COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

This study elucidates the pathogenesis and treatment strategies for tinnitus based on the theory of turbid toxin obstructing the orifices and by combining the theory of six-meridian syndrome differentiation.It is pointed out that turbid toxin is a pathogenic factor and a kind of pathological product arising from emotional disturbances,dietary irregularities,and metabolic dysfunctions,which leads to the dysfunction of zang-fu organs and meridians.The core pathogenesis of tinnitus is identified as turbid toxin obstructing the orifices.Following the theory of six-meridian syndrome differentiation,tinnitus can be treated in stages:in the early stage,tinnitus is attributed to shaoyang's failure in conveying and dispersing;in the progressive stage,tinnitus is due to taiyin's inability of transportation and transformation;in the late stage,tinnitus results from insufficient shaoyin failing in nourishment.Correspondingly,therapies of harmonizing shaoyang to expel pathogens,strengthening the spleen to eliminate turbidity,and nourishing the kidneys to resolve turbidity are performed with the modified use of Xiao Chaihu Decoction,Xiaoyao San combined with Shenling Baizhu San,and Erlong Zuoci Pills,respectively.The integration of the theory of turbid toxin obstructing the orifices and the theory of six-meridian syndrome differentiation not only enriches the traditional Chinese medicine pathogenesis of tinnitus,but also provides new insights for its clinical treatment.

Objective To observe the value of radiomics models based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced hepatobiliary phase(HBP)MRI for assessing clinical pathological stage of hepatic fibrosis(HF).Methods Data of 240 patients with pathologically/clinically diagnosed and clinical pathological staged HF who underwent Gd-EOB-DTPA enhanced MR examination were retrospectively analyzed.The liver-to-muscle signal intensity ratio(SIR1)and liver-to-spleen signal intensity ratio(SIR2)were measured based on HBP images.Radiomics features of HBP images were extracted and screened to construct radiomics models.The signal intensity ratio(SIR)-radiomics combined models were constructed based on SIR and radiomics signatures.Receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of each model for assessing clinical pathological stage of HF.Results The area under the curve(AUC)of SIR1 and SIR2 models for assessing clinical pathological stage of HF were 0.63-0.70 and 0.65-0.71,respectively.The most effective radiomics model for assessing HF,significant HF,advanced HF and early cirrhosis was support vector machine(SVM),SVM,light gradient boosting machine and K-nearest neighbor model,respectively,with the AUC in validation set of 0.87,0.82,0.81 and 0.80,respectively,while the AUC of SIR-radiomics combined models in validation set of 0.88,0.82,0.82 and 0.81,respectively.Conclusion The radiomics models based on Gd-EOB-DTPA enhanced HBP MRI were helpful for assessing clinical pathological stage of HF.Combining with HBP SIR could improve their efficacy.

Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.

Cerebrovascular diseases pose a serious threat to human health.According to the latest epidemiological data,stroke is one of the leading causes of death and disability among adults worldwide.Acute ischemic stroke(AIS),which is caused by local circulatory disorders in the brain,accounts for over 80%of all strokes and is the most common type of stroke.Due to extensive damage to the cerebral cortex or direct involvement of the autonomic nerve centers and pathways caused by AIS,the balance between the sympathetic and parasympathetic nervous systems is disturbed(with a predominance of sympathetic activation).Therefore,the organs targeted by the downstream pathways of the sympathetic and parasympathetic nervous systems are affected by the neurotransmitters they secrete,resulting in a range of systemic complications(such as cardiac complications,stroke-related infections,gastrointestinal complications,acute kidney injury,metabolic changes,and sexual dysfunction).These systemic pathological changes,in turn,affect the progression of AIS,thereby exacerbating brain damage or directly leading to patient death.Treatments targeting imbalances in the autonomic nervous system may play a role in reducing complications and improving the prognosis of AIS.This article reviews the systemic effects of autonomic dysfunction following AIS and its mechanisms,providing insights for the treatment of AIS and intervention of systemic complications.

