Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.

ObjectiveTo investigate the characteristics and distribution of traditional Chinese medicine （TCM） syndromes in the patients with esophageal squamous cell carcinoma （ESCC）. MethodsAn electronic questionnaire was developed to collect the general data and four examination information of ESCC patients treated in 10 areas with high incidence of esophageal cancer in China from June 2020 to March 2021. Multiple analyses including frequency analysis， factor analysis， and hierarchical cluster analysis were performed to analyze the potential syndrome elements， disease location， and common syndromes of ESCC. ResultsA total of 2 027 patients with ESCC were included. Statistical analysis was performed on 113 symptoms， physical signs， 33 tongue manifestation variables， and 23 pulse manifestation variables of the patients’ four examination information. Factor analysis was performed on 55 variables with frequency>10%， extracting 19 common factors. According to clinical experience and expert opinions， the main lesions of patients with ESCC were in the spleen and stomach， and the main syndrome elements were Qi stagnation， blood stasis， phlegm， dampness， and Qi deficiency， with the syndrome element combination of phlegm obstruction + Qi stagnation + blood stasis being the most common. The syndromes can be classified into four categories of liver-stomach disharmony + combined phlegm and Qi obstruction， kidney-spleen dysfunction + combined phlegm and stasis， spleen-kidney Yang deficiency + obstinate phlegm and blood stasis， and liver-kidney Yin deficiency + obstinate phlegm and blood stasis. The main syndrome of ESCC was liver-stomach disharmony + combined phlegm and Qi obstruction in the early stage， liver-spleen dysfunction + combined phlegm and stasis in the middle stage， and spleen-kidney Yang deficiency + obstinate phlegm and blood stasis in the late stage. ConclusionESCC mainly has main pathological features of internal deficiency and external excess and combined deficiency and excess， with the key syndrome elements being phlegm obstruction， Qi stagnation， and blood stasis. The main disease locations are in the spleen and stomach， involving the liver， kidney， chest and diaphragm， heart， and lung. The main syndrome is liver-stomach disharmony + combined phlegm and Qi obstruction. In clinical practice， it is necessary to grasp the pathogenesis dynamics of the disease and use prescriptions according to patients’ syndromes.

Objectives:To explore the impact of inositol-requiring enzyme 1(IRE1)signaling pathway on autophagy flux and cardiac function in mice with myocardial ischemia/reperfusion(I/R)injury. Methods:H9c2 cells were divided into control group,IRE1 group,oxygen glucose deprivation/reoxygenation(OGD/R)group,OGD/R+IRE1 group,chloroquine group,IRE1+chloroquine group,OGD/R+IRE1+chloroquine group,OGD/R+chloroquine group,OGD group,OGD+chloroquine group,OGD+IRE1+RNAi X-box binding protein 1(si-XBP1)group and OGD+IRE1+XBP1 overexpression(XBP1-OE)group.Autophagy flux of cells in each group was evaluated by autophagy double-labeled adenovirus(Adv-RFP-GFP-LC3).The nuclear translocation of X-box binding protein 1(XBP1)was analyzed by immunofluorescence and western blot.Adult male C57BL/6 J mice were randomly divided into sham operation group,I/R group,IRE1 group and I/R+IRE1 group(n=8 each).Cardiac function was evaluated by echocardiography.Quantitative western blot analysis was used to detect protein expression of autophagy-related molecules. Results:(1)Compared with OGD/R group,the expression level of IRE1 protein was significantly upregulated(P<0.001),and the expressions of microtubule-associated proteins light chain 3B(LC3Ⅱ)and sequestosome 1(p62)proteins were significantly decreased in IRE1+OGD/R group(all P<0.05).Compared with OGD/R+chloroquine group,the expression of LC3Ⅱ and p62 protein was significantly increased in OGD/R+IRE1+chloroquine group(all P<0.05).Compared with control group,the fluorescence intensity ratio of IRE1 nucleus/cytoplasm was significantly increased in OGD/R group(P<0.001),and further increased in IRE1+OGD/R group(P<0.001).The level of XBP1 in the nuclear protein was significantly higher in IRE1+OGD/R group than in OGD/R group(P<0.01).Compared with OGD/R+IRE1 group,the yellow punctures was significantly decreased in OGD/R+IRE1+si-XBP1 group(P<0.01),and significantly increased in OGD/R+IRE1+XBP1-OE group(P<0.05).(2)Compared with Sham group,the left ventricular ejection fraction(LVEF)and fractional shortening(FS)were significantly decreased in I/R group(both P<0.05),LVEF and FS reduction could be partly reversed in I/R+IRE1 group.Compared with Sham group,the number of autophagic vacuoles and the expressions of IRE1,LC3Ⅱ and p62 were significantly increased in I/R group(P<0.05).The number of autophagic vacuoles and the expression of p62 were significantly downregulated(both P<0.05),and the expressions of IRE1 and LC3Ⅱ in myocardial tissue were further increased in I/R+IRE1 group as compared to the I/R group(all P<0.05). Conclusions:IRE1 restores the blocked autophagy flux induced by OGD/R and I/R by promoting the nuclear translocation of XBP1,and the recovery of autophagy flux is associated with cardiac function improvement post I/R injury in mice.

