BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Objective To explore the correlation between thyroid hormone (TH) sensitivity and metabolic dysfunction-associated steatotic liver disease (MASLD) in euthyroid patients. Methods The euthyroid patients hospitalized in the Department of Endocrinology at Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were enrolled. All patients were evaluated for free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). The FT3/FT4 ratio, thyroid-stimulating hormone index (TSHI), FT3 feedback quantile index (TFQIFT3), and FT4 feedback quantile index (TFIQFT4) were calculated. Hepatic controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were assessed by FibroScan. Results A total of 4 869 participants were enrolled, 3 485 (71.58%) were diagnosed with MASLD. Compared with non-MASLD group of patients, MASLD group had significantly higher levels of serum FT3 and thyroid sensitivity-related parameters, including FT3/FT4, TSHI, TFQIFT3, and TFIQFT4 (P＜0.05). After multivariate adjustment for potential confounders, serum FT3, FT3/FT4, TFQIFT4, TFQIFT3, and TSHI remained positively correlated with the risk of MASLD (P＜0.05). Further analysis revealed that, after adjustment for confounders, FT3, FT3/FT4, TFQIFT4, TFQIFT3, and TSHI were positively correlated with CAP, and TFQIFT4, TFQIFT3, and TSHI were also positively correlated with LSM (P＜0.05). Conclusions Reduced thyroid hormone sensitivity are independently associated with MASLD. Moreover, higher levels of FT3 and decreased thyroid hormone sensitivity are correlated with the progression of MASLD.

Objective To explore the lung protective effect of pressure controlled ventilation-volume guaranteed(PCV-VG)combined with driving pressure(DP)guided lung protective ventilation strategy in patients undergoing thoracoscopic and laparoscopic radical esophagectomy.Methods 70 patients scheduled for elective thoracoscopic and laparoscopic radical esophagectomy were allocated into two groups using a random number table method:Conventional lung protective ventilation strategy group(group C)and DP guided lung protective ventilation strategy under PCV-VG mode group(group P),35 case in each group.Peak airway pressure(Ppeak),plateau pressure(Pplat),dynamic compliance(Cdyn)and DP were compared between the two groups at 5 minutes after intubation(T1),30 min after pneumoperitoneum established(T2),just prior to one lung ventilation(OLV)(T3),30 min after OLV(T4),60 min after OLV(T5)and 15 min from recovery of two lung ventilation(TLV)(T6).The blood pressure(BP),heart rate(HR),arterial partial pressure of oxygen(PaO2),partial pressure of carbon dioxide in arterial blood(PaCO2)and pH were recorded before anesthesia(T0),T2,T3,T4,T5 and T6 time points.The occurrence of postoperative pulmonary complications(PPCs)also recorded.Results Compared with group C,Ppeak in group P at T1,T2,T4,T5 and T6 time points was significantly decreased,and Cdyn was obviously increased,the differences were statistically significant(P＜0.05).At the T1,T4,T5 and T6 time points,the DP was lower in group P compared to group C,and Pplat at T6 time point was lower than that in group C,the differences were statistically significant(P＜0.05).At the time points of T4 and T5,the PaO2 in group P was higher than that in Group C,and the PaCO2 at T6 time point was also higher than that in group C,the differences were statistically significant(P＜0.05).The comparison of PaCO2 at T0,T2,T3,T4 and T5 time points of the two groups,the difference was not statistically significant(P＞0.05).Comparison of pH between the two groups,the difference was not statistically significant at all time points(P＞0.05).The systolic blood pressure(SBP)of group P was higher than that of group C at the T4 time point,and the diastolic blood pressure(DBP)was lower than that of group C at T6 time point,and the differences were statistically significant(P＜0.05);There were no significant differences in SBP and DBP at T0,T2,T3 and T5 time points,and HR at each time point between the two groups(P＞0.05).There was no statistically significant difference in the occurrence of PPCs within 7 d after operation between the two groups(P＞0.05).Conclusion DP guided lung protective ventilation strategy under PCV-VG mode can improve intraoperative respiratory mechanics,and increase oxygenation during OLV in patients undergoing thoracoscopic and laparoscopic radical esophagectomy,but it does not significantly affect the incidence of PPCs within 7 d after operation.It is worthy clinical significant.

