BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Fibroblasts are stromal cells widely distributed in tissues and organs throughout the body.Fibroblasts are involved in the synthesis and remodelling of the extracellular matrix.Fibroblasts participate in physiopathological processes such as tissue damage repair,inflammatory responses and immune regulation.Large numbers of activated fibroblasts have been found in fibrosis,autoimmune diseases and tumor lesions.Activated fibroblasts participate in tissue fibrosis and influence the tumor microenvi-ronment mainly by secreting collagen and fibronectin.They also secrete a variety of inflammatory and growth factors that play an immunomodulatory role in autoimmunity and tumors.In recent years,it has been found that modulating fibroblast activation can effectively delay the development of these diseases,and that targeting fibroblast activation biomarkers can assess the development and treatment of these diseases.Therefore,the use of fibroblast-targeted drugs and therapeutic tools is expected to achieve new breakthroughs in the clinical management of fibrosis,autoimmune diseases and tumors.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

OBJECTIVE: To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis. METHODS: Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism. RESULTS: Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota. CONCLUSIONS Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.
Rats ; Male ; Animals ; Tumor Necrosis Factor-alpha ; RNA, Ribosomal, 16S ; Gastrointestinal Microbiome ; Interleukin-6 ; Rats, Wistar ; Sepsis

Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.

There are eight forms of vitamin E in human blood, including α-, β-, γ-, δ-tocopherols and α-, β-, γ-, δ-tocotrienols. As the most abundant and active form of vitamin E, α-tocopherol is widely accepted as a reliable indicator for nutritional assessment of body vitamin E status across the world. Considering that different vitamin E forms have diverse biological activities, separation and detection of different vitamin E forms in human blood facilitates the understanding of the association between vitamin E and diseases. In this review, the advances in sample-pretreatment techniques and detection techniques for vitamin E in human blood were presented. Currently, the sample-pretreatment techniques include solid-phase extraction, liquid-liquid extraction, dispersive liquid-phase microextraction, supported liquid extraction and direct protein precipitation; the detection techniques include automatic biochemical analysis, enzyme-linked immunosorbent assay, gas chromatography, liquid chromatography and ultra-high performance supercritical fluid chromatography mass spectrometry. This review summarizes the characteristics and scope of above-mentioned techniques used for detection of vitamin E in human blood, so as to provide insights into the selection of an appropriate method for inspection technicians.

Objective:To explore the biological behavior of small tumor (≤1.0 cm) breast cancer with axillary lymph node metastasis as the first symptom, and to provide a powerful reference for clinical accurate treatment.Methods:The clinical, pathological and follow-up data of 60 breast cancer patients with small tumor and axillary lymph node metastasis as the first symptom admitted to the Second Affiliated Hospital of Harbin Medical University and the Third Affiliated Hospital of Harbin Medical University from 2017 to 2019 were analyzed retrospectively (study group). Meanwhile, non-small tumor with negative lymph node (control group A), non-small tumor with positive lymph node (control group B) and small tumor with negative lymph node (control group C) were included as control groups. Selected estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor-2(Her-2) and Ki67 to compare and analyze the difference between primary lesions and axillary lymph node metastasis, and made a comprehensive analysis with the follow-up data.Results:There were no statistically significant differences in the four indexes in primary lymph nodes and metastatic lymph nodes between the study group and the control group ( P>0.05). The expression of HER-2 in control group B, study group, control group C, control group A showed a decreasing trend. In the study group, there were 19 cases with >3 axillary lymph node metastasis, the positive rate of HER-2 was 11/19, and 37 cases with 3 lymph node metastasis, the positive rate of HER-2 was 21.6%(8/37), the difference was statistically significant ( P<0.05), but there was no significant difference in the expression of ER, PR and Ki67 ( P>0.05). In control group B, there was no significant difference between the groups with >3 axillary lymph node metastasis and 3 groups ( P>0.05). Combined with the follow-up data, in the study group with >3 lymph node metastasis, there were 4 cases with distant metastasis and Ki67 expression rate was 4/4, while there were 13 cases with no distant metastasis and Ki67 expression rate was 5/13, the difference was statistically significant ( P<0.05). Conclusions:The expressions of ER, PR, Her-2 and Ki67 in primary breast cancer including small tumor and axillary lymph node metastasis are consistent. In most cases, the overall condition can be evaluated by biological indicators of primary disease, but some patients do have inconsistencies, which should arouse the attention of clinicians for comprehensive condition evaluation. Her-2 positive expression seems to be related to axillary lymph node metastasis as a whole, especially in small tumor breast cancer with T≤1.0 cm. For patients with axillary lymph node metastasis and invasive ductal carcinoma with primary lesion ≤1.0 cm, the high expression of Ki67 seems to indicate that distant metastasis is more likely to occur in the longer term.

