ObjectiveAccording to the etiology， pathogenesis， and clinical characteristics of dry eye （DE）， this paper aims to analyze existing DE animal models to provide recommendations for building more clinically relevant DE models that integrate traditional Chinese and Western medicine. MethodsBy the retrieval and analysis of relevant literature on DE animal experiments， combined with expert consensus， an evaluation scale was created to assess relevance from the perspectives of pathogenesis， diagnostic criteria， and traditional Chinese medicine （TCM） differentiation. On the basis of data provided by the literature， the clinical relevance was evaluated for the animal models constructed in the literature. ResultsAmong the existing methods for establishing a DE animal model， benzalkonium chloride eye-drop induction showed the highest clinical relevance， demonstrating 98% alignment with Western medicine. However， current models generally showed higher relevance to Western medicine than to TCM， and there was a lack of models integrating disease with syndrome. ConclusionAs DE involves diverse causes and pathogenesis， single-factor models cannot fully simulate the complex pathology of DE. Future research should focus on building multi-mechanism DE models， exploring new etiological directions， standardizing model evaluation systems， and promoting integration of traditional Chinese and Western medicine. This will help precisely simulate the pathophysiological process of human DE and provide more valuable guidance for clinical diagnosis and treatment， ultimately enhancing patient outcomes and satisfaction.

OBJECTIVE To explore the effect and mechanism of warming channels and activating blood circulation external treat-ment to alleviate peripheral hyperalgesia in knee osteoarthritis(KOA)based on NGF/TrKA signaling pathway.METHODS 30 SD rats were randomly divided into normal group,KOA group and Yiceng group.KOA model was established by anterior cruciate ligament transection(ACLT).14 days after model establishment,rats in Yiceng group were treated with Yiceng patch.The peripheral pain threshold of rats was measured at different time points.The cartilage sections were stained with HE,Aggrecan and type II collagen.The synovial sections were stained with HE,Sirius red,silver and performed with immunostaining.The protein expression of key molecules NGF and TrKA of NGF/TrKA signaling pathway,inflammatory index IL-1β,pain mediator TRPV1,pan-neural mark-ers PGP9.5 and S100 in synovium and complexes transported to dorsal root ganglia(DRG)tissues via nerve endings was determined by Western Blot.The corresponding gene expression was determined by qPCR.The levels of NGF and SP in peripheral blood of rats were determined by ELISA.RESULTS Compared with the KOA group,the cold allodynia and mechanical allodynia thresholds of the rats in the Yiceng group increased(P<0.05,P<0.01);the protein and gene expression of NGF,TrKA,TRPV1,IL-1β,PGP9.5 in the synovial tissue decreased(P<0.05,P<0.01);the protein and gene expression levels of TRPV1,PGP9.5,S100 in the DRG tissue were downregulated(P<0.05,P<0.01).CONCLUSION The warming channels and activating blood circulation external treatment can inhibit the NGF/TrKA signaling pathway,downregulate the gene and protein expressions of NGF,TrKA,TRPV1,IL-1β,PGP9.5,and may inhibit the sprouting of sensory nerve fibers and improve the peripheral hyperalgesia state of rats with KOA.

Objective To investigate the optimal adaptation period for mice at different developmental stages during metabolic cage experiments, aiming to provide a reference for conducting metabolic research using mice. Methods A total of 80 male C57BL/6J mice at three developmental stages (weaning period M1, adolescent M2, and adulthood M3) were subjected to a 7-day metabolic cage experiment. Data on food intake, water intake, energy expenditure, respiratory quotient, body weight, and activity levels were recorded every five minutes. The collected data were processed using time series decomposition and comprehensive cluster analysis. Statistical differences were compared using repeated measures ANOVA combined with t-test to determine the optimal adaptation period. Results Significant differences in metabolism were observed among mice in different developmental stages (P<0.01). Compared with adolescent (M2) and adult (M3) mice, weaned mice (M1) exhibited lower activity level (P<0.01) and less distinct circadian rhythm. M1 mice had higher oxygen consumption, carbon dioxide production, and energy expenditure, as well as a lower respiratory quotient (all P<0.001), indicating that they mainly relied on fat as an energy source. Analysis of food intake, water intake, and energy expenditure revealed significant differences between the first light cycle (0-12 h) and the second light cycle (24-36 h) across all developmental stages (all P<0.05) . However, there was no significant difference in daily food intake or water intake after 24 hours (both P>0.05). Comprehensive cluster analysis of multiple indicators showed that the overall indicators of mice during the first 24 hours in the metabolic cages did not cluster with those of the subsequent 6 days, demonstrating significant differences. Conclusion Metabolic cage experiment can be used to detect continuous physiological changes in mice. The results suggest that mice can adapt to new metabolic cages environment within 24 hours, providing a theoretical basis for the design of metabolic experiments using mice.

