Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Stemona tuberosa alkaloids （STA） on apoptosis and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase （JNK/p38 MAPK） signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups （100， 150， 200， 250， 300 mg⋅L-1）. Thiazole blue （MTT） assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining， flow cytometry， and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2， and the expression of PI3K， phosphorylated （p）-PI3K， Akt， p-Akt， JNK， p-JNK， p38 MAPK， and p-p38 MAPK. ResultCompared with the blank group， STA groups （150， 200， 250， 300 mg⋅L-1） demonstrated the increase in inhibition rate of cell proliferation （P<0.01） and cell clone inhibition rate， and decrease in cell clone formation rate （P<0.01）. In comparison with the blank group， STA groups showed typical characteristics of apoptosis， such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group （P<0.01）. Compared with the blank group， STA （150， 200， 250， 300 mg⋅L-1） significantly up-regulated the protein expression of Caspase-3 and Bax （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 protein （P<0.01）. Compared with the blank group， STA had no significant influence on the total protein expression of PI3K， Akt， JNK， and p38 MAPK. However， STA （150， 200， 250， 300 mg⋅L-1） significantly decreased the levels of p-PI3K and p-Akt （P<0.05， P<0.01） and increased the level of p-p38 MAPK （P<0.05， P<0.01）. Compared with the blank group， STA （200， 250， 300 mg⋅L-1） significantly raised the level of p-JNK （P<0.05， P<0.01）. ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.

Early chest tube removal following single-direction versus conventional uniportal video-assisted thoracoscopic lobectomy: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To explore the feasibility of early chest tube removal following single-direction uniportal video-assisted thoracoscopic surgery (S-UVATS) anatomical lobectomy. Methods    The clinical data of consecutive VATS lobectomy by different surgeons in Xuzhou Central Hospital between May 2019 and February 2022 were retrospectively reviewed. Finally, the data of 1 084 patients were selected for analysis, including 538 males and 546 females, with a mean age of 61.0±10.1 years. These patients were divided into a S-UVATS group with 558 patients and a conventional group (C-UVATS) with 526 patients according to the surgical procedures. The perioperative parameters such as operation time, blood loss were recorded. In addition, we assessed the amount of residual pleural effusion and the probability of secondary thoracentesis when taking 300 mL/d and 450 mL/d as the threshold of chest tube removal. Results    Tumor-negative   surgical margin was achieved without mortality in this cohort. As compared with the C-UVATS group, patients in the S-UVATS group demonstrated significantly shorter operation time (P<0.001), less blood loss (P=0.002), lower rate of conversion to multiple-port VATS or thoracotomy (P=0.003), but more stations and numbers of dissected lymph nodes as well as less suture staplers (P<0.001). Moreover, patients in the S-UVATS demonstrated shorter chest tube duration, less total volume of thoracic drainage and shorter postoperative hospital stay, with statistical differences (P<0.001). After excluding patients of chylothorax and prolonged air leaks>7 d, subgroup analysis was performed. First, assuming that 300 mL/d was the threshold for chest tube removal, as compared with the C-UVATS group, patients in the S-UVATS group would report less residual pleural effusion and less necessitating second thoracentesis with residual pleural effusion>500 mL (P<0.05). Second, assuming that 450 mL/d was the threshold for chest tube removal, as compared with the C-UVATS group, the S-UVATS group would also report less residual pleural effusion and less necessitating second thoracentesis with residual pleural effusion>500 mL (P<0.05). Further multivariable logistic regression analysis indicated that S-UVATS was significantly negatively related to drainage volume>1 000 mL (P<0.05); whereas combined lobectomy, longer operation time, more blood loss and air leakage were independent risk factors correlated with drainage volume>1 000 mL following UVATS lobectomy (P<0.05). Conclusion    The short-term efficacy of S-UVATS lobectomy is significantly better than that of the conventional group, indicating shorter operation time and less chest drainage. However, early chest tube removal with a high threshold of thoracic drainage volume probably increases the risk of secondary thoracentesis due to residual pleural effusion.

Material Basis and Pharmacological Action of Tongxie Yaofang： A Review / 中国实验方剂学杂志

Tongxie Yaofang， also known as Baizhu Shaoyaosan， was first recorded in Danxi's Experiential Therapy （《丹溪心法》） by ZHU Danxi in the Yuan dynasty. It is composed of Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Citri Reticulatae Pericarpium， and Saposhnikoviae Radix， and serves as the representative prescription for the treatment of painful diarrhea. It has the functions of tonifying the spleen， emolliating the liver， relieving pain， and checking diarrhea， and is mainly used in the treatment of gastrointestinal diseases such as irritable bowel syndrome （IBS） and ulcerative colitis （UC）. In addition， it is effective in treating gastrointestinal disorders with mental and psychological abnormalities， as well as obstinate anorexia in children， depression syndrome， and respiratory diseases. Experimental research and clinical practice have shown that Tongxie Yaofang has multi-component， multi-pathway， and multi-target characteristics in the treatment of diseases. The mechanism of Tongxie Yaofang in treating diseases is mainly attributed to anti-inflammation， immune function regulation， intestinal hypersensitivity improvement， emotion regulation， etc. Monoterpene glycosides， flavonoids， chromones， lactones， and other components contained play an important therapeutic role. The research on the systems biology of Tongxie Yaofang， such as metabolomics， proteomics， and network pharmacology， provides a scientific basis for clarifying its mechanism of action and expanding its clinical application. However， there are still some problems to be solved， such as difficulty in combining diseases and syndromes and lack of in-depth systematic research. Through the retrieval and collation of relevant literature， this paper systematically reviewed the material basis， pharmacological effects， and systems biology research of Tongxie Yaofang， aiming to lay a foundation for in-depth research on its mechanism in treating diseases and rational application in clinical practice.

