^-2 with an average of(23.42±2.97) kg·m^-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m^-2 with an average of (24.15±2.33) kg·m^-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m^-2 with an average of (23.79±2.49) kg·m^-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.
Aged ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Medicine, Chinese Traditional ; Osteoarthritis, Knee ; Syndrome ; Wind ; Cold Temperature