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Objective:To investigate the clinical efficacy and safety of programmed death protein 1 (PD-1) inhibitos combined with Fuzheng Kang'ai Decoction in patients with stage Ⅲ or Ⅳ non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis in real world.Methods:Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), total survival time (OS) and adverse events of patients with advanced or metastatic NSCLC who received PD-1 inhibitors for the first time in the Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine from August 2018 to March 2021 were retrospectively analyzed, and was prospectively followed up until September 2022. Kaplan-Meier method was used to plot survival curves and evaluate median PFS and median OS, while Cox proportional hazards regression model was used for multivariate analysis.Results:The final 66 patients were included in the study, with an ORR of 33.3% (22/66), a DCR of 86.4% (57/66), a median PFS of 9.90 months, and a median OS of 31.83 months. Univariate analysis showed that median PFS was associated with TNM stage, liver metastasis, PD-L1 expression level, lung immune prognostic index (LIPI), and traditional Chinese medicine syndrome types ( P values were 0.004, 0.033, 0.040, 0.004, and 0.001, respectively). Multivariate Cox regression analysis showed that TNM stage [ HR (95% CI)=4.179 (1.781, 9.804)], PD-L1 expression level 1%-49% [ HR (95% CI)=0.346 (0.127, 0.940)] or ≥ 50% [ HR (95% CI)=0.074 (0.019, 0.288)], LIPI [ HR (95% CI)=14.515 (2.939, 71.681)], and TCM characteristics of deficiency of yang qi [ HR (95% CI)=5.954 (2.093, 16.940)] were independent influencing factors for PFS. The overall and grade 3-5 treatment-related adverse events were 68.2% (45/66) and 9.1% (6/66), respectively. Conclusions:Fuzheng Kang'ai Decoction combined with PD-1 inhibitors is an effective and tolerable therapy for patients with advanced or metastatic NSCLC. TNM stage, liver metastasis, PD-L1 expression, LIPI and TCM characteristics are early predictors of clinical efficacy for patients with stage Ⅲ/Ⅳ NSCLC that receive traditional Chinese medicine combined with immunotherapy .
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Rhodotorula toruloides is a non-conventional red yeast that can synthesize various carotenoids and lipids. It can utilize a variety of cost-effective raw materials, tolerate and assimilate toxic inhibitors in lignocellulosic hydrolysate. At present, it is widely investigated for the production of microbial lipids, terpenes, high-value enzymes, sugar alcohols and polyketides. Given its broad industrial application prospects, researchers have carried out multi-dimensional theoretical and technological exploration, including research on genomics, transcriptomics, proteomics and genetic operation platform. Here we review the recent progress in metabolic engineering and natural product synthesis of R. toruloides, and prospect the challenges and possible solutions in the construction of R. toruloides cell factory.
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Édition de gène , Génie métabolique , Rhodotorula/métabolisme , LipidesRÉSUMÉ
In recent years, it has been common for heart disease patients to undergo urological surgery.The requirements for specialized doctors to accurately assess the risk of perioperative heart disease thrombosis are also increasing. In order to conduct multi-disciplinary disease analysis and discussion in a more standardized profile and promote clinical work progress in a safer manner, this article provides a systematic review and summary of the basic characteristics of antithrombotic drugs, the bleeding risks of urological surgery, the risk identification standards for arteriovenous thrombosis, as well as the withdrawal conditions, bridging selection, and restart treatment of perioperative antithrombotic drugs, based on the constantly updated clinical researches and guideline consensuses in recent years.