The exercise tolerance and ventilatory efficiency of lung cancer patients with type 2 diabetes / 中华物理医学与康复杂志

Objective:To explore the aerobic exercise tolerance and ventilatory efficiency during cardiopulmonary exercise testing (CPET) of persons with non-small cell lung cancer (NSCLC) complicated by type 2 diabetes mellitus (T2DM).Methods:Forty-eight persons with NSCLC and T2DM formed an NSCLC-T2DM group while another 48 persons with NSCLC but not T2DM formed an NSCLC-non T2DM group. Another 24 healthy counterparts were enrolled into the control group. All completed CPET before pneumonectomies were performed on those with NSCLC. Indexes of static pulmonary function, exercise tolerance, heart rate recovery, ventilation efficiency and gas exchange were computed.Results:Compared with the control group, both NSCLC groups had, on average, lower peak oxygen uptake (VO 2peak), lower anaerobic thresholds (ATs) and lower peak O 2 pulse rates. They also had higher average VE/VCO 2 slopes and VE/VCO 2 nadirs. Compared with the NSCLC-non T2DM group, those with T2DM had a significantly lower average VO 2peak and WRpeak, as well as significantly higher average VE/VCO 2 slope and VE/VCO 2 nadir. Compared with the control group, the average VO 2 and VCO 2 of both NSCLC groups was lower at the AT and during peak exercise, with the NSCLC-T2DM group′s averages significantly lower than those of the NSCLC-non T2DM group during peak exercise. During warm-up and at the AT, the NSCLC groups had a significantly higher average heart rate than the control group. Then, compared with the control group and the NSCLC-non T2DM group, the average heart rate in the NSCLC-T2DM group decreased significantly more slowly during the first three minutes of the recovery period. Compared with the control group, the VE/VCO 2 values of the NSCLC groups were significantly higher at the AT and during peak exercise. During the warm-up and at the AT, the average partial pressures of end-tidal carbon dioxide in the NSCLC groups were significantly lower than among control group, and during peak exercise the NSCLC-T2DM group′s average value was significantly lower than the control group′s. Compared with the control group and the NSCLC-non T2DM group, the NSCLC-T2DM group′s average forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate and maximum voluntary ventilation were all significantly lower. Conclusions:Diabetes impairs the exercise tolerance and ventilation efficiency of persons with NSCLC. Without diabetes their exercise tolerance and ventilation efficiency would be impaired only slightly. CPET can provide a basis for risk assessment before pneumonectomy.

Quantitative evaluation of global left ventricular myocardial work in patients with hepatitis B cirrhosis by pressure-strain loop / 中华肝脏病杂志

Objective: To quantitatively evaluate myocardial work in patients with hepatitis B cirrhosis by using left ventricular pressure-strain loop. Methods: 70 cases with hepatitis B cirrhosis who were hospitalized in Henan Provincial People's Hospital from March to December 2020 were selected as the study group. Patients were divided into three subgroups according to the Child-Pugh score of liver cirrhosis (Child-Pugh class A, B, and C groups: 25, 25, and 20 patients, respectively). At the same time, 25 healthy volunteers were included as the control group. Global longitudinal strain (GLS), global myocardial work index (GWI), global work efficiency (GWE), global constructive work (GCW), and global wasted work (GWW) were obtained by applying pressure-strain loops. The differences were analyzed and compared among the four groups parameters. Results: Compared with the control group, the Child-Pugh class A group had decreased GLS, while Child-Pugh class B and C had decreased GLS, GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Compared with Child-Pugh class A group, Child-Pugh class B group had decreased GLS, GWE, and increased GWW, while Child-Pugh class C group had decreased GLS,GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Compared with Child-Pugh class B group, Child-Pugh class C group had decreased GLS, GWI, GWE, GCW, and increased GWW, and the differences were statistically significant (P<0.05). Conclusion: The pressure-strain loop can detect early myocardial dysfunction, and has a certain value in the diagnosis, treatment and prognosis evaluation of myocardial function changes in patients with hepatitis B cirrhosis.