Objective:To analyze the clinical efficacy of cetuximab combined with mFOLFOX6 chemotherapy regimen in the treatment of advanced colorectal cancer, to explore its effects on the distribution of T lymphocyte subsets, patients' physical status and tumor marker levels, and to analyze its safety.Methods:A total of 90 patients with advanced colorectal cancer admitted to the Hainan Cancer Hospital from April 2020 to April 2022 were selected and randomly divided into observation group ( n=45) and control group ( n=45) according to random number table method. The control group was treated with the mFOLFOX6 chemotherapy regimen, while the observation group was treated with cetuximab combined with the mFOLFOX6 chemotherapy regimen. Objective response rate (ORR), disease control rate (DCR), T lymphocyte subsets levels (percentages of CD3 +, CD4 +, CD8 +), Karnofsky performance status (KPS) score, tumor marker vascular endothelial growth factor (VEGF), endothelial cell-specific molecule 1 (ESM1), carcino-embryonic antigen (CEA) levels and the incidence of adverse reactions were compared between the two groups after treatment. Results:After 4 cycles of treatment, the ORR was 66.67% (30/45) in the observation group and 42.22% (19/45) in the control group, and there was a statistically significant difference ( χ2=5.42, P=0.020). The DCR of the observation group was 86.67% (39/45) and that of the control group was 66.67% (30/45), and there was a statistically significant difference ( χ2=5.03, P=0.025). The percentages of T lymphocyte subsets CD3 +, CD4 + and CD8 + in the observation group were (63.35±6.71) %, (35.67±3.96) % and (17.03±2.11) %, respectively, while those in the control group were (52.23±5.92) %, (30.55±3.51) % and (20.64±2.83) %, respectively. The percentages of CD3 + and CD4 + in the observation group were significantly higher than those in the control group ( t=8.34, P<0.001; t=6.49, P<0.001), while the percentage of CD8 + ratio was significantly lower ( t=6.86, P<0.001). The KPS score of the observation group was (95.55±9.74) points, and that of the control group was (85.03±8.92) points, and there was a statistically significant difference ( t=5.34, P<0.001). VEGF, ESM1 and CEA levels in the observation group were (303.45±33.21) ng/L, (75.66±8.36) pg/ml and (7.73±0.98) ng/ml, respectively, while those in the control group were (364.53±39.07) ng/L, (92.53±9.91) pg/ml and (9.95±1.13) ng/ml, respectively. VEGF, ESM1 and CEA levels in observation group were significantly lower compared with control group ( t=7.99, P<0.001; t=8.73, P<0.001; t=9.96, P<0.001). The total incidence of adverse reactions was 75.56% (34/45) in the observation group and 66.67% (30/45) in the control group, and there was no statistically significant difference ( χ2=0.87, P=0.352) . Conclusion:Cetuximab combined with mFOLFOX6 chemotherapy regimen in the treatment of advanced colorectal cancer patients has significant clinical efficacy, can improve the immune function of patients, alleviate clinical symptoms, regulate the level of serum tumor markers in patients without increasing adverse reactions, and has good safety.

Osteoporosis is a common disease of old age that affects millions of people worldwide. Besides, it has been a chronic disease difficult to treat in the elderly, so it is of great significance to develop new drugs for the treatment of senile osteoporosis. The endocannabinoid system contains cannabinoid ligands, endocannabinoid receptors, and enzymes required for the synthesis and degradation of endocannabinoids, which play an important role in bone metabolism. Preclinical studies using endocannabinoid system-based therapies in animal models and in vitro have shown that endocannabinoid systems can prevent senile osteoporosis and highlight their therapeutic potential for senile osteoporosis. In this paper, PubMed, ScienceDirect, CNKY, and Wanfang databases were searched for articles related to the endocannabinoid system and osteoporosis. This paper analyzed the pathogenesis of senile osteoporosis (such as calcium, active vitamin D3 deficiency or insufficiency, sex hormone deficiency, cell function decline and secondary to chronic diseases, etc.), and reviewed the various components of the endocannabinoid system and their application in osteoporosis by regulating bone homeostasis in recent years, providing a new direction for the clinical treatment of senile osteoporosis.

