This study aims to investigate the effects and mechanisms of the effective-compounds of Jinshui Huanxian formula (ECC-JHF) in improving pulmonary fibrosis. Animal experiments were approved by the Ethics Committee of the Animal Experiment Center of Henan University of Chinese Medicine (approval number: IACUC-202306012). The mouse model of pulmonary fibrosis was induced using bleomycin (BLM). Hematoxylin-eosin (H&E) staining was used to detect the histopathological changes of lung tissues. Masson staining was used to assess the degree of fibrosis in lung tissues. Immunofluorescence (IF) and real-time quantitative PCR (qPCR) were performed to measure the expression of collagen type I (COL I), α-smooth muscle actin (α-SMA), fibronectin (FN), interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) in lung tissues. Flow cytometry (FCM) was employed to detect the proportion of M1 and M2 macrophages in the bronchoalveolar lavage fluid (BALF) of mice. IF and qPCR were also used to detect the expression of lipase family member N (LIPN) in lung tissues. Free fatty acid assay kit was used to detect the level of free fatty acids in lung tissue. Bone marrow-derived macrophages (BMDMs) were treated with interleukin-4 (IL-4) to induce M2 polarization. FCM was used to measure the proportion of CD206⁺ M2 macrophages. IF was utilized to detect LIPN expression and lipid droplet decomposition. The results showed that in BLM-induced pulmonary fibrosis mice, ECC-JHF significantly attenuated BLM-induced alveolar inflammation and collagen deposition, inhibited fibroblast activation in lung tissues, and decreased the proportion of M2 macrophages in BALF. It also significantly suppressed LIPN expression and free fatty acid level in lung tissues. In the IL-4 induced BMDMs M2 polarization model, ECC-JHF significantly inhibited the proportion of CD206⁺ M2 macrophages, down-regulated the expression of LIPN, and blocked lipid droplet catabolism. These results suggest that ECC-JHF may alleviate bleomycin-induced pulmonary fibrosis by inhibiting lipid droplet decomposition and M2 macrophage polarization.

Objective: To investigate the association of serum alanine aminotransferase (ALT) with left ventricular hypertrophy (LVH) in adolescents, and to provide scientific evidence for the early screening and intervention strategy of cardiac structure damage. Methods: Data were obtained from the third follow up survey (October 2023) of the "Huantai Childhood Cardiovascular Health Cohort Study", including 1 156 healthy adolescents aged 12-17 with complete information. The sample population was stratified into low ( Q 1 group), medium ( Q 2 group), and high ( Q 3 group) ALT levels based on tertiles within the same gender and age groups. Inter group comparisons were conducted using analysis of variance and trend test. A multivariate Logistic regression model was used to analyze the association between ALT levels and LVH, and stratified analyses were performed by gender and age groups. Results: With the increase of ALT quantile level, the detection rate of LVH showed an increasing trend ( Q 1: 3.7%; Q 2: 10.6%; Q 3: 16.7%, Z= 5.89 , P <0.01). After adjusting for potential covariates, compared with the ALT group ( Q 1), the group ( Q 3) increased the risk of developing LVH in adolescents ( OR=2.09, 95%CI =1.21-4.12). Stratified analyses by age and sex showed a significant association only in boys and younger individuals aged 12 to 14 years [ OR (95% CI ) were 2.64(1.04-7.67) and 3.24( 1.35 -9.06), both P <0.05)]. Conclusion Elevated serum ALT levels are associated with an increased risk of LVH in adolescents, and early detection and control of abnormal liver enzyme levels can help reduce early vascular structural damage and prevent adverse cardiovascular events.