Percutaneous dilatational tracheostomy (PDT) is a surgical method for quickly establishing an artificial airway, which has been favored by clinicians because of its simple operation, small trauma and bedside operation. However, for patients with tracheal intubation in intensive care unit (ICU), the tip and balloon of the existing endotracheal tube will not only hinder percutaneous puncture, but also hinder insertion of guidewire and tracheotomy tube, and consequently affect the process of PDT. On the contrary, blind withdrawal of the existing endotracheal tube may cause the tracheal tube tipleave the glottis, leading to an emergency airway situation that endangers the patient's life. Therefore, the medical staff from intensive care medicine department of the First People's Hospital of Chenzhou designed a laryngeal mask and its monitoring device, which is convenient for withdrawal of endotracheal tube, and obtained the national utility model patent of China (patent number: ZL 2020 2 2795887.1). The device is composed of a laryngeal mask and a monitoring device. The laryngeal mask mainly includes a laryngeal mask body, a vent tube, a guidance tube and other components. The laryngeal mask body is mainly used to seal the throat and provide the air supply channel for the patient together with the ventilation tube. The main function of the guidance tube is to accommodate the tracheal tube and facilitate the withdrawal of the inserted tracheal tube. During percutaneous dilatation tracheotomy, this device can monitor the withdrawal of tracheal catheter in real time, and immediately ensure the airway patency of patients without re-intubation when the cuff of tracheal catheter exits the glottis. The utility model has the advantages of real-time monitoring, simple operation, safety and convenience, and is worthy of transformation and promotion.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective:To investigate the efficacy of plasma exchange (PE) in treatment of patients with acute respiratory distress syndrome (ARDS).Methods:Forty-two patients who met the inclusion criteria in the intensive care unit of Chenzhou First People′s Hospital were randomly divided into control group and plasma exchange (PE) group with 21 cases in each group. The control group received conventional treatment; while the PE group received conventional treatment plus PE. The mechanical ventilation time (MVT), length of ICU stay (ICU LOS), 28-day mortality and 90-day mortality of patients were analyzed. The oxygenation index, SOFA score, norepinephrine (NE) dose, C-reactive protein (CRP), procalcitonin (PCT) and IL-6 levels were evaluated before and after treatment.Results:In the control group the oxygenation index, IL-6, PCT and CRP were significantly improved after treatment ( t=-4.50, 2.46, Z=-3.53, t=5.55, all P<0.05), but the SOFA score and NE dose were not significantly changed ( t=1.98, Z=-0.47,all P>0.05). In the PE group, the oxygenation index, SOFA score, IL-6, PCT, CRP were significantly improved and the NE dose was reduced after treatment ( t=2.18, 9.23, 5.26, Z=-3.77, t=7.27 and Z=-2.54,all P<0.05). The oxygenation index, SOFA score, IL-6, CRP were significantly better after treatment and NE dose was lower in PE group than those in the control group ( t=2.18, -2.21, -2.12, -2.61 and Z=-2.11, all P<0.05). Compared with the control group, the MVT(14.0±5.2d vs. 18.4±6.3d), ICU LOS(19.3±4.9d vs. 23.2±7.3d) and 28-day mortality (14.3%(3/21) vs. 42.8%(10/21)) in the PE group were significantly decreased ( t=-2.48, -2.04 and χ2=4.20,all P<0.05). There was no significant difference in the 90-d mortality between the two groups (28.6%(6/21) vs. 52.4%(11/21), χ2=2.47, P=0.208). Conclusion:Therapeutic plasma exchange can significantly reduce the inflammatory response, improve the organ function and reduce the short-term mortality of ARDS patients.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

This study was aimed to investigate the effect of traditional Chinese medicine (TCM) compound "Ji-Sui-Kang (JSK)" on the differentiation of neural stem cells (NSCs).Drug serum of JSK was prepared.The primary NSCs were isolated and cultured.NSCs were identified.Fetal bovine serum (FBS) was used to induce differentiation of NSCs.Different doses of drug serum of JSK was added to intervene the differentiation.There were the high-,medium-,and low-dose group.The blank control group was also set.The β Ⅲ-tubulin and GFAP were used to detect the differentiation of NSCs.And then,it was compared with the control group without drug serum.Positive cells ofβ m-tubulin and GFAP in different visual fields were counted.And the percentage of positive cells in the total number of cells was calculated.Fluorescence microscope was used to conduct quantitative fluorescence experiments.The results showed that the cultured neurospheres were expressed of Nestin protein.The percentage ofβⅢ-tubulin positive cells in the high-,medium-and low-dose group of drug serum of JSK was significantly higher than that in the control group (P＜0.05).The percentage of GFAP positive cells in the high-,medium-and low-dose groups of drug serum of JSK was significantly lower than that in the control group (P＜0.05).And the high-dose group of drug serum of JSK was statistically significant compared with the middle-and low-dose group of drug serum of JSK (P＜0.01).It was concluded that TCM compound JSK promoted thedifferentiation of NSCs intoβⅢ-tubulin positive cells.It provided a basis for treatment of SCI with TCM.