Diabetic diarrhea is one of the chronic complications of diabetes, which is particularly closely related to the spleen and kidney. Using these two organs as the theoretical foundation, the root of diabetic diarrhea can be grasped. Pathogenic dampness is responsible throughout the whole process of diabetic diarrhea. Using syndrome differentiation, deficiency is as the basic pattern and excess is the syndrome for diabetic diarrhea; diagnosis and treatment combine symptoms and syndromes, which not only particularly pay attention to protecting the spleen and kidney, but also clearing pathogenic dampness. At the same time, flexible medication is applied according to dynamic symptoms, which can achieve good efficacy.

Objective:To evaluate the value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT-based heterogeneity for early prediction of targeted therapy outcome in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods:From May 2012 to April 2018, 29 patients (all females, median age: 52 (32-69) years) who had HER2 positive metastatic breast cancer and underwent pretreatment 18F-FDG PET/CT in Fudan University Shanghai Cancer Center were retrospectively enrolled. All patients received trastuzumab as first-line treatment and were followed up for 6-87 (median time: 35) months. The relations between clinicopathologic parameters or PET/CT-based parameters and progression-free survival (PFS)/overall survival (OS) were analyzed with Cox univariate analysis. The parameters with P≤0.01 were further analyzed with Cox multivariate analysis. Optimal cut-off values were determined by time-dependent receiver operating characteristic (ROC) curve analysis. The survival analyses were estimated by Kaplan-Meier method and log-rank test. Results:The median OS of the 29 patients was 30 (6-83) months, and the median PFS was 10 (2-29) months. The PET/CT-based heterogeneity index(HI), including the maximum standardized uptake value (SUV max) ratio (SUV max-R; hazard ratio ( HR)=8.6, 95% CI: 2.7-27.8, P<0.001), the mean standardized uptake value (SUV mean)-2.5 (the cut-off value of standardized uptake value (SUV)=2.5) ratio (SUV mean-2.5-R; HR=2.6, 95% CI: 1.2-5.9, P=0.020), the metabolic tumor volume(MTV)-2.5 ratio(MTV-2.5-R; HR=2.4, 95% CI: 1.1-5.2, P=0.030), and the total lesion glycolysis(TLG)-2.5 ratio(TLG-2.5-R; HR=3.2, 95% CI: 1.4-7.4, P=0.008) of the lesion with the highest SUV max to that with the lowest SUV max, were significantly associated with PFS. None of the parameters was significantly associated with OS (all P>0.05). Multivariate analysis showed that the SUV max-R was the only independent predictor for PFS ( HR=6.8, 95% CI: 1.8-26.1, P<0.01). Area under the ROC curve for SUV max-R was 0.747. With a cut-off value of 1.8, SUV max-R could effectively distinguish the benefit from non-benefit population treated with trastuzumab (15.0 vs 7.0 months; χ2=18.68, P<0.01). Conclusion:Pretreatment 18F-FDG PET/CT-based HI has potential value for early prediction of first-line trastuzumab treatment outcome in patients with HER2 positive metastatic breast cancer.

ObjectiveTo investigate the effects of losartan on angiotensin (Ang)Ⅱ-induced the generation of oxidative stress and expression of transforming growth factor β1(TGF-β1) in rat proximal tubular epithelial cells and to explore its underlying mechanism. MethodsNRK-52E cells, a rat proximal tubular epithelial cell line, were applied to explore the antioxidationand antifibrosis of losartan. The expression of three subunits of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, including p47phox, Nox-4, p22phox, and TGF-β1 were determined by real-time RT-PCR and/or Western blot. The generation of reactive oxygen species (ROS) was measured by DCF fluorescence analysis. Superoxide dismutase (SOD) in the supernatant was measured by colorimetric method. Results10-7 mol/L Ang Ⅱ up-regulated p22prox, p47phox and Nox-4 mRNA and protein expression, and the mRNA increased by 5.57-fold, 5.55-fold and 9.41-fold at 24 h (P<0.01, respectively) and the protein increased by 4.53-fold, 4.17-fold and 6.50-fold at 24 h (P<0.01, respectively) as compared with control. Losartan greatly reduced the mRNA elevation of p22prox, p47phox and Nox-4 by 2.71-fold, 2.18-fold and 5.23-fold (P<0.01, respectively) and reduced the protein elevation by 3.20-fold, 2.30-fold and 4.30-fold (P<0.01, respectively) as compared with control. Losartan also inhibited ROS generation induced by Ang Ⅱ in rat proximal tubular epithelial cells. SOD level in the supernatant was markedly decreased after Ang Ⅱ stimulation, while losartan could increase SOD levels (P<0.01). Furthermore, losartan signficantly inhibited Ang Ⅱ-induced TGF-β1 mRNA up-regulation by 64% (P<0.01). ConclusionsLosartan acts as an anti-oxidative and anti-fibrotic agent via the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression.