ObjectiveFat infiltration has been shown to be closely related to muscle mass loss and a variety of muscle diseases. This study proposes a method based on phase-angle electrical impedance tomography (ΦEIT) to visualize the electrical characteristic response caused by muscle fat infiltration, aiming to provide a new technical means for early non-invasive detection of muscle mass deterioration. MethodsThis study was divided into two parts. First, a laboratory pork model was constructed to simulate different degrees of fat infiltration by injecting1 ml or 2 ml of emulsified fat solution into different muscle compartments, and the phase angle images were reconstructed using ΦEIT. Second, a human experiment was conducted to recruit healthy subjects (n=8) from two age groups (20-25 years old and 26-30 years old). The fat content percentage η_fat of the left and right legs was measured by bioelectrical impedance analysis (BIA), and the phase angle images of the left and right calves were reconstructed using ΦEIT. The relationship between the global average phase angle Φ_M and the spatial average phase angle Φ_Mi of each muscle compartment and fat infiltration was further analyzed. ResultsIn the laboratory pork model, the grayscale value of the image increased with the increase of η_fat and Φ_M showed a downward trend. The results of human experiments showed that at the same fat content percentage, the Φ_M of the 26-30-year-old group was about 20%-35% lower than that of the 20-25-year-old group. The fat content percentage was significantly negatively correlated with Φ_M. In addition, the M₂ (soleus) compartment was most sensitive to fat infiltration, and the spatial average phase angles of the M₂ (soleus), M₃ (tibialis posterior and flexor digitorum longus), and M₄ (tibialis anterior, extensor digitorum longus, and peroneus longus) compartments all showed significant inter-group differences. ConclusionΦEIT imaging can effectively distinguish different degrees of fat infiltration, especially in deep, small or specially located muscles, showing high sensitivity, demonstrating the potential application of this method in local muscle mass monitoring and early non-invasive diagnosis.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

The pattern differentiation method is the most representative part of the inheritance of the experience of renowned practitioners of traditional Chinese medicine,reflecting their clinical thinking characteristics. Among them,Professor LYU Renhe proposed and developed the theory of abdominal masses in the long-term diagnosis and treatment of kidney diseases. Based on his clinical experience,he formed the method of differentiation of Shenluozhengjia (tangible or intangible abdominal masses of kidney collaterals). This differentiation method is characterized by its simple and easy clinical application. Tangible or intangible abdominal masses of kidney collaterals refer to chronic kidney disease,which is based on the basic cause of kidney deficiency. External or internal pathogenic factors cannot be eliminated,and prolonged illness invades the kidney collaterals,causing pathological products,such as qi stagnation,blood stasis,phlegm dampness,heat toxin,and turbid toxin to stagnate in the kidney collaterals,resulting in damage to the kidney body and loss of kidney function. The basic pathogenesis is a deficiency of kidney qi and the formation of tangible or intangible abdominal masses of the kidney collaterals. During pattern differentiation,the type is determined by the deficiency,which is fixed,and the pattern is determined by the excess,which is constantly changing with the condition and can be combined. Furthermore,he summarized the dietary principles as having more essence and less coarseness,more milk and less meat,a phased diet,and the selection of the symptomatic diet. To inherit and improve the theory and clinical practice of the pattern differentiation theory of tangible or intangible abdominal masses of kidney collaterals,this article reviews and summarizes the unique pattern differentiation method of the kidney collateral pattern from the aspects of definition,theoretical origin,etiology and pathogenesis,differentiation and treatment,and regulation,providing a basis for forming suitable diagnosis and treatment method for clinical promotion.