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OBJECTIVE: To elucidate the potential molecular mechanism by which Fuzheng Kang'ai decoction (, FZKA) inhibits proliferation, migration, and invasion of lung cancer cells. METHODS: Varying FZKA concentrations were used to manage lung cancer cells (A549 and PC9). We employed: cell counting kit-8 (CCK-8) and plate clone for-mation assays to examine the cell viability; flow cytometry (FCM) to analyze the cycle arrest; transwell and wound-healing assays to assess the cell invasion and migration, respectively. Further, a quantitative real-time polymerase chain reaction (qRT-PCR) assay was adopted to evaluate the miR-21-5p expression. For protein expression analysis, we employed the Western blot technique. Recombinant miR-21-5p overexpression adenovirus vector harboring GFP was constructed and transfected into A549 and PC9, after which we explored the effect of FZKA on miR-21-5p overexpression. RESULTS: Notably, treatment with FZKA inhibited viability, clone-formation ability, invasion, and migration of lung cancer cells. Mechanistically, FZKA markedly suppressed miR-21-5p expression but elevated the human phosphatase and tensin homology deleted on chromosome ten (PTEN) protein level in both A549 and PC9 cells. Over-expression of miR-21-5p lowered PTEN protein expression. Besides, overexpressed miR-21-5p levels with adenovirus antagonized FZKA-upregulated PTEN protein expression. CONCLUSION: The present study demonstrates how FZKA modulates cell biological behaviors, for instance, it impedes the proliferation by upregulating PTEN expression with miR-21-5p as the target. These findings unveil the potential novel molecular mechanisms from the microRNA aspect by which FZKA suppresses the growth of human lung cancer cells.
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Tumeurs du poumon , microARN , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire , Chromosomes/métabolisme , Régulation de l'expression des gènes tumoraux , Humains , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/métabolisme , microARN/génétique , microARN/métabolisme , Phosphohydrolase PTEN/génétique , Phosphohydrolase PTEN/métabolisme , Tensines/génétique , Tensines/métabolismeRÉSUMÉ
Objective@#To evaluate whether hemodialysis before percutaneous renal biopsy (PRB) reduces the risk of bleeding complications in patients with acute kidney injury (AKI).@*Methods@#This study was a cohort observational study. Patients who were diagnosed as AKI and received PRB in Nanfang Hospital of Southern Medical University from January 2015 to December 2018 were included in the study. Patients were divided into preoperative dialysis group and preoperative non-dialysis group according to whether PRB patients received hemodialysis treatment. According to whether perirenal hematoma occurred after the operation, the patients were divided into the groups with and without the perirenal hematoma. The baseline clinical data of AKI stage, hemoglobin, coagulation function and renal pathological changes before PRB, and perirenal hemorrhage complications after operation, including the size of perirenal hematoma within 24 hours, gross hematuria, low back pain, decreased hemoglobin value and interventional treatment (such as interventional surgery, blood transfusion, etc) in the two groups were compared. The logistic regression model was used to analyze the risk factors of perirenal hematoma after PRB.@*Results@#Ninety patients with AKI were enrolled in this study, including 41 in the preoperative dialysis group and 49 in the preoperative non-dialysis group. The proportion of patients AKI with stage 2-3 in the preoperative dialysis group was significantly higher than that in preoperative non-dialysis group (100.0% vs 75.5%, P<0.001). There were no significant differences in coagulation function indexes and platelet counts between the two groups. Renal ultrasound within 24 hours after PRB showed that there were no significant differences in the incidence of postoperative perirenal hematoma (56.1% vs 63.3%, P=0.489), the incidence of postoperative perirenal large size hematoma (≥5 cm, 26.1% vs 22.6%, P=0.766), and the magnitude of the decrease in hemoglobin (3.7% vs 1.2%, P=0.505) between the preoperative dialysis group and the preoperative non-dialysis group. No blood transfusion, arteriovenous fistula, renal vascular intervention or surgery, and no hospital death occurred in the two groups. The renal pathological manifestations of the patients with and without perirenal hematoma were mainly acute tubular necrosis (ATN) and there were no significant differences between the patients with and without perirenal hematoma in indicators such as age, gender, body mass index, diabetes percentage, hypertension percentage, AKI staging, preoperative dialysis or not, serum creatinine, blood urea nitrogen, hemoglobin, platelet count and renal pathological types. After adjusting for indicators such as preoperative AKI stage and renal pathological changes, logistic regression analysis results showed that perirenal after PRB was not independently correlated with preoperative dialysis (β=0.568, P=0.241); Multivariate logistic regression analysis resluts showed that hematoma (≥5 cm) after PRB was also not independently correlated with preoperative dialysis (β=0.967, P=0.958).@*Conclusions@#Preoperative hemodialysis does not reduce the risk of bleeding complications after PRB in patients with AKI. The role of preoperative hemodialysis in reducing the risk of bleeding complications after PRB needs further study and verification.