Background Occupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases in the world. With the development of industry, noise sources in the workplace have become increasingly complex. Objective To apply kurtosis-adjusted cumulative noise exposure (CNE) to assess the occupational hearing loss among furniture manufacturing workers, and to provide a basis for revising noise measurement methods and occupational exposure limits in China. Methods A cross-sectional survey was conducted to select 694 manufacturing workers, including 542 furniture manufacturing workers exposed to non-Gaussian noise, and 152 textile manufacturing workers and paper manufacturing workers exposed to Gaussian noise. The job titles involving non-Gaussian noise were gunning and nailing, and woodworking, while those involving Gaussian noise were weaving, spinning, and pulping. High frequency noise-induced hearing loss (HFNIHL) and noise exposure data were collected for each study subject. Noise energy metrics included eight-hour equivalent continuous A-weighted sound pressure level (L_{Aeq,8 h}) and CNE. Kurtosis was a noise temporal structure metric. Kurtosis-adjusted CNE was a combined indicator of noise energy and temporal structure. Results The age of the study subjects was (35.64±10.35) years, the exposure duration was (6.71±6.44) years, and the proportion of males was 75.50%. The L_{Aeq,8 h} was (89.43±6.01) dB(A). About 81.42% of the study subjects were exposed to noise levels above 85 dB(A), the CNE was (95.85±7.32) dB(A)·year, with a kurtosis of 99.34 ± 139.19, and the prevalence rate of HFNIHL was 35.59%. The mean kurtosis of the non-Gaussian noise group was higher than that of the Gaussian noise group (125.33±147.17 vs. 5.86±1.94, t=−21.04, P<0.05). The results of binary logistic regression analysis showed that kurtosis was an influential factor of workers' HFNIHL after correcting for age, exposure duration, and L_{Aeq,8 h} (OR=1.49, P<0.05). The results of multiple linear regression analysis showed that the effects of age, exposure duration, L_{Aeq,8 h}, and kurtosis on noise-induced permanent threshold shift at frequencies of 3, 4, and 6 kHz of the poor hearing ear were statistically significant (all P<0.05). The results of chi-square trend analysis showed that when CNE ≥ 90 dB(A)·year, the HFNIHL prevalence rate elevated with increasing kurtosis (P<0.05). The mean HFNIHL prevalence rate was higher in the non-Gaussian noise group than in the Gaussian noise group (31.7% vs. 22.0%, P<0.05). After applying kurtosis-adjusted CNE, the linear equation between CNE and HFNIHL prevalence rate for the non-Gaussian noise group almost overlapped with that for the Gaussian noise group, and the mean difference in HFNIHL prevalence rate between the two groups decreased from 9.7% to 1.4% (P<0.05). Conclusion Noise kurtosis is an effective metric for NIHL evaluation. Kurtosis-adjusted CNE can effectively evaluate occupational hearing loss due to non-Gaussian noise exposure in furniture manufacturing workers, and is expected to be a new indicator of non-Gaussian noise measurement and assessment.