Objective To explore the lung protective effect of pressure controlled ventilation-volume guaranteed(PCV-VG)combined with driving pressure(DP)guided lung protective ventilation strategy in patients undergoing thoracoscopic and laparoscopic radical esophagectomy.Methods 70 patients scheduled for elective thoracoscopic and laparoscopic radical esophagectomy were allocated into two groups using a random number table method:Conventional lung protective ventilation strategy group(group C)and DP guided lung protective ventilation strategy under PCV-VG mode group(group P),35 case in each group.Peak airway pressure(Ppeak),plateau pressure(Pplat),dynamic compliance(Cdyn)and DP were compared between the two groups at 5 minutes after intubation(T1),30 min after pneumoperitoneum established(T2),just prior to one lung ventilation(OLV)(T3),30 min after OLV(T4),60 min after OLV(T5)and 15 min from recovery of two lung ventilation(TLV)(T6).The blood pressure(BP),heart rate(HR),arterial partial pressure of oxygen(PaO2),partial pressure of carbon dioxide in arterial blood(PaCO2)and pH were recorded before anesthesia(T0),T2,T3,T4,T5 and T6 time points.The occurrence of postoperative pulmonary complications(PPCs)also recorded.Results Compared with group C,Ppeak in group P at T1,T2,T4,T5 and T6 time points was significantly decreased,and Cdyn was obviously increased,the differences were statistically significant(P＜0.05).At the T1,T4,T5 and T6 time points,the DP was lower in group P compared to group C,and Pplat at T6 time point was lower than that in group C,the differences were statistically significant(P＜0.05).At the time points of T4 and T5,the PaO2 in group P was higher than that in Group C,and the PaCO2 at T6 time point was also higher than that in group C,the differences were statistically significant(P＜0.05).The comparison of PaCO2 at T0,T2,T3,T4 and T5 time points of the two groups,the difference was not statistically significant(P＞0.05).Comparison of pH between the two groups,the difference was not statistically significant at all time points(P＞0.05).The systolic blood pressure(SBP)of group P was higher than that of group C at the T4 time point,and the diastolic blood pressure(DBP)was lower than that of group C at T6 time point,and the differences were statistically significant(P＜0.05);There were no significant differences in SBP and DBP at T0,T2,T3 and T5 time points,and HR at each time point between the two groups(P＞0.05).There was no statistically significant difference in the occurrence of PPCs within 7 d after operation between the two groups(P＞0.05).Conclusion DP guided lung protective ventilation strategy under PCV-VG mode can improve intraoperative respiratory mechanics,and increase oxygenation during OLV in patients undergoing thoracoscopic and laparoscopic radical esophagectomy,but it does not significantly affect the incidence of PPCs within 7 d after operation.It is worthy clinical significant.

OBJECTIVE To study the anti-fatigue effects of differently-cultivated Astragalus extract in a hypoxic environment of the plateau and explore the related mechanisms.METHODS Fifty-six male KM mice were randomly divided into the hypoxic swimming control(HSC)group,imitation wild Astragalus extract(IWA)430,860 and 1 720 mg·kg-1 groups,and cultivated Astragalus extract(CA)463,925 and 1 850 mg·kg-1 groups.The drug was administered by gavage once daily for 15 days,while body mass was monitored every three days.After 15 days of gavage,the mice were subjected to load swimming(5%body weight)in a hypobaric chamber(simulating a 4 000 m altitude),with exhaus-tive swimming time measured to identify the optimal dosage.Following randomization,fifty male KM mice were assigned to five groups:normoxic control(NC),hypoxic control(HC),HSC,IWA 860 and CA 925 mg·kg-1.All groups underwent daily gavage for 15 d before 90 min non-weight-bearing swimming was conducted in the HSC,IWA 860 and CA 925 mg·kg-1 groups within a hypobaric chamber,followed by immediate measurement of muscle strength.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in liver and gastrocnemius muscle tissues.Blood urea nitrogen(BUN),blood glucose(BG)and serum lactic acid(LA),glutathione(GSH),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),superoxide dismutase(SOD),liver glycogen(LG)and muscle glycogen(MG)in livers and muscles,and total antioxidant capacity(T-AOC)and reactive oxygen species(ROS)in muscles were measured by commercial kits.Taurine and hypotaurine were measured by HPLC.Enzyme-linked immunosorbent assay(ELISA)was used for cysteine sulfenic acid decarboxylase(CSAD)measure-ment.Western blotting was used to detect protein expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in skeletal muscles.RESULTS Compared with the HSC group,the swimming time was prolonged in IWA 463,IWA 860,CA 925 and CA 1 850 mg·kg-1 groups.Compared with the HSC group,the muscle strength of mice in the IWA 860 mg·kg-1 group and the CA 925 mg·kg-1 group was significantly increased,histo-pathological damage in the liver and gastrocnemius muscle was reduced,serum levels of LA and BUN were significantly decreased,levels of BG,LG and MG were significantly increased,levels of GSH,GSH-Px and SOD were significantly increased,contents of MDA were significantly decreased,expressions of CSAD were significantly increased in liver tissue,contents of GSH,T-AOC,taurine and hypotaurine were significantly increased,levels of ROS were significantly decreased,and protein expressions of PI3K,Akt,Nrf2,HO-1 were significantly upregulated in muscle tissues.CONCLUSION Under simulated high-altitude hypoxic conditions,extracts of Astragalus membranaceus cultivated by two methods consis-tently exhibit anti-fatigue effects.Its mechanisms may be mitigating oxidative stress,augmenting taurine and hypotaurine metabolic regulation,and activating PI3K/Akt and Nrf2/HO-1 signaling pathways.IWA has a better anti-fatigue effect than CA.