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Objective To evaluate whether hemodialysis before percutaneous renal biopsy (PRB) reduces the risk of bleeding complications in patients with acute kidney injury (AKI).Methods This study was a cohort observational study.Patients who were diagnosed as AKI and received PRB in Nanfang Hospital of Southern Medical University from January 2015 to December 2018 were included in the study.Patients were divided into preoperative dialysis group and preoperative non-dialysis group according to whether PRB patients received hemodialysis treatment.According to whether perirenal hematoma occurred after the operation,the patients were divided into the groups with and without the perirenal hematoma.The baseline clinical data of AKI stage,hemoglobin,coagulation function and renal pathological changes before PRB,and perirenal hemorrhage complications after operation,including the size of perirenal hematoma within 24 hours,gross hematuria,low back pain,decreased hemoglobin value and interventional treatment (such as interventional surgery,blood transfusion,etc) in the two groups were compared.The logistic regression model was used to analyze the risk factors of perirenal hematoma after PRB.Results Ninety patients with AKI were enrolled in this study,including 41 in the preoperative dialysis group and 49 in the preoperative non-dialysis group.The proportion of patients AKI with stage 2-3 in the preoperative dialysis group was significantly higher than that in preoperative non-dialysis group (100.0% vs 75.5%,P<0.001).There were no significant differences in coagulation function indexes and platelet counts between the two groups.Renal ultrasound within 24 hours after PRB showed that there were no significant differences in the incidence of postoperative perirenal hematoma (56.1% vs 63.3%,P=0.489),the incidence of postoperative perirenal large size hematoma (≥5 cm,26.1% vs 22.6%,P=0.766),and the magnitude of the decrease in hemoglobin (3.7% vs 1.2%,P=0.505) between the preoperative dialysis group and the preoperative nondialysis group.No blood transfusion,arteriovenous fistula,renal vascular intervention or surgery,and no hospital death occurred in the two groups.The renal pathological manifestations of the patients with and without perirenal hematoma were mainly acute tubular necrosis (ATN) and there were no significant differences between the patients with and without perirenal hematoma in indicators such as age,gender,body mass index,diabetes percentage,hypertension percentage,AKI staging,preoperative dialysis or not,serum creatinine,blood urea nitrogen,hemoglobin,platelet count and renal pathological types.After adjusting for indicators such as preoperative AKI stage and renal pathological changes,logistic regression analysis results showed that perirenal after PRB was not independently correlated with preoperative dialysis (β=0.568,P=0.241);Multivariate logistic regression analysis resluts showed that hematoma (≥5 cm) after PRB was also not independently correlated with preoperative dialysis (β=0.967,P=0.958).Conclusions Preoperative hemodialysis does not reduce the risk of bleeding complications after PRB in patients with AKI.The role of preoperative hemodialysis in reducing the risk of bleeding complications after PRB needs further study and verification.
