Chinese Medicine Intervention in Signaling Pathways Related to Diabetic Ulcer： A Review / 中国实验方剂学杂志

Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E2-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.

Role and mechanism of noncoding RNA in diabetic peripheral neuropathy / 中国组织工程研究

BACKGROUND:Persistent hyperglycemia has been identified as promoting neurovascular dysfunction,leading to irreversible endothelial dysfunction,increased neuronal apoptosis,oxidative stress and inflammation.These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy.Noncoding RNAs may provide a new strategy for understanding the etiology,pathogenesis and treatment of the disease. OBJECTIVE:To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad,in order to provide new ideas and approaches for noncoding RNAs in the prevention,diagnosis and treatment of diabetes neuropathy. METHODS:CNKI and PubMed were retrieved for relevant literature published from database inception to 2022.The key words were"noncoding RNA;lncRNA;miRNA;diabetes peripheral neuropathy;expression profile"in Chinese and English,respectively.The retrieved documents were summarized and analyzed,and 61 articles were finally selected for further review. RESULTS AND CONCLUSION:(1)Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy.Among the most widely studied regulatory noncoding RNA species,there are long noncoding RNAs,circular RNAs and microRNAs.(2)Through the regulation of noncoding RNAs,the activation or inhibition of related cell pathways,inflammatory genes and downstream-related cytokines will inhibit cell apoptosis,improve inflammation,and thus change the expression of target genes to participate in the process of diabetic neuralgia.(3)Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy,the mechanisms of many noncoding RNAs are unclear,and the same noncoding RNAs may play different roles in different modes.Therefore,it is necessary to further study their action modes in disease etiology and pathology,thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy.However,the criteria for evaluating noncoding RNA activity have not yet been established,and further research is needed on which specific noncoding RNAs play a dominant regulatory role.(4)MicroRNAs,long noncoding RNAs and their target genes can regulate progressive neuropathy,which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy.

Effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway / 西安交通大学学报(医学版)

【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.

Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR / 中华心血管病杂志

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

Research progress on the histological scoring system for nonalcoholic fatty liver disease / 中华肝脏病杂志

Non-alcoholic fatty liver disease (NAFLD) has replaced chronic hepatitis B as the most common chronic liver disease in China and has now been renamed metabolic dysfunction-associated fatty liver disease (MAFLD). The Brunt, the American NASH Clinical Research Network (NASH-CRN), the European Steatosis, Activity, and Fibrosis/Fatty Liver Inhibition of Progression (SAF/FLIP), and the Pediatric NAFLD are currently the four semi-quantitative grading systems for histological evaluation. This paper reviews these four scoring systems for the clinical selection of appropriate systems for diagnosis and prognosis assessment. This article is a review, and in order to coordinate the evaluation criteria of various scoring systems, the old name "NAFLD" is used.

Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Chinese Medicine Intervenes in NLRP3 Inflammasome in Treatment of Bone and Joint Diseases： A Review / 中国实验方剂学杂志

The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.

Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique / 中华心血管病杂志

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

Study on the value of fragmented red blood cell and fragmented red blood cells percentage for predicting the prognosis of sepsis patients / 中华预防医学杂志

To explore the predictive efficacy of fragmented red blood cells (FRC) and fragmented red blood cells percentage(FRC%) with regarding for the prognosis of septic patients, along with comparing with routine coagulation parameters. A prospective study was conducted. A total of 101 patients with sepsis who met the requirements admitted to the Intensive Care Department of the Third Xiangya Hospital of Central South University from June 1, 2022 to January 10, 2023 were selected as the research objects, they were divided into survival group and death group according to the 30-day prognosis. The clinical data and laboratory indexes such as FRCs, FRC% and Platelet (PLT) were compared between the survival group and the death group. Univariate logistic regression analysis was used first, then multivariate logistic regression analysis was used to analyze the factors affecting the prognosis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each parameter in the regression model for the prognosis of sepsis. The results showed that the levels of FRCs, FRC%, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer in death group were significantly higher than those in survival group, and PLT in death group were significantly lower than those in survival group (Z or t values were -3.712,-3.793,-2.119,-2.007,-2.209,all P<0.05). FRCs or FRC% and PLT could be independent predictors of 30-day mortality. The area under the ROC curve (AUC) of PLT for predicting 30-day death in sepsis patients was 0.727 (95%CI 0.629-0.811, P<0.01), when the optimal threshold was 137 ×109/L, the sensitivity was 83.87% and the specificity was 57.14%. The AUC of FRCs for predicting 30-day death in sepsis patients was was 0.732 (95%CI 0.635-0.815, P<0.01), when the optimal threshold was 10.1×109/L, the sensitivity was 77.42%, and the specificity was 67.14%. The AUC of FRC% for predicting 30-day death in sepsis patients was 0.737 (95%CI 0.640-0.820, P<0.01), When the optimal threshold was 0.34%, the sensitivity was 77.42%, and the specificity was 65.71%. In conclusion,PLT, FRCs and FRC% have great application value in the prognosis of sepsis. When the PLT, FRCs and FRC% of sepsis patients are more than 137 ×109/L, 10.1×109/L and 0.34% respectively, it is necessary to take necessary and reasonable clinical intervention measures as soon as possible.