Objective:To investigate the impact of sarcopenia on mortality in maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. MHD patients admitted to the blood purification center of Guangzhou Red Cross Hospital in March 2021 were recruited. Demographic data and laboratory indicators, grip strength, and bioelectrical impedance analysis indexes were collected. The patients were divided into sarcopenia group and non-sarcopenia group based on whether they had sarcopenia or not. By following up for 18 months, the survival status of the patients was documented. Kaplan-Meier method, multivariate Cox regression model, and Fine-Gray competing risk model were used to assess the relationship between sarcopenia and all-cause mortality, cardio-cerebrovascular disease mortality, and infection-related disease mortality.Results:A total of 143 MHD patients were enrolled in this study, with age of 65 (58,74) years old and 89 males (62.24%). The prevalence of sarcopenia was 25.17% (36/143). The sarcopenia group had older age ( Z=3.486, P<0.001), higher single-pool Kt/V ( Z=3.634, P<0.001), interleukin-6 ( Z=3.434, P<0.001) and extracellular water/intracellular water ratio ( Z=2.477, P=0.013), and lower body mass index ( Z=-3.210, P=0.001), serum phosphorus ( t=2.475, P=0.015), serum creatinine ( t=3.319, P=0.001), serum albumin ( t=2.851, P=0.005), serum prealbumin ( t=3.384, P<0.001), extracellular water ( Z=-5.124, P<0.001), intracellular water ( Z=-5.417, P<0.001), grip strength ( Z=-3.796, P<0.001) and appendicular skeletal muscle mass index ( t=3.862, P<0.001) than those in the non-sarcopenia group. Kaplan-Meier survival curves showed that the overall survival rate in the sarcopenia group was lower than that in the non-sarcopenia group (Log-rank test χ2=15.99, P<0.001). Multivariable Cox regression analysis demonstrated that sarcopenia was independently correlated with all-cause mortality in MHD patients after adjusting for confounding factors ( HR=2.75, 95% CI 1.07-7.10, P=0.036). Fine-Gray competing risk model result showed that there was no statistically significant difference in cardio-cerebrovascular disease mortality between sarcopenia group and non-sarcopenia group ( SHR=4.99, 95% CI 0.94-26.85, P=0.069); the risk of infection-related disease mortality in sarcopenia group was 5.76 folds than that in non-sarcopenia group ( SHR=5.76, 95% CI 1.15-28.96, P=0.034). Conclusions:There is prevalent sarcopenia in MHD patients. Moreover, sarcopenia is an independent risk factor of all-cause mortality and infection-related disease mortality in MHD patients.

OBJECTIVE To study the quality difference of different specifications of Citri Grandis Exocarpium from different origins，and to provide reference for the orderly development of Citri Grandis Exocarpium industry. METHODS Different specifications [ Citrus grandis ‘Tomentos’young fruit ，Citrus grandis （L.）Osbeck young fruits ，exocarp] of 93 batches of Citri Grandis Exocarpium medicinal materials （decoction pieces ）from different origins [ Citrus grandis ‘Tomentosa’or Citrus grandis （L.）Osbeck] were taken as samples. The contents of naringin and rhoifolin in samples were determined by HPLC. Through pheatmap parameters of R language ，heatmap was drawn for the contents of naringin and rhoifolin according to origins and specifications （young fruit and exocarp ）. RESULTS Of 93 batches of samples ，the contents of naringin and rhoifolin were 16.52-214.64 and 1.03-10.96 mg/g，respectively. Among different specifications ，the contents of naringin and rhoifolin in the young fruit were the highest （their average contents were 108.96 and 6.30 mg/g respectively ）. Heatmap analysis of R language content showed that the contents of naringin and rhoifolin in Citri Grandis Exocarpium from origin of C. grandis ‘Tomentosa’were generally higher than those from origin of C. grandis （L.）Osbeck. Of different specifications of Citri Grandis Exocarpium from origins，the contents of naringin and rhoifolin were higher in KTP young fruit relatively. CONCLUSIONS The quality of Citri Grandis Exocarpium from origin of C. grandis ‘Tomentosa’with the young fruit as specification is the best.

Objective:To analyze the incidence of malignant tumors and its risk factors in patients on maintenance hemodialysis.Methods:Clinical data of 627 hemodialysis patients in Huadu District People′s Hospital of Guangzhou who met the inclusion criteria and exclusion criteria from January 2015 to December 2020 were retrospectively collected. Clinical characteristic of patients with malignant tumors was summarized. Multivariate logistics regression analysis was performed to explore the related factors of malignant tumors.Results:Among the 627 patients, 19(3.03%) developed malignant tumors. There were 14 males and 5 females with a mean age of (65.7±13.7)years. Their mean dialysis duration was (45.16±38.18)months. Gastrointestinal tumor was the most common tumor type (9/19). Univariate analysis showed that the age of the patients combined with malignant tumors was significantly higher, and the serum prealbumin was significantly lower than those patients without malignant tumors (all P<0.05). Logistic regression analysis showed that age was the independent risk factor of developing cancers after adjusting dialysis age, hemoglobin, albumin and parathyroid hormone ( P<0.05). Conclusions:The incidence of malignant tumor is significantly higher in maintenance hemodialysis patients than that in the general population. Age is the risk independent risk factor. Therefore, we should strengthen the monitoring of elderly hemodialysis patients, discover the disease in time, and take measures to improve the prognosis.