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Objective:To prospectively investigate the characteristics of acute kidney injury (AKI) that progressed to chronic kidney disease (CKD) (AKI to CKD) in patients hospitalized for AKI, determine the risk factors of AKI to CKD, and preliminarily evaluate the performance of clinical risk factor model for predicting AKI to CKD.Methods:This was a prospective, observational cohort study. Patients hospitalized for AKI and without a prior CKD [estimated glomerular filtration rate (eGFR)<60 ml·min -1·(1.73 m 2) -1] were enrolled in Nanfang Hospital of Southern Medical University from April 2015 to December 2019. Survived patients were followed 90 days after AKI and the renal function 90 days post AKI was determined. The primary endpoint was AKI to CKD, defined as new-onset CKD [eGFR<60 ml·min -1·(1.73 m 2) -1 90 days post AKI]. According to AKI progressed to CKD or not, AKI patients were divided into two groups (with or without AKI to CKD). The baseline clinical data of demographics, comorbidities, baseline renal function, AKI severity, receiving hemodialysis or not, and other lab parameters were compared between two groups. The logistic regression model was used to analyze the risk factors of AKI to CKD. Finally, receiver operator characteristic (ROC) curve was drawn to evaluate the performance of clinical risk factor model for predicting AKI to CKD. Results:A total of 168 patients with AKI was enrolled in this study[male, n=91; female, n=77; age (44.0±18.4) years], in which 64 patients (38.1%) developed new-onset CKD 90 days post AKI and 104 patients (61.9%) did not. Compared to those without AKI to CKD, patients with AKI to CKD were older, and had a higher proportion of hypertension, lower levels of eGFR and hemoglobin, higher proportion of receiving hemodialysis, and higher level of discharged serum creatinine (all P<0.05). There was no significant difference in the proportion of diabetes and use of RAS inhibitors, urine protein level, and other lab parameters between two groups. Multivariate logistic regression analysis shows that receiving hemodialysis ( OR=2.516, 95% CI 1.251-5.060, P=0.010), hypertension ( OR=2.446, 95% CI 1.124-5.324, P=0.024), and lower baseline eGFR ( OR=0.975, 95% CI 0.950-0.999, P=0.043) were the independent risk factors for AKI to CKD. The clinical risk factor model including age, receiving hemodialysis, hypertension, and baseline eGFR produced moderate performance for predicting AKI to CKD, with the area under ROC curve of 0.712, 95% CI 0.634-0.790. Conclusions:AKI survivors are at high risk for developing CKD. Receiving hemodialysis, hypertension, and lower baseline eGFR are independent risk factors for predicting AKI to CKD. More studies are needed to improve the performance of clinical risk factor model for early detecting high risk patients who will develop AKI to CKD.
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Objective To explore the relation between rheumatoid arthritis (RA) and the meteorological factors.Methods All RA cases in the group were followed for 12 months,patients were follow-up for every two weeks.In each followed-up,all RA cases were evaluated by the disease activity score-28 (DAS28) and the improved Jamieson questionnaire,and the correlation of the DAS28 and the average values of meteorolo-gical factors (temperature,humidity,atmospheric pressure,relative humidity,wind speed) by Pearson correlation coefficient.The moderate-severe activity cases were evaluated by chi-square test of different seasons.Results One hundred and eighty-eight cases completed the observation,One hundred and sixty-four cases were in moderate disease activities (x2=9.42,P=0.022).Sixty-eight cases were distributed in winter,which was significantly higher than other three seasons.The average temperature and wind speed was negatively related to the DAS28 (r=-0.743,P<0.01; r=-0.576,P=0.003).Conclusion The activity of RA has the characteristics of seasonal changes,and is easily being aggravated in winter.Many factors may influence RA,including temperature and wind speed.Creating an appropriate micro-climate environment is beneficial for RA patients to reduce the disease activity.
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<p><b>OBJECTIVE</b>To evaluate the association between central pulse pressure level and cardiovascular diseases (CVD) in patients receiving maintenance peritoneal dialysis.</p><p><b>METHODS</b>This cross-sectional study was conducted in 234 patients on maintenance peritoneal dialysis. Central pulse pressure levels were measured using a SphygmoCor analyzer, and cardiovascular diseases were defined as diagnosed ischemic heart disease, heart failure, stroke or peripheral vascular disease.</p><p><b>RESULTS</b>The central pulse pressure levels of patients with CVD were significantly higher than those without CVD (51.7 ± 22.5 vs 43.7 ± 17.8 mmHg, P=0.004), while the brachial pulse pressure levels were comparable between the two patient groups. After adjusting for brachial pulse pressure and other relevant risk factors, central pulse pressure level was found to independently associate with CVD (adjusted OR=1.33, 95% CI 1.01-1.73, P=0.04 ).</p><p><b>CONCLUSION</b>High central pulse pressure level may serve as a risk factor for CVD in patients on maintenance peritoneal dialysis.</p>
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Humains , Pression sanguine , Maladies cardiovasculaires , Études transversales , Dialyse péritonéale , Facteurs de risqueRÉSUMÉ
Cell growth profiles were evaluated in shake-flask culture to improve sclareol production by the engineered yeast strain Saccharomyces cerevisiae S7. Product formation was tightly coupled with cell growth. High cell density cultures were performed with different carbon sources using a dissolved oxygen level feedback-control strategy in a 3 L bioreactor. The titers of sclareol were 253 mg/L, 386 mg/L and 408 mg/L, respectively, when glucose, ethanol and glucose/ethanol mixture were used as the carbons sources. The maximal titer was 27-fold higher than that obtained under shake-flask culture conditions. The results suggested that the presence of ethanol was beneficial to sclareol production. These results provided useful information for optimization of yeast cell factory and efficient production of terpenoids.
