ObjectiveTo evaluate the effectiveness of exhalation-inhalation exercise on early pulmonary rehabi-litation for patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. MethodsA total of 120 participants with AECOPD were randomly divided into a treatment group and a control group， with 60 participants in each group. The control group treated with conventional western medicine， while the treatment group received exhalation-inhalation exercise training on the basis of conventional western medicine treatment， with 30 minutes per session and 5 sessions per week. The course of treatment for both groups was 12 weeks. The primary outcome was the 6-minute walking distance （6MWD）. The secondary outcomes included pulmonary function indexes including forced expiratory volume in one second/forced vital capacity （FEV1/FVC）， percentage of predicted forced expiratory volume in one second （FEV1%） and percentage of predicted forced vital capacity （FVC%）， St.George's Respiratory Questionnaire （SGRQ） score， modified Medical Research Council （mMRC） dyspnea scale score， COPD assessment test （CAT） score， hospital anxiety and depression scale-anxiety subscale ［HADS（A）］ score， and hospital anxiety and depression scale-depression subscale ［HADS（D）］ score. Meanwhile， safety of all participants was recorded and assessed. ResultsDuring the treatment， 12 participants dropped out from both the treatment group and the control group， with 48 participants in each group finally included in the analysis. The 6MWD of both groups after treatment was higher than that before treatment， and the 6MWD of the treatment group was higher than that of the control group （P＜0.05 or P＜0.01）. After treatment， the SGRQ score， mMRC score and CAT score of the treatment group were lower than those before treatment， while FEV1%， FVC% and FEV1/FVC were higher than those before treatment （P＜0.05）. Moreover， after treatment， the FEV1/FVC of the treatment group was higher than that of the control group， while the SGRQ score， mMRC score and CAT score were lower than those of the control group （P＜0.05 or P＜0.01）. There was no statistically significant difference in pulmonary function indexes， SGRQ score， mMRC score and CAT score after treatment in the control group （P＞0.05）. No statistically significant difference was observed in HADS（A） score and HADS（D） score after treatment within and between groups （P＞0.05）. The incidence of adverse reactions in the treatment group was 6.25% （3/48）， and 0 in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionExhalation-inhalation exercise for patients with AECOPD in early pulmonary rehabilitation can improve patients' exercise tole-rance， quality of life， clinical symptoms and pulmonary function， with good safety.

The excessive accumulation of advanced glycosylation end products(AGEs), the end products of non-enzymatic glycosylation reactions, can be involved in the pathological processes of various ocular diseases through mechanisms such as oxidative stress, inflammatory responses and apoptosis. In this paper, we systematically reviewed the key role of AGEs in diabetic keratopathy, cataract, glaucoma, age-related macular degeneration(ARMD)and diabetic retinopathy(DR). It was found that AGEs activate signalling pathways such as NADPH oxidase, MAPK and NF-κB by binding to the receptor RAGE, leading to reactive oxygen species(ROS)generation, release of inflammatory factors, and vascular endothelial dysfunction, which in turn induces delayed corneal healing, cross-linking of lens proteins, optic nerve degeneration, formation of choroidal neovascularisation(CNV), and blood-retinal barrier(BRB)disruption. For example, in diabetic keratopathy, AGEs delay wound healing via the ROS/NLRP3 inflammatory vesicle axis; in cataract, ascorbic acid-mediated cross-linking of lens proteins due to AGEs directly impairs lens transparency; and in DR, AGEs exacerbate microvascular damage by regulating vasucular endothelial growth factor(VEGF)expression and pericyte apoptosis. In addition, this article discusses the advances and limitations of AGEs detection techniques, such as the potential application of lens AGEscan fluorescence assay in screening for diabetic complications, and the need to develop tissue-specific assays for aqueous humour and vitreous. For therapeutic strategies, the research directions of inhibiting AGEs production, blocking RAGE signalling pathway and developing anti-glycosylation drugs are proposed to emphasise their clinical value in delaying disease progression. This review not only integrates the molecular mechanisms and clinical associations of AGEs in ocular diseases, but also provides a theoretical basis for targeted interventions, which is of great significance in exploring novel diagnostic and therapeutic strategies.