Objective To investigate the effect and possible mechanism of Emodin on Doxorubicin(DOX)-induced cardiotoxicity.Methods H9C2 cells were preincubated with low,medium and high doses(5,15 and 25 μmol·L-1)of Emodin for 8 h,and then cardiomyocytes were treated with 2.5 μmol·L-1 DOX for 16 h to establish a cardiotoxic injury model.MTT assay was used to detect the cell survival rate.The levels of cardiac troponin(cTnT),lactate dehydrogenase(LDH),creatine kinase(CK),superoxide dismutase(SOD),reactive oxygen species(ROS),malondialdehyde(MDA),reduced glutathione(GSH),glutathione peroxidase(GSH-Px)and the activities of Caspase-3 and Caspase-9 in H9C2 cells were detected by kit;RT-qPCR was used to detect miR-29a-5p and vascular endothelial growth factor-B(VEGFB)expression levels.The expression levels of VEGFB protein and other apoptosis-related factors were detected by Western blot.After transfection of miR-29a-5p mimics and inhibitors,the targeting of VEGFB to miR-29a-5p was detected by RT-qPCR and Western blot.H9C2 cells were transfected with miR-29a-5p mimics,Under the dose of Emodin 15 μmol·L-1,the activity of H9C2 cells was detected by MTT method,and the expression levels of miR-29a-5p and VEGFB were detected by RT-qPCR and Western blot.Results Compared with the DOX group,Emodin low,medium and high dose groups significantly increased the activity of H9C2 cells(P<0.05,P<0.01),and decreased the levels of cTnT,LDH and CK(P<0.05,P<0.01);RT-qPCR indicated that the expression level of miR-29a-5p decreased significantly and the expression level of VEGFB increased significantly(P<0.05,P<0.01);The levels of ROS and MDA decreased significantly,and the levels of GSH and GSH-Px increased significantly(P<0.05,P<0.01);TUNEL positive cells decreased significantly,and the activities of Caspase-3 and Caspase-9 decreased significantly.Western blot showed that the expression level of VEGFB increased significantly,the expression level of apoptosis-related factor Bax decreased significantly,and the expression levels of Bcl-2 and Bcl-xl increased significantly(P<0.05,P<0.01).After transfection with miR-29a-5p mimics and inhibitors,the expression of VEGFB decreased and increased respectively(P<0.05,P<0.01).After transfection of miR-29a-5p mimics and treatment with Emodin 15 μmol·L-1 of H9C2 cells,the significant decrease in the activity of H9C2 cells induced by DOX was reversed,and the significant decrease in the expression level of VEGFB was also reversed(P<0.05,P<0.01).Conclusion Emodin significantly reduces DOX-induced cardiotoxicity by regulating miR-29a-5p/VEGFB-mediated cardiomyocyte apoptosis.

Humans ; Cardiac Resynchronization Therapy ; Cardiac Pacing, Artificial ; Heart Ventricles ; Heart Failure/therapy* ; Treatment Outcome ; Electrocardiography ; Ventricular Function, Left

【Objective】 To investigate the relationship between the level of thrombin-antithrombin complex (TAT)/α2-plasmin inhibitor-plasmin complex (PIC) and the utilization rate of mechanical ventilation (MV) in critically ill patients. 【Methods】 For the cross-sectional study, adult patients who had been admitted to the intensive care unit (ICU) for one day or longer and had a record of the first four tests for thrombosis were enrolled. Age, gender, the results of TAT and PIC, disseminated intravascular coagulation score, treatment, and diagnostic information were retrospectively collected from the hospital information system and laboratory information system. Logistic regression model was used to explore the relationship between TAT/PIC and the MV utilization rate. Interaction analysis and subgroup analysis were conducted to explore whether there was any difference between patients with different age and gender, patients with/without DIC, and with/without infection. 【Results】 A total of 1 176 patients were enrolled in this study. The median of the first TAT/PIC was 15.84 (8.13-33.11) in all the patients. The multivariable Logistic regression model results showed that for every 5 increase in TAT/PIC, the possibility of using MV increased by 2.9% (OR=1.029, 95% CI: 1.008-1.050), and the possibility of using MV in Q3 patients was 1.566 times than that in Q1 patients (OR=1.566, 95% CI: 1.095-2.239); the possibility of using MV in Q4 patients was 2.457 times than that in Q1 patients (OR=2.457, 95% CI: 1.694-3.563). Interaction results showed that the relationship between the level of TAT/PIC and MV usage was different in patients with and without infection (Pinteraction=0.02). Further subgroup analysis showed that in the infected patients (674 cases), the possibility of using MV increased by 5.9% for every 5 increase in TAT/PIC (OR=1.059, 95% CI: 1.022-1.097, P=0.001), while there was no significant difference between different TAT/PIC and MV usage in non-infected patients (502 cases) (OR=1.012, 95% CI: 0.984-1.040, P=0.405). 【Conclusion】 There is a correlation between the level of TAT/PIC and mechanical ventilation in patients with infection in the ICU.