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Bioréacteurs , Milieux de culture , Diterpènes , Métabolisme , Éthanol , Glucose , Microbiologie industrielle , Méthodes , Oxygène , Saccharomyces cerevisiae , MétabolismeRÉSUMÉ
Objective To investigate the therapeutic efficacy of Chinese medicine of Wusheng Tincture for external application in treating cancer pain, and to observe its effect on the quality of life ( QOL) of cancer patients. Methods Eighty-three cancer pain patients were randomized into treatment group (N=42) and control group (N=41). Except 5 cases dropping out for the itch of skin, a total of 78 cases finished the treatment, 40 in the treatment and 38 in the control group. The patients were given the corresponding medicine according to the classification of numerical rating scale ( NRS) scores. In the control group, the patients were treated following the three-step analgestic ladder issued by World Health Organization ( WHO). The treatment group was given external application of Wusheng Tincture on the painful regions based on the same three-step analgestie ladder treatment as that of the control group, the treatment course lasting 7 days. The rating scale NRS scores and QOL scores were observed for the assessment of therapeutic effect and QOL of the two groups. Results (1) On medication day 7, NRS scores in both groups were decreased as compared with those one day before treatment (P0.05) . (2) The total effective rate of the treatment group was 82.5%, and that of the control group was 68.4%, the difference being significant between the two groups ( P0.05) . ( 3) On medication day 7, QOL scores were much lower in both groups than those one day before medication, the difference being significant ( P0.05) . Conclusion External application of Wusheng Tincture may have certain therapeutic effect in treating patients with mild cancer pain, but fails in enhancing the effect for patients with moderate and severe pain, either in improving the QOL of cancer pain patients when used together with WHO three-step analgestic ladder.
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To evaluate the effectiveness of enzymatic assisted extraction (EAE) of lipid from the oleaginous yeast Rhodosporidium toruloides in the presence of beta-1,3-glucomannanase at a larger scale, we investigated the effects of enzymatic treatment and extraction conditions on lipid extraction yields at 10-L scale by using the broth of R. toruloides Y4 as the feed and ethyl acetate as the solvent. When it was treated for 0.5 h, the lipid extraction yield reached 71.1%, indicating that the enzymatic treatment process reached similar efficiency to that obtained at 10-mL scale. The inhibitory effect of emulsification was greatly reduced by repeated extraction. After extracted for three times, yields of lipid extraction, solvent recovery and total material recovery reached 92.9%, 87.0% and 94.2% respectively. As it can use the lipid production slurry with good extraction efficiency, EAE technology is promising for industrial production of microbial lipids.