Objective:To explore the expressions of long noncoding RNA (lncRNA) homeobox A11 antisense RNA (HOXA11-AS) and lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) in hypopharyngeal carcinoma tissues and their relationships with prognosis.Methods:Prospectively, 80 patients with hypopharyngeal carcinoma who were treated in Handan Central Hospital from February 2019 to February 2021 were selected. The hypopharyngeal carcinoma tissues resected surgically and the adjacent normal tissues (more than 2 cm away from the edge of the cancer tissue) were obtained. The expressions of HOXA11-AS and LEF1-AS1 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues and adjacent normal tissues were compared. The relationships between their expressions and clinicopathological features were analyzed. The Kaplan-Meier method was used to analyze the relationships between high/low expressions of HOXA11-AS and LEF1-AS1 and the prognosis of patients with hypopharyngeal carcinoma.Results:The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were higher than those in adjacent normal tissues (all P<0.05). The expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were related to tumor node metastasis (TNM) stage, degree of differentiation, and lymph node metastasis (all P<0.05). The 3-year overall survival rates of patients with high expressions of HOXA11-AS and LEF1-AS1 in hypopharyngeal carcinoma tissues were lower than those of patients with low expressions (all P<0.05). Conclusions:The expressions of HOXA11-AS and LEF1-AS1 are increased in hypopharyngeal carcinoma tissues, which are related to poor prognosis of patients with hypopharyngeal carcinoma.

Acute lung injury （ALI） is one of the most common and critical diseases in clinical practice， with extremely high morbidity and mortality， seriously threatening human life and health. The pathogenesis of ALI is complex， in which the inflammatory response is a key factor. Studies have shown that NOD-like receptor protein 3 （NLRP3） inflammasomes are involved in ALI through mechanisms such as inflammation induction， increased microvascular permeability， recruitment of neutrophils， oxidative stress， and pyroptosis， playing a key role in the occurrence and progression of ALI. Therefore， regulating NLRP3 inflammasomes and inhibiting the release of inflammatory factors can alleviate the damage in ALI. At present， ALI is mainly treated by mechanical ventilation and oxygen therapy， which have problems such as high costs and poor prognosis. In recent years， studies have shown that traditional Chinese medicine （TCM） can reduce the inflammatory response and the occurrence of oxidative stress and pyroptosis by regulating the NLRP3 inflammasome， thus alleviating the damage and decreasing the mortality of ALI. Based on the relevant literature in recent years， this article reviews the research progress in TCM treatment of ALI by regulating NLRP3 inflammasomes， discusses how NLRP3 inflammasomes participate in ALI， and summarizes the active ingredients， extracts， and compound prescriptions of TCM that regulate NLRP3 inflammasomes， aiming to provide new ideas for the clinical treatment of ALI and the development of relevant drugs.

Objective To investigate the effects of miR-126 on myocardial remodeling and macrophage polarization after acute myocardial infarction(AMI).Methods(1)Twenty-one rats were divided into a sham operation group and an AMI group.The AMI group was further divided into postoperative days 1,3,5,7,9,and 11 days(AMI-1,AMI-3,AMI-5,AMI-7,AMI-9,AMI-11),with 3 rats in each group,and postoperative day 3 was selected for subsequent study.(2)Thirty rats were randomly divided into three groups:sham operation group,AMI group and miR-126 overexpression group,with 10 rats in each group.RT-qPCR was used to detect the expression levels of miR-126 mRNA.2,3,5-Triphenyltetrazole chloride(TTC)staining was used to detect the infarct size.Myocardial fibrosis was detected by Masson staining.The cross-sectional area of the myocardium was determined by H&E staining.Immunofluorescence staining was used to detect the protein levels of CD86 and CD206 in myocardial tissue.Western blotting was used to detect the protein levels of CD86 and CD206 in myocardial tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum were detected by ELISA kit.Results Compared with the sham operation group,the expression level of miR-126 mRNA in myocardial tissue of rats in the AMI group was significantly decreased on postoperative day 1(P<0.05),reached the lowest level on postoperative day 3.And then although it rose to a certain extent,it remained lower than that of the sham operation group on postoperative day 11(P<0.05),and postoperative day 3 was selected for further study.Compared with the sham operation group,the expression of miR-126 mRNA in myocardial tissue of the AMI group was decreased(P<0.05),and the myocardial fibrosis,infarct size and myocardial cross-sectional area were increased(P<0.05).The expression of CD86 protein in myocardial tissue was increased and the expression of CD206 protein was decreased(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were increased(P<0.05).Compared with the AMI group,the rats in the miR-126 overexpression group had a significant increase in the mRNA expression of miR-126 in myocardial tissue(P<0.05),a significant reduction in myocardial fibrosis,infarct size,and myocardial cross-sectional area(P<0.05),a significant reduction in the expression of CD86 protein in myocardial tissue,and a significant increase in the expression of CD206 protein(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05).Conclusion Over-expression of miR-126 can improve myocardial remodeling and promote M2 macrophage polarization in AMI rats.

