ObjectiveTo investigate the impact of hepatocellular carcinoma （HCC） on the prognosis of patients with liver cirrhosis undergoing emergency endoscopic therapy for esophagogastric variceal bleeding， as well as independent influencing factors for the prognosis of liver cirrhosis patients without HCC after emergency endoscopic therapy for esophagogastric variceal bleeding. MethodsA total of 117 liver cirrhosis patients without HCC and 119 liver cirrhosis patients with HCC who underwent emergency endoscopic therapy for esophagogastric variceal bleeding in Renmin Hospital of Wuhan University from January 2017 to July 2023 were enrolled. Basic information including age and sex was collected from all patients， as well as the presence or absence of chronic diseases such as hypertension， diabetes， and coronary heart disease， the time of emergency endoscopy after admission， and liver function parameters including international normalized ratio， albumin， creatinine， sodium， total bilirubin， alanine aminotransferase， and aspartate aminotransferase （AST）. The independent-samples t test was used for comparison of normally distributed continuous variables between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous variables between two groups； the chi-square test was used for comparison of categorical variables between groups. The covariance analysis and the multivariate logistic regression analysis were used for comparison of outcome variables after control of baseline variables， and the Kaplan-Meier survival curve was plotted for each group. The univariate and multivariate Cox regression analyses were performed for survival time in the non-HCC group to investigate the independent influencing factors for survival time， and then the Kaplan-Meier curve analysis and the log-rank test were performed to validate such independent influencing factors and analyze the independent influencing factors for secondary outcomes. ResultsCompared with the non-HCC group， the HCC group had significantly higher red blood cell transfusion units （6.00［2.00～9.00］ vs 4.00［1.75～7.00］， Z=-2.050， P=0.040， F=4.869， adjusted P=0.028）， a significantly shorter survival time （29.77±16.01 days vs 38.07±11.43 days， t=4.574， P<0.001， F=17.294， adjusted P<0.001）， and a significantly higher 5-day rebleeding rate （22.69% vs 6.84%， χ²=11.736， P<0.001， adjusted P=0.021）. The Kaplan-Meier curve analysis showed that the risk of 42-day mortality in the HCC group was 3.897 （95% confidence interval ［CI］： 2.338 ‍— 6.495， P<0.001） times that in the non-HCC group. The multivariate Cox regression analysis of the non-HCC group showed that the total length of hospital stay （hazard ratio ［HR］=0.793， 95%CI： 0.644 ‍— ‍0.976， P=0.029） was an independent protective factor for 42-day survival. The Kaplan-Meier curve analysis showed that a length of hospital stay of >9 days was beneficial for the prognosis of patients （HR=4.302， 95%CI： 1.439 — 12.870， P=0.037）. Blood sodium level （odds ratio ［OR］=0.523， 95%CI： 0.289 ‍— ‍0.945， P=0.032） and MELD-Na score （OR=0.495， 95%CI： 0.257 ‍— ‍0.954， P=0.036） were independent protective factors against 5-day rebleeding， while AST level was an independent risk factor for 5-day rebleeding （OR=1.023， 95%CI： 1.002 ‍— ‍1.043， P=0.028） and in-hospital death （OR=1.036， 95%CI： 1.001‍— ‍1.073， P=0.045）. ConclusionLiver cirrhosis patients with variceal bleeding and HCC tend to have a worse prognosis， and for the non-HCC group， in-hospital mortality rate increases with the increase in AST level. The total length of hospital stay is an independent protective factor for survival time in the non-HCC group， and it is recommended to appropriately prolong the length of hospital stay for such patients.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Objective To investigate the changes of serum cardiac-specific troponin I (cTnI) level in patients after lung transplantation. Methods Clinical data of patients undergoing lung transplantation in our hospital from December 2016 to December 2022 were retrospectively analyzed. The relationship between postoperative serum cTnI level and clinical characteristics were explored. Results Finally 20 patients were collected, including 15 males and 5 females with an average age of (51.65±12.79) years. The serum cTnI level was significantly increased after lung transplantation. The serum cTnI reached the highest level on the first day after transplantation, and significantly decreased from the third day after transplantation. The serum cTnI levels in patients with obstructive pulmonary disease and bilateral lung transplantation were significantly higher than those in patients with restrictive pulmonary disease and unilateral lung transplantation on the day after surgery and on the first day after transplantation. Conclusion Transient myocardial injury can occur after lung transplantation, which is characterized by an abnormal increase in serum cTnI level.