OBJECTIVE To study the anti-fatigue effects of differently-cultivated Astragalus extract in a hypoxic environment of the plateau and explore the related mechanisms.METHODS Fifty-six male KM mice were randomly divided into the hypoxic swimming control(HSC)group,imitation wild Astragalus extract(IWA)430,860 and 1 720 mg·kg-1 groups,and cultivated Astragalus extract(CA)463,925 and 1 850 mg·kg-1 groups.The drug was administered by gavage once daily for 15 days,while body mass was monitored every three days.After 15 days of gavage,the mice were subjected to load swimming(5%body weight)in a hypobaric chamber(simulating a 4 000 m altitude),with exhaus-tive swimming time measured to identify the optimal dosage.Following randomization,fifty male KM mice were assigned to five groups:normoxic control(NC),hypoxic control(HC),HSC,IWA 860 and CA 925 mg·kg-1.All groups underwent daily gavage for 15 d before 90 min non-weight-bearing swimming was conducted in the HSC,IWA 860 and CA 925 mg·kg-1 groups within a hypobaric chamber,followed by immediate measurement of muscle strength.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in liver and gastrocnemius muscle tissues.Blood urea nitrogen(BUN),blood glucose(BG)and serum lactic acid(LA),glutathione(GSH),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),superoxide dismutase(SOD),liver glycogen(LG)and muscle glycogen(MG)in livers and muscles,and total antioxidant capacity(T-AOC)and reactive oxygen species(ROS)in muscles were measured by commercial kits.Taurine and hypotaurine were measured by HPLC.Enzyme-linked immunosorbent assay(ELISA)was used for cysteine sulfenic acid decarboxylase(CSAD)measure-ment.Western blotting was used to detect protein expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),nuclear factor E2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in skeletal muscles.RESULTS Compared with the HSC group,the swimming time was prolonged in IWA 463,IWA 860,CA 925 and CA 1 850 mg·kg-1 groups.Compared with the HSC group,the muscle strength of mice in the IWA 860 mg·kg-1 group and the CA 925 mg·kg-1 group was significantly increased,histo-pathological damage in the liver and gastrocnemius muscle was reduced,serum levels of LA and BUN were significantly decreased,levels of BG,LG and MG were significantly increased,levels of GSH,GSH-Px and SOD were significantly increased,contents of MDA were significantly decreased,expressions of CSAD were significantly increased in liver tissue,contents of GSH,T-AOC,taurine and hypotaurine were significantly increased,levels of ROS were significantly decreased,and protein expressions of PI3K,Akt,Nrf2,HO-1 were significantly upregulated in muscle tissues.CONCLUSION Under simulated high-altitude hypoxic conditions,extracts of Astragalus membranaceus cultivated by two methods consis-tently exhibit anti-fatigue effects.Its mechanisms may be mitigating oxidative stress,augmenting taurine and hypotaurine metabolic regulation,and activating PI3K/Akt and Nrf2/HO-1 signaling pathways.IWA has a better anti-fatigue effect than CA.

Objective to establish a combined diagnosis model of scleroderma related genes based on gene expression comprehensive database(GEO)and artificial neural network(ANN)and to evaluate its effect and to predict and analyze targeted traditional Chinese medicine.Methods two scleroderma chips GSE23741 and GSE95065 were obtained from the GEO database as the training group data set.Random forest and lasso regression algorithms were used to screen the key genes of scleroderma and construct the ANN model for the diagnosis of scleroderma.The validation data sets GSE76807,GSE32413 and GSE59785 were used to verify the model,and the area under curve(AUC)analysis was used to evaluate the clinical application value of ANN model.The relative expression of key gene mRNA was verified by RT-qPCR experiment.The CIBERSORT algorithm was used to estimate the bioinformatics association between scleroderma and the screened biomarkers.Finally,the key genes were used to screen the targeted traditional Chinese medicine.Results A total of 167 differential genes were obtained.Furthermore,the five most relevant key genes(SERPINE2,SFRP4,SUGCT,FBLN5,NRXN2)were screened by machine learning,and the artificial neural network diagnosis model was constructed.The model was used to draw the subject operating characteristic(ROC)curves diagnosed by the training group and the verification group,and the AUC value of the training group was 1.000.The AUC of verification group were 0.770,0.795 and 0.872 respectively.The result of RT-qPCR experiment is consistent with that of machine learning algorithm.Immune cell infiltration analysis showed that the relative content of memory CD4+T cells was significantly increased in scleroderma group,while the relative content of γ δ T cells in normal group was significantly increased.Key genes are associated with macrophage M1,T cells,memory activated CD4+T cells,resting mast cells,CD8+T cells and so on.According to the key genes,12 traditional Chinese medicines were screened.Most of the four qi and five flavors belong to warm,cold,flat,sweet,pungent and bitter,and most of them belong to the meridians of liver,spleen and lung.Conclusion the artificial neural network diagnosis model of key genes of scleroderma is constructed,which can be used in clinical diagnosis of scleroderma,and the potential targeted traditional Chinese medicine for the treatment of scleroderma is predicted,which provides a new perspective for exploring the pathogenesis of scleroderma.