Objective: To investigate the clinical characteristics of induced labor in twin pregnancy and the related factors of induced labor failure. Methods: The clinical data of twin pregnant women who underwent induced labor in Peking University Third Hospital from January 2016 to December 2022 were retrospectively analyzed. According to whether they had labor or not after induction, pregnant women were divided into the success group (pregnant women who had labor after induction, 72 cases) and the failure group (pregnant women who did not have labor after induction, 30 cases). Logistic regression was used to analyze the related factors of induction failure in twin pregnant women. Results: The parity and cervical Bishop score in the failure group were significantly lower than those in the success group, while the proportion of dichorionic diamniotic twins, assisted reproductive technology pregnancy and cervical Bishop score <6, postpartum hospital stay and total hospital stay in the failure group were significantly higher than those in the success group (all P<0.05). The proportion of induced labor by artificial rupture of membranes ± oxytocin intravenous infusion in the success group was 72.2% (52/72), which was significantly higher than that in the failure group (46.7%, 14/30; P=0.030). There were no significant differences between the two groups in the gestational age at delivery, the incidence of severe postpartum hemorrhage and blood transfusion, the amount of postpartum hemorrhage, the neonatal weight of two fetuses, the incidence of neonatal asphyxia, and the proportion of neonates admitted to the neonatal intensive care unit (all P>0.05). There were no severe perineal laceration and hysterectomy in all pregnant women. Multivariate logistic regression analysis showed that primipara (OR=3.064, 95%CI: 1.112-8.443; P=0.030) and cervical Bishop score <6 (OR=5.208, 95%CI: 2.008-13.508; P=0.001) were the independent risk factors for induction failure in twin pregnancy. Conclusions: Elective induction of labor in twin pregnancy is safe and feasible. It is helpful to improve the success rate of induction of labor by strictly grasping the timing and indications of termination of pregnancy, choosing the appropriate method of induction according to the condition of the cervix, and actively promoting cervical ripening .
Infant, Newborn ; Pregnancy ; Female ; Humans ; Pregnancy Trimester, Third ; Pregnancy, Twin ; Postpartum Hemorrhage/etiology* ; Retrospective Studies ; Labor, Induced/methods* ; Cervical Ripening

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

Objective To investigate the regulatory role of ubiquitin-specific protease 10(USP10)on the protein expression of Krüppel-like factor 4(KLF4)and its impact on the proliferation and invasion ability of hepatocellular carcinoma(HCC)cells.Methods The protein expression differences of USP10 and KLF4 in normal liver cell line L02 and HCC cell lines,including HepG2,HUH7,HCCLM3 were detected by immunoblotting(Western blot)methods.HCCLM3 and HUH7 cells were selected,and lentiviral particles overexpressing or silencing USP10(oe-USP10 or sh-USP10)was transfected into the cells,and they were designated as the oe-USP10 group and oe-NC group,respectively.Immunoprecipitation(Co-IP)experiments were conducted to examine whether USP10 could di-rectly interact with KLF4 in HCCLM3 or HUH7 cells.The Co-IP assay was repeated in HCC cells transfected with oe-USP10 or sh-USP10,with the addition of the proteasome inhibitor MG132,which used to detect the ubiquitina-tion level of KLF4 protein in the transfected HCC cells.The pcDNA3.1 vector containing overexpressed KLF4 or its negative control plasmid(pc-KLF4 or pc-NC)was co-transfected into cells of the sh-USP10 group or sh-NC group.These cells were designated as the sh-NC+pc-NC group,sh-USP10+pc-NC group,sh-NC+pc-KLF4 group,and sh-USP10+pc-KLF4 group.The cell proliferation activity of each group was measured using the CCK-8 assay,and the cell invasion ability was assessed using the Transwell assay.Results Compared to L02 cells,the protein expres-sion of USP10 and KLF4 significantly decreased in HepG2,HUH7,HCCLM3,and other cells(P＜0.05).In HC-CLM3 and HUH7 cells,USP10 protein directly interacted with KLF4.Furthermore,treatment with MG132 resulted in a time-dependent increase in KLF4 protein expression in HCCLM3 and HUH7 cells.Silencing USP10 increased the ubiquitination of KLF4 in HCCLM3 or HUH7 cells,while overexpressing USP10 decreased the ubiquitination level of KLF4 in cells.Compared to the sh-NC+pc-NC group,both the proliferation activity and invasion ability of HCCLM3 and HUH7 cells significantly increased in the sh-USP10+pc-NC group(P＜0.01),while they signifi-cantly decreased in the sh-NC+pc-KLF4 group and sh-USP10+pc-KLF4 group(P＜0.05).Compared to the sh-USP10+pc-NC group,the proliferation activity and invasion ability of cells significantly decreased in the sh-USP10+pc-KLF4 group(P＜0.05).Conclusion USP10 can promote the stability of KLF4 protein through deubiquiti-nation in HCC cell lines,thereby inhibiting the proliferation and invasion of tumor cells.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.