OBJECTIVE: To establish the dynamic treatment strategy of Chinese medicine (CM) for metastatic colorectal cancer (mCRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for mCRC. METHODS: From the outpatient cases of mCRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese Medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment (CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment (CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for mCRC was explored based on the cost-sensitive classification learning algorithm for survival (CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. RESULTS: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for mCRC was established based on CSCLSurv. Different CM intervention strategies for mCRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the model-recommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months (P=0.06). CONCLUSIONS The dynamic treatment strategy of CM, based on CSCLSurv for mCRC, plays a certain role in providing clinical hints in CM. It can be further improved in future prospective studies with larger sample sizes.
Humans ; Colorectal Neoplasms/therapy* ; Machine Learning ; Female ; Male ; Middle Aged ; Neoplasm Metastasis ; Algorithms ; Medicine, Chinese Traditional/methods* ; Aged ; Adult ; Kaplan-Meier Estimate

Aim To investigate the effects of dagliflozin (DAPA) on atrial tachyarrhythmia (AT) in rats with right heart failure (RHF) due to pulmonary arterial hypertension (PAH) and the underlying mechanisms. Methods Sixty male SD rats were randomly divided into four groups: control group (CTL group), model group (MCT group), MCT + low-dose DAPA intervention group (MCT + LD group) and MCT + high-dose DAPA intervention group (MCT + HD group). After 35 days of continuous intervention, the model and cardiac function evaluation, atrial structural remodelling assessment, inflammatory factor detection, and in vivo cardiac electrophysiology experiments were completed. Results DAPA reduced menn pulmonaryarterial pressure (mPAP) and menn right ventricular pressure (mRVP) in the model rats (P <0.05), attenuated the inflammatory response (P < 0.05), reduced right atrial fibrosis (P <0.05), reduced AT induction rate (P < 0.05) and mean atrial tachyarrhythmia duration (MATD) (P < 0.05), the extent of which was more pronounced in the high-dose DAPA intervention group. Conclusions DAPA can reduce AT susceptibility in PAH-induced RHF rats, and the mechanisms may be related to the inhibition of systemic inflammation and anti-atrial fibrosis by DAPA.

Retinal vascular bed area(RVBA)is the total area of retinal vasculature segmented by ultra-widefield fluorescein angiography(UWFA)images, and is an objective absolute value in square millimeter. RVBA is mainly affected by the diameter and length of retinal vessels, and whether RVBA increases or decreases depends on the “competition” between ischemia and angiogenesis, indicating subtle changes in retinal vascular morphology. As a new indicator for the study of retinal vascular diseases, RVBA may have higher stability and accuracy than the ischemia index(ISI)and non-perfusion area(NPA). RVBA is currently mainly used to evaluate the progression and prognosis of diabetic retinopathy(DR). It was found that retinal total RVBA in DR eyes was greater than the normal eyes and it decreased in DR eyes after anti-vascular endothelial growth factor(VEGF)treatment. These findings provide favorable support for the study of microvascular lesions in DR. In this article, the application of RVBA in DR was reviewed to provide a reference for the clinical study of RVBA in other retinal vascular diseases such as retinal vein occlusion(RVO).

【Objective】 To investigate the feasibility of laparoscopic simple prostatectomy (LSP) in the treatment of large volume benign prostate hyperplasia (BPH). 【Methods】 Clinical and follow-up data of 30 patients with large volume BPH treated with LSP in our hospital during Feb.2019 and Dec.2021 were retrospectively analyzed. All patients underwent extraperitoneal LSP operation. The perioperative and 1-12 month postoperative follow-up data were analyzed. 【Results】 The average prostate volume was (92.4±38.9) mL, operation time (125±45) min, and weight of resected prostate (60.25±16.90) g. The hemoglobin decreased by (12.21±7.25) g/d after operation. No blood transfusion was needed. There was no need for bladder irrigation after operation in 21 cases (70%), and 9 cases (30%) had bladder irrigation time of (0.95±0.49) d. The postoperative catheter indwelling time was (6.92±2.51) d, and hospital stay (5.36±1.63) d. During the follow-up of (9.25±5.4) months, there was 1 case of postoperative intestinal obstruction (Clavien-Dindo grade II), 1 case of transient urinary incontinence (Clavien-Dindo grade I), and 1 case of delayed hematuria (Clavien-Dindo grade I). No urethral stricture occurred. The maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), International Prostate Symptom Score (IPSS) and quality of life (QoL) 3 months after operation were significantly improved compared with those before operation (P<0.05). There was no significant difference in sexual function before and after operation (P>0.05). 【Conclusion】 LSP is safe and effective in the treatment of large volume BPH. It has advantages of complete resection of glands, minor bleeding and short postoperative bladder irrigation time. However, it still needs to be confirmed by a prospective control study of large samples.

Esophageal cancer is a common and poorly prognostic cancer, and early screening and early diagnosis arc the keys to improve the prognosis of patients. In recent years, more and more studies have shown that changes in gastrointestinal flora are associated with the occurrence, progression, recurrence, metastasis and chemotherapy resistance of esophageal cancer. This article mainly reviewed the changes of gastrointestinal flora in esophageal cancer patients and the progress of research on gastrointestinal flora in the screening, diagnosis and prognosis of esophageal cancer.