Objective:To analyze and compare the difference of gene expression profiles in normal colon tissues,colon adenoma and carcinoma tissues by RNA sequencing technology,and re-veal the key genes and potential mechanisms in the development from colon adenoma to carcinoma.Methods:RNA sequencing analysis was carried out on normal colon tissues,colon adenomas and carcinoma tissues of the same patient,and differential genes that were significantly expressed in colon cancer and not significantly expressed in adenoma tissues were obtained,and the GO and KEGG function enrichment analysis was performed.Results:There are 4307 differential genes that are significantly expressed in colon cancer and not significantly expressed in adenoma.The GO and KEGG function enrichment analysis of these genes found that they were mainly enriched in bi-ological processes such as biological process regulation,cell process regulation,protein binding and cancer pathway,PI3K Akt signal pathway MAPK signal pathway.Conclusion:There are many genes involved in the development process from colon adenoma to carcinoma.These genes have the potential to become therapeutic targets for colorectal cancer,providing a new direction for fol-low-up research on colorectal cancer.

Objective To explore the effect of Wenyang Huazhuo Tongluo recipe on pulmonary microvascular injury in mice with scleroderma based on mitophagy.Methods Fifty mice were randomly divided into blank control group(0.9％NaCl,by gavage),control group(0.9％NaCl,by gavage),model group,Wenyang Huazhuo Tongluo recipe group(47mg·kg-1·d-1 Wenyang Huazhuo Tongluo recipe by gavage),positive control group(10 mg·kg-1·d-1 KC7F2 dissolved in phosphate buffer solution intraperitoneal injection),continuous administration for 4 weeks.The expression levels of in vitro membrane translocation enzyme 20(TOMM20),hypoxia inducible factor-1α(HIF-1α),B cell lymphoma-2/adenovirus E1B-19 kDa interacting protein 3(BNIP3),PTEN inducible muscle enzyme protein 1(PINK1)and E3 ubiquitin ligase(Parkin)in lung tissue were detected by immunohistochemistry(IHC).Western blot(WB)was used to detect the expression levels of mitophagy-related proteins(TOMM20,LC3B)and HIF-1α/BNIP3/PINK1/Parkin pathway proteins in pulmonary microvascular endothelial cells.Results The relative content of HIF-1α in microvascular endothelial cells of lung tissue in the control group,model group,Wenyang Huazhuo Tongluo recipe group and positive control group were 0.17±0.02,0.98±0.01,0.66±0.03 and 0.48±0.01;the relative content of BNIP3 were 0.40±0.02,0.74±0.01,0.56±0.01 and 0.60±0.02;the relative content of PINK1 were 0.26±0.04,0.88±0.01,0.65±0.02 and 0.67±0.02;the relative contents of Parkin were 0.33±0.02,0.89±0.01,0.65±0.02 and 0.77±0.02;the relative contents of TOMM20 were 1.10±0.02,0.58±0.01,1.02±0.01 and 0.98±0.03;the relative contents of LC3B-Ⅰ/LC3B-Ⅱ were 0.24±0.01,0.80±0.01,0.53±0.02 and 0.70±0.02,respectively.The content of HIF-1α,BNIP3,PINK1,Parkin and LC3B-Ⅰ/LC3B-Ⅱ in model group was higher than those in control group.Wenyang Huazhuo Tongluo recipe can effectively reduce its content.The content of TOMM20 in the model group was lower than that in control group,and Wenyang Huazhuo Tongluo recipe can effectively increase its content.Conclusion Wenyang Huazhuo Tongluo recipe may inhibit mitophagy and improve SSc pulmonary microvascular injury by increasing TOMM20 and inhibiting the protein expression of LC3B and HIF-1α/BNIP3/PINK1/Parkin signaling pathway.