Objective:To identify the risk factors for postoperative nausea and vomiting (PONV) in the patients undergoing thoracic surgery.Methods:The medical records of patients of either sex, aged 18-80 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, underwent elective thoracic surgery from January 2018 to January 2020, were collected retrospectively.The age, gender, educational background, American Society of Anesthesiologists physical status, motion sickness, history of smoking, history of drinking, history of heart disease, history of hypertension, history of diabetes, preoperative blood routine, liver function, parameters of electrolytes; operation method, type of operation, operation time, intraoperative nerve block, consumption of dexamethasone before anesthesia induction and intraoperative sufentanil and dexmedetomidine, use of postoperative patient-controlled intravenous analgesia (PCIA), and postoperative rescue opioid analgesics and antiemetics were recorded.The patients were divided into PONV group and non-PONV group depending on the occurrence of nausea and vomiting within 24 h after operation.PONV group was further divided into nausea group (PON group) and vomiting group (POV group) according to whether vomiting occurred.Logistic regression analysis was used to identify the risk factors for PONV.Results:A total of 3 791 patients were enrolled in this study, with 144 cases in PONV group and 3 647 cases in non-PONV group.The incidence of PONV was 3.80%.There were 38 patients in POV group, and the incidence was 26.4%.The results of logistic regression analysis showed that motion sickness, female, pulmonary wedge resection, postoperative PCIA and increased use of postoperative rescue opioid analgesics were risk factors for PONV in the patients undergoing thoracic surgery, intraoperative use of dexmedetomidine was a protective factor for PONV; motion sickness, female and history of hypertension were risk factors for postoperative vomiting in the patients at risk for PONV ( P<0.05). Conclusions:Motion sickness, female, pulmonary wedge resection, postoperative PCIA, and increased use of postoperative rescue opioid analgesics are risk factors and intraoperative use of dexmedetomidine is a protective factor for PONV in the patients undergoing thoracic surgery; motion sickness, female and history of hypertension are risk factors for postoperative vomiting in the patients at risk for PONV.

Primary liver cancer has the features of high malignancy, rapid progression, frequent recurrence/metastasis, and high mortality, and therefore, most patients have developed intrahepatic or extrahepatic metastasis when attending the hospital and thus lost the opportunity for surgical treatment. Chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved good efficacy in the treatment of B-cell acute lymphoblastic leukemia, and clinical trials have been initiated to explore its applications in solid tumors such as primary liver cancer, pancreatic cancer, gastric cancer, and prostate cancer. This article reviews the efficacy of CAR-T immunotherapy in the clinical trials for primary liver cancer and discusses the difficult issues that need to be solved in clinical practice, such as the lack of suitable tumor targets, the inhibitory effect of tumor microenvironment on CAR-T cells, and the poor infiltration of CAR-T cells in tumor tissue, so as to provide a reference for related clinical studies.

Objective:To identify the risk factors for postoperative sleep disturbances in elderly patients undergoing thoracic surgery.Methods:A total of 200 elderly patients of both sexes, aged>65 yr, of American Society of Anesthesiology physical status Ⅱ or Ⅲ, scheduled for elective thoracic surgery, were enrolled in the study.Data regarding patient age, gender, body mass index (BMI), American Society of Anesthesiologists physical status, history of hypertension, history of diabetes mellitus, operation method, type of operation, operation time, intraoperative blood loss, use of intraoperative nerve block and use of dexmedetomidine in patient-controlled intravenous analgesia (PCIA) were collected.The patients were followed up after operation, the occurrence of postoperative pain at 48 h after operation was recorded, and patients′ subjective sleep quality at 48 h after operation was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). Patients were divided into 2 groups according to PSQI score: non-postoperative sleep disturbances group (PSQI score<5) and postoperative sleep disturbances group (PSQI score≥5). A multivariate logistic regression was used to identify the risk factors for postoperative sleep disturbances in elderly patients undergoing thoracic surgery.Results:A total of 169 patients were included in this study, and the incidence of postoperative sleep disturbances was 45%.The results of logistic regression analysis showed that history of preoperative insomnia, BMI≥24 kg/m 2, diabetes mellitus, thoracic surgery, radical resection of lung cancer, radical resection of esophageal cancer, operation time≥120 min and moderate and severe postoperative pain were risk factors for postoperative sleep disturbances in elderly patients undergoing thoracic surgery, and use of intraoperative nerve block and use of dexmedetomidine during PCIA were protective factors for postoperative sleep disturbances in elderly patients ( P<0.05). Conclusion:History of preoperative insomnia, BMI≥24 kg/m 2, diabetes mellitus, thoracic surgery, radical resection of lung cancer, radical resection of esophageal cancer, operation time≥120 min, moderate and severe postoperative pain are risk factors and use of intraoperative nerve block and use of dexmedetomidine during PCIA are protective factors for postoperative sleep disturbances in elderly patients undergoing thoracic surgery.

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.