Objective:To investigate the association between triglyceride glucose index (TyG) and early vascular aging measured by brachial ankle pulse wave velocity (baPWV) in young and middle-aged population.Methods:It was a cross-sectional study. A total of 5 680 subjects aged 20 to 59 years who underwent health check-ups at the Health Management Center of General Hospital of Tianjin Medical University from January to December in 2020 were selected as the research subjects. All the research subjects completed the health risk assessment questionnaire, physical examination, laboratory test, and multi-functional vascular lesion detection. The TyG was calculated and the research subjects were divided into four groups with the quartiles of TyG (Q 1 to Q 4, with a cut-off value of 8.22, 8.60 and 9.01, respectively). The baPWV value was converted into a Z-score, and those with a Z-score above the 95th percentile were defined as having early vascular aging. The Spearman correlation method, multiple linear regression model, binary logistic regression model and the area under the receiver operating characteristic curve (AUC) were used to analyze the association between TyG and early vascular aging. Results:Among the 5 680 middle-aged and young people included in the analysis, there were 3 117 males and 2 563 females, with an age of 46 (39, 52) years, a TyG of 8.60 (8.22, 9.01), and a baPWV of 1 279.25 (1 147.50, 1 434.25) cm/s. The prevalence rate of early vascular aging was 5.02% (285/5 680). Taking group Q 1 as the reference, in the multiple linear regression model adjusted for multiple factors, group Q 4 was significantly associated with a 47.64 (95% CI: 28.18-67.11) cm/s increase in baPWV ( P for trend<0.001). In the multivariate adjusted binary logistic regression model, compared with that in the Q 1 group, the OR of early vascular aging occurrence in the Q 2, Q 3, and Q 4 groups was 1.52 (95% CI: 0.75-3.07), 1.78 (95% CI: 0.89-3.58), and 3.04 (95% CI: 1.47-6.31), respectively. Elevated TyG level was positively correlated with the occurrence of early vascular aging ( P for trend<0.001). The AUC of TyG in predicting early vascular aging was 0.732 (95% CI: 0.704-0.759), with the optimal cut-off value being 8.86. The AUC of TyG in predicting early vascular aging in males was lower than that in females [0.665 (95% CI: 0.628-0.702) vs 0.796 (95% CI: 0.748-0.843)] ( P<0.001). Conclusions:There is a correlation between TyG and early vascular aging measured by baPWV in the middle-aged and young population. When TyG≥8.86, clinical intervention measures should be taken in a timely manner.

Objective:To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS).Methods:A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m 2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children′s Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results:Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m 2), t=-0.76, P>0.05)). No serious adverse reactions occurred in this study. Conclusion:RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Objective To explore the role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

Hepatocellular carcinoma(HCC),as the most common type of liver cancer,poses a significant threat to global public health due to its high incidence and mortality rates.This paper delves into the etiology,pathogenesis,and syndrome differentiation of liver cancer from the perspective of"dispersing qi and fortifying the body resistance",based on the clinical experience of renowned traditional Chinese medicine(TCM)practitioner,Prof.Changquan Ling.Prof.Ling believes that the development of liver cancer is closely related to the disruption of liver qi flow,the accumulation of blood stasis over time,and the generation of toxin from long-term stagnation,accompanied by pathological changes such as imbalance of yin and yang,deficiency of the body's vital qi and accumulation of pathogenic factors,and internal blazing of cancer toxins.In terms of treatment,he emphasizes the principles of dispersing qi and fortifying the body resistance,addressing both the root cause and symptoms.This is achieved by regulating the functions of viscera,improving the stagnation of qi flow,and supplemented by methods such as clearing heat and detoxifying,and softening and dispersing hard masses,aiming to break the vicious cycle of qi stagnation,deficiency of vital qi,and pathogenic factor generation,thereby promoting the recovery from the disease.Through detailed analysis of clinical cases,this paper demonstrates Prof.Ling's unique insights and significant efficacy in treating liver cancer through"dispersing qi"to"fortify the body resistance",ultimately achieving"tumor suppression".This provides new references and perspectives for the clinical diagnosis and treatment of liver cancer in TCM.

Objective To explore the role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.