Objective To evaluate the clinical efficacy of Ningxin decoction in treating patients with permanent atrial fibrillation(AF)of deficiency of both qi and yin type infected by coronavirus disease 2019(COVID-19).Methods From February to August 2023,120 patients with permanent AF of deficiency of both qi and yin type infected by COVID-19 were collected from the outpatient clinic of Guang'anmen Hospital South Campus,China Academy of Chinese Medical Sciences.Patients were randomly divided into a control group and a treatment group using a random number table method,there were 60 cases in each group,and 1 case fell off in each group,leaving 59 cases in each group.The treatment group was given Ningxin decoction(drug composition:Cassia branch 15 g,Cornus officinalis 15 g,Rehmannia 15 g,Rhodiola rosea 15 g,Ginseng 6 g,Mulberry parasitica 10 g,Coptis coptis 3 g,Salvia miltiorrhiza 12 g,Ligusticum chuanxiong 10 g,Ophiopogon 12 g,and schisandra Vinegar 6 g)using formula granules to rinse with water,twice a day.The control group was given 10 mg of coenzyme Q10 twice a day,and both groups were treated continuously for 4 weeks.The improvements in traditional Chinese medicine(TCM)symptoms,including chest pain,dizziness,fatigue,lethargy,palpitations,chest tightness and shortness of breath,insomnia,and excessive dreams before and after treatment in two groups,as well as changes in heart rate variability(HRV)and heart rate deceleration indicators were observed.Results The treatment group showed significant therapeutic effects in improving chest pain,fatigue,palpitations,chest tightness and shortness of breath,there were also improvements in lethargy,insomnia,and excessive dreaming,there was no significant therapeutic effect in improving dizziness.The control group showed significant therapeutic effects in improving palpitations,there were also improvements in chest pain,chest tightness and shortness of breath,while there was no significant therapeutic effect in other aspects.The treatment group showed significantly higher effective rates in improving chest pain,fatigue,lethargy,chest tightness and shortness of breath,insomnia,and excessive dreaming compared to the control group[chest pain:95.45%(42/44)vs.78.57%(33/42),fatigue:83.67%(41/49)vs.31.25%(15/48),lethargy:73.91%(34/46)vs.12.77%(6/47),chest tightness and shortness of breath:88.89%(48/54)vs.63.64%(35/55),insomnia:78.43%(40/51)vs.12.24%(6/49),excessive dreaming:76.09%(35/46)vs.43.75%(21/48),all P<0.05].The standard deviation of all normal to normal RR intervals(SDNN),root mean square of the difference between adjacent NN intervals(RMSSD),standard deviation of all 5-minute RR intervals(SDANN),and percent of NN50 in the total number of NN intervals(PNN50)in both groups after treatment were significantly increased compared to before treatment,and the RMSSD,SDANN,and PNN50 in the treatment group were significantly higher than those in the control group after treatment[RMSSD(ms):28.96±3.59 vs.24.34±2.66,SDANN(ms):108.55±11.80 vs.100.44±13.58,PNN50:7%(6%,7%)vs.5%(5%,6%),all P<0.05].There was no statistically significant difference in heart rate deceleration between the two groups before and after treatment.Conclusion Ningxin decoction has a good effect on the improvement of TCM syndromes and heart rate variability in patients with permanent atrial fibrillation of deficiency of both qi and yin type after being infected by COVID-19.

Objective To explore the possible mechanisms by which fibroblast growth factor(FGF)23 promoted atrial fibrosis in circulation of chronic kidney disease(CKD)by binding to atrial tissue fibroblast growth factor receptor(FGFR)4.Methods Twenty-two healthy male Sprague-Dawley(SD)rats were selected.Rats were randomly selected to undergo 5/6 nephrectomy and fed for 15 weeks to establish a CKD model(n=14).The remaining 8 rats were used as the sham group.The sham group(n=8)underwent the same surgery without removing renal tissue.Body weight,blood pressure,renal function,cardiac ultrasound,epicardial electrocardiography and pathological indices were monitored in both groups.Enzyme-linked immunosorbent assay(ELISA)method was used to determine the circulating levels of FGF23 in the two groups of rats.Transcriptomic analysis of left atrial tissue was performed to search for differentially expressed genes.Rat atrial fibroblasts were divided into the control group,the FGFR inhibitor group,the transforming growth factor-β(TGF-β)group and the TGF-β+FGFR inhibitor group.The expression levels of α-smooth muscle actin(α-SMA),collagenⅠ(Col Ⅰ)and phosphorylated protein kinase B(p-AKT)protein were detected by Western blot assay.Results Systolic blood pressure,blood urea nitrogen and creatinine were elevated in the CKD group of rats.Cardiac electrophysiological study showed that CKD could promote the occurrence of atrial fibrillation(AF)and atrioventricular block.Cardiac ultrasound suggested that the internal diameter of the left atrium was significantly increased in rats of the CKD group.Pathological findings showed that the left atrium in the CKD group underwent significant fibrosis,and epicardial electrical markers showed that left atrial electrical conduction velocity was significantly slower and conduction heterogeneity was significantly increased in the CKD group.These changes were accompanied by higher circulating FGF23.Western blot results showed that FGFR4 expression was upregulated in the CKD group.After blocking the FGF23/FGFR4 signaling pathway in atrial fibroblasts,the fibrosis-related proteins α-SMA,Col Ⅰ and p-AKT/AKT were decreased.Conclusion CKD promotes the occurrence of AF by inducing both structural and electrical remodeling.Increased circulating FGF23 promotes atrial fibrosis by activating the downstream AKT pathway binding to FGFR4 in atrial tissue.