Safety and efficacy of transcatheter aortic valve replacement using the "All in One" single artery/vessel technique / 中华心血管病杂志

Objective: To explore the safety and efficacy of transcatheter aortic valve replacement (TAVR) using the "All in One" single-artery/vessel technique. Methods: This is a retrospective study. A total of 30 consecutive patients underwent TAVR using the single artery/vascular technique in Beijing Anzhen Hospital from August to December 2021 were included. Baseline clinical data, operative situation, postoperative outcomes, and incidence of adverse events during hospitalization and at one month post TAVR were analyzed. Results: Mean age was (72.6±9.7) years, 16 were male patients, STS score was (4.73±3.12)%. Four patients were diagnosed as isolated aortic regurgitation (all with tricuspid aortic valves), and 26 patients were diagnosed as aortic stenosis (AS), 10 of whom with tricuspid aortic valves and 16 of whom with bicuspid aortic valves. The single-vessel technique was applied in 3 aortic stenosis cases; the single-artery technique was applied in 27 cases. Echocardiography was performed immediately after procedure and results showed no or trace perivalvular leak in 27 cases and small perivalvular leak in 3 cases; the mean aortic transvalvular gradient of 26 AS patients decreased from (50.4±16.0) mmHg (1 mmHg=0.133 kPa) to (9.4±3.2) mmHg (P<0.001). The procedure time was (64.8±18.9) min. There were no intraoperative death, valve displacement, conversion to surgery, coronary artery occlusion in all 30 patients. There were no major cardiac adverse events such as myocardial infarction or stroke occurred during hospitalization or at follow-up. One-month follow-up echocardiography indicated prosthesis works well. The symptoms were significantly alleviated, and the Kansas City Cardiomyopathy Score (KCCQ score) of all patients increased from 48.1±18.4 to 73.5±17.6 (P<0.001). Conclusions: TAVR using the single artery/vessel technique is safe and feasible. This technique is related to reduced access complications and worthy of wide application.

Study on the value of fragmented red blood cell and fragmented red blood cells percentage for predicting the prognosis of sepsis patients / 中华预防医学杂志

To explore the predictive efficacy of fragmented red blood cells (FRC) and fragmented red blood cells percentage(FRC%) with regarding for the prognosis of septic patients, along with comparing with routine coagulation parameters. A prospective study was conducted. A total of 101 patients with sepsis who met the requirements admitted to the Intensive Care Department of the Third Xiangya Hospital of Central South University from June 1, 2022 to January 10, 2023 were selected as the research objects, they were divided into survival group and death group according to the 30-day prognosis. The clinical data and laboratory indexes such as FRCs, FRC% and Platelet (PLT) were compared between the survival group and the death group. Univariate logistic regression analysis was used first, then multivariate logistic regression analysis was used to analyze the factors affecting the prognosis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each parameter in the regression model for the prognosis of sepsis. The results showed that the levels of FRCs, FRC%, prothrombin time (PT), activated partial thromboplastin time (APTT) and D-dimer in death group were significantly higher than those in survival group, and PLT in death group were significantly lower than those in survival group (Z or t values were -3.712,-3.793,-2.119,-2.007,-2.209,all P<0.05). FRCs or FRC% and PLT could be independent predictors of 30-day mortality. The area under the ROC curve (AUC) of PLT for predicting 30-day death in sepsis patients was 0.727 (95%CI 0.629-0.811, P<0.01), when the optimal threshold was 137 ×109/L, the sensitivity was 83.87% and the specificity was 57.14%. The AUC of FRCs for predicting 30-day death in sepsis patients was was 0.732 (95%CI 0.635-0.815, P<0.01), when the optimal threshold was 10.1×109/L, the sensitivity was 77.42%, and the specificity was 67.14%. The AUC of FRC% for predicting 30-day death in sepsis patients was 0.737 (95%CI 0.640-0.820, P<0.01), When the optimal threshold was 0.34%, the sensitivity was 77.42%, and the specificity was 65.71%. In conclusion,PLT, FRCs and FRC% have great application value in the prognosis of sepsis. When the PLT, FRCs and FRC% of sepsis patients are more than 137 ×109/L, 10.1×109/L and 0.34% respectively, it is necessary to take necessary and reasonable clinical intervention measures as soon as possible.

Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway / 中国中药杂志

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

Principles and strategies for species identification based on analysis of whole-genome / 药学学报

The main sources of natural drugs include various biological species such as plants, animals, and microorganisms. The accurate identification of these species is the bedrock of natural drug development. We propose a novel method of species identification in this paper: analysis of whole-genome (AGE), a molecular diagnostic method used to identify species by finding species-specific sequences from the whole genome and precisely recognizing the specific target sequences. We elaborate that the principle for species identification based on AGE is that the genome sequences of diverse species must differ and divide the implementation strategy of the method into two levels of research and application. Based on our analysis of its characteristics, the method would have the potential advantages of reliable principle, high specificity, and wide applicability. Moreover, three crucial concerns related to building method systems including genome acquisition, bioinformatics analysis, and database construction, are further discussed. In summary, we offer theoretical underpinnings and methodological guidance for the development of bioinformatics software and commercial kits, indicating AGE has great application potential in objects, subjects, and industries.

Systematic analysis of MYB transcription factors related to the geniposide biosynthesis in Gardenia jasminoides Ellis based on whole genome / 药学学报

MYB transcription factors are involved in the regulation of various secondary metabolites biosynthesis. Gardenia jasminoides Ellis is the commonly used Chinese herbal medicine, and its main active ingredient is geniposide. Here, leaves and flower buds at different developmental stages of G. jasminoides were used to explore MYB transcription factors related to geniposide biosynthesis based on genome and transcriptome analysis. Transcriptome data analysis showed that, different from the expression of the common pathway genes for terpenoid biosynthesis, the expression level of genes in the specific pathway of geniposide biosynthesis was significantly higher in flower buds than in leaves, which was the same as the organ accumulation pattern of this component. And the promoter regions of geraniol synthase, iridoid synthase and geniposidic acid methyltransferase involved in the specific pathway all contained multiple MYB-binding sites. A total of 105 MYB transcription factors were obtained by annotating the coding genes of G. jasminoides, which were divided into 68 1R-MYB, 33 R2R3-MYB, 3 3R-MYB and 1 atypical MYB transcription factor according to the number of conserved domain. Based on the analysis of phylogenetic tree and quantitative real-time PCR, three candidate MYB transcription factors related to geniposide biosynthesis were selected, including potential positive regulation factor GjMYB23 and negative regulation factors GjMYB31 and GjMYB73. The results of this study will lay a foundation for searching the regulation of geniposide biosynthesis and further analysis of the quality formation mechanism of G. jasminoides, so as to promote the breeding of excellent varieties of G. jasminoides.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Single center experience of transcatheter aortic valve replacement with a simplified operative protocol / 中华心血管病杂志

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

Preliminary evaluation on the efficacy of emergency transcatheter aortic valve replacement: a multicenter study / 中华心血管病杂志

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Systematic screening and analysis of bZIP transcription factors in Glycyrrhiza uralensis and their response to ABA stress / 药学学报

Licorice, one of the most commonly used medicinal materials in China, grows mainly in arid and semi-arid regions and has important economic and ecological values. Basic leucine zipper (bZIP) transcription factors in plants play an important role in regulating biological or abiotic stress responses, growth, and secondary metabolite synthesis. bZIP transcription factors in the published whole genome database of Glycyrrhiza uralensis were identified using bZIP sequences found in Arabidopsis thaliana genome as reference, and ABA-dependent bZIP genes were identified by using Illumina high-throughput sequencing. The physical and chemical properties, structure of the encoded proteins, and the gene expression patterns with exogenous ABA stress were analyzed. A total of 69 bZIP transcription factor genes were identified in G. uralensis, named Gubzip1-69, and they were divided into 10 subfamilies (A-I and S) according to their similarity to bZIPs of A. thaliana. By calculating the relative expression levels of the 69 GubZIPs genes under different concentrations of exogenous ABA stress, genes that may be involved in the regulation of ABA signaling pathways were identified, namely GubZIP1, GubZIP5, GubZIP8, GubZIP30, GubZIP33 and GubZIP56. The results of expression pattern analysis of these GubZIPs genes under exogenous ABA stress showed that the expression pattern of GubZIPs genes changed significantly with 50 mg·L-1 ABA. The relative expression levels of these genes decreased 3 h after treatment, and gradually increased 6 h after treatment. Except for GubZIP8, the relative expression levels of these genes were significantly increased after 12 h. Further research on the function of bZIP transcription factors of G. uralensis and elucidating their regulatory mechanisms should be of interest and will provide a scientific basis for cultivating high-quality cultivars of G. uralensis through molecular breeding methods.