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Basidiomycota , Métabolisme , Biocarburants , Bioréacteurs , Fermentation , Microbiologie industrielle , Lipides , beta-Mannosidase , MétabolismeRÉSUMÉ
Objective To investigate the incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers (ARB) alone,or combined with angiotensin-converting enzyme inhibitors (ACEI) in Chinese patients with non-diabetic nephropathy.Methods A total of 144 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB for a mean follow-up period of 12 months.Aldosterone breakthrough was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment.Results In 6 months,aldosterone breakthrough occurred in 21 patients,corresponding to 14.58%,while in 12 months,occurred in 39 patients,corresponding to 27.08%.Although the overall urinary protein excretion (UPE) decreased after treatment in both groups (P<0.05),non-breakthrough group had a more remarkable reduction in UPE (P<0.05).Univariate Logistic regression demonstrated that risk factors of aldosterone breakthrough included pre-treatment values of UPE (OR=3.643,P=0.073) and eGFR (OR=0.980,P=0.025).Multivariate Logistic model revealed pre-treatment values of eGFR was positively associated with aldosterone breakthrough (OR=0.980,P=0.025).Conclusions The incidence of the aldosterone breakthrough increases with duration of treatment.The patients with aldosterone breathrough have higher level of UPE,and enhanced decline in eGFR.Pretreatment value of eGFR is independent risk factor of aldosterone breakthrough.
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Objective To determine the association between asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, with atherosclerosis in patients with chronic kidney disease (CKD). Methods One hundred thirty-eight CKD patients were enrolled in this study. Serum levels of L-arginine, ADMA, and SDMA were measured by high-performance liquid chromatography (HPLC). Common carotid arteries intimae-medial thickness (CCA-IMT) ,cross-sectional calculated intimae-medial thickness(cIM area)and atherosclerotic plaque were detected by noninvasive high-resolution B-mode ultrasonography. Results Serum levels of ADMA and SDMA were significantly increased in CKD patients (n=138) compared with age matched healthy subjects (n=42,P<0.01). ADMA and SDMA levels increased with the progression of renal dysfunction and were negatively related to creatinine clearance (Ccr) in pre-dialysis patients (r=-0.315,P<0.05;r=-0.426,P<0.01). Serum levels of ADMA and SDMA in dialysis patients (n=74)were significantly higher than those in pre-dialysis patients (P<0.05). Patients with carotid artery plaques showed significantly higher levels of ADMA compared with those without plaques. Serum levels of ADMA closely correlated with the mean IMT (r=0.471, P<0.01) and cIM area value (r=0.430, P<0.01). These correlations remained significant even after adjusting GFR,age,gender ,and other risk factors for atherosclerosis in the multiple regression analysis. Conclusion Serum levels of ADMA increased with the progression of CKD and may play a role in the pathogenesis of accelerated atherosclerosis in CKD patients.
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In order to improve nursing students’coping-styles and self-confidence and help them to acclimate the needs of the future community,we trained their copingstyles and selfconfidence throughthe physique training and the cognitive restructing ,and gained good effect.
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@#Peak Torque(PT),Total Work(TW),Average Power(AP),Torque Acceleration Energy(TAE),Set Total Work(STW),Endurance Ratio (ER)and DOrsal/plantar ratio of ankle dorsal and plantarflexion were tested in 101 patients with lumbar disc protrusion using a Cybex一6000 isokinetic muscle test-ing instrument.The results showed the most tested of the affected side was signficantly lower than that onthe opposite side. The PT,TW and STW of the affected side was lower 70一80%than that on the oppo-site side. The rest was lower 20一30%than another side. No significant difference of endurance ratios be-tween the affected and unaffected sides was noted.
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Objective To investigate the antioxidative and antiaging effects of the bioactive extract from Agrocybe aegerita. Method Fruit flies and D-galactose induced aging mice were fed with the bioactive extract from Agrocybe aegerita. The lifespan of fruit fly and spleen index, brain index,SOD activity in serum and lipofuscin level in 1iver of the mice were measured, and its acute toxic effect was studied. Results The bioactive extract from Agrocybe aegerita could significantly increase the mean lifespan and half death time of fruit flies. The percentage of life prolongation was 41.81% compared with the control. Compared to the models, SOD activity in serum,spleen index and brain index of male mice fed with 800mg/(kg.d) of the bioactive extract from Agrocybe aegerita were respectively increased by 42.36%, 33.33% and 17.85%,while lipofuscin content of liver decreased by 50.06%. 20g/(kg.d) of the bioactive extract from Agrocybe aegerita was safe for mouse. Conclusion The bioactive extract from Agrocybe aegerita have obviously antioxidative and antiaging effects with little side effect.