Vaginal microbiota characteristics and influencing factors in normal pregnant women / 中华微生物学和免疫学杂志

Objective:To study the characteristics and influencing factors of vaginal microbiota in normal pregnant women.Methods:This study was based on a cohort of pregnant women established in Anqing Municipal Hospital Affiliated to Anhui Medical University from February 2018 to February 2020. Vaginal samples of normal pregnant women who met the inclusion and exclusion criteria were ordered by the gestational weeks at sampling. Five samples were randomly selected from each gestational week group and if the samples were less than five, all samples were included. Sequencing of the V3-V4 region of the 16S rRNA gene was performed. Dominant species were analyzed by MicrobiomeAnalyst. Alpha diversity was measured with Chao1, Observed Features, Shannon diversity, Simpson diversity, Faith_pd and Pielou′s Evenness. The dominant status of Lactobacillus was also described and compared. Multiple linear regression and logistic regression were used to analyze the factors influencing vaginal microbiota. Analysis of variance and Kruskal Wallis test were used for statistical analysis of continuous variables, and Chi-square test and Fisher′s exact test were used for categorical data. The differences were considered statistically significant when the P value was less than 0.05. Results:This study enrolled 91 pregnant women (91 vaginal samples) with an average age of (27.37±3.60) years. There were 18, 56 and 17 vaginal samples collected at the median gestational age of 11.93 weeks (the first trimester), 19.43 weeks (the second trimester) and 38.29 weeks (the third trimester), respectively. The relative abundance of Firmicutes and Lactobacillus was 91.30% and 87.67%, respectively. Lactobacillus iners and Lactobacillus crispatus had a relative abundance of 43.95% and 36.33%, respectively. Moreover, Lactobacillus iners-dominated vaginal microbiota was detected in all trimesters. The number of samples with high relative abundance of Lactobacillus iners gradually decreased with gestational age. Lactobacillus crispatus-dominated vaginal microbiota was found in the second and third trimesters and the number of samples with high relative abundance gradually increased during pregnancy. The Alpha diversity of vaginal microbiota had a decreasing trend during the gestation. There were significant differences in Pielou′s Evenness diversity index of vaginal microbiota between different smoking groups ( P<0.05) and in Shannon diversity index between different drinking groups ( P<0.05). There were significant differences in Chao1, Observed Features and Faith_pd diversity index of vaginal microbiota between pregnant women with different education ( P<0.05) and in Shannon and Simpson diversity index between different income groups ( P<0.05). Conclusions:Vaginal microbiota was dominated by Lactobacillus in normal pregnant women. The dominance of Lactobacillus iners gradually decreased, while that of Lactobacillus crispatus increased during gestation. In normal pregnant women, the Alpha diversity of vaginal microbiota was correlated with smoking, drinking, education and family annual income. Smoking cessation and drinking before pregnancy were related to lower Alpha diversity of vaginal microbiota in pregnant women, while lower education and higher family income were associated with higher Alpha diversity.

Relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity / 中华内分泌代谢杂志

Objective:Explore the relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity(baPWV) in community population.Methods:Questionnaire, physical examination, blood tests, and baPWV detection were applied to a community based population. Finally, 3 912 subjects with complete data were included in the study. The relationship between sleep duration, time to fall asleep and PWV was evaluated with binary logistic regression analysis. Results:Being adjusted for age, sex, prevalence of diabetes, sleep condition, body mass index, blood glucose, blood pressure, dyslipidemia, ankle-brachial index, sleep duration and time to fall asleep were correlated with PWV. The risk of PWV abnormalities was increased in the≥8 h group compared to the 6-8 h group( OR=1.155, 95% CI 0.995-1.367, P=0.037). The risk of abnormalities PWV was higher in the group with sleep time after 00: 00 than in the group -23: 00( OR=1.482, 95% CI 1.008-2.179, P=0.045). Conclusion:Long sleep duration(≥8 h) and late sleep time(after 00: 00) may be associated with higher risk of atherosclerosis.

Optimization of processing technology of Portulaca oleracea charcoal and its improvement effect on the symptom of hemorrhoid model rats / 中国药房

OBJECTIVE To optimize th e p rocessing technology of Portulaca oleracea charcoal，and to investigate its improvement effect on the symptom of hemorrhoid model rats. METHODS The effects of roasting temperature ，dosage and roasting time on the processing technology of P. oleracea charcoal were investigated with Box-Behnken response surface methodology using comprehensive score of tannin content ，water-soluble extract content and appearance properties as the index. The optimal process parameters are selected and verified. The hemorrhoid model rats were treated with P. oleracea charcoal（0.8 g/mL）prepared by the optimal processing technology ，once a day ，for 11 days. After last medication ，the perianal pathological score of hemorrhoid model rats were performed ；serum levels of tumor necrosis factor α（TNF-α），interleukin 6（IL-6）and IL- 1β were detected. RESULTS The optimal processing technology of P. oleracea charcoal included roasting temperature of 200 ℃， dosage of 150 g and roasting time of 14 min. Results of validation test showed that the comprehensive score of P. oleracea charcoal was 92.57，and relative error of it with predicted value （96.59）was －4.13％. External use of P. oleracea charcoal 0.8 g/mL prepared by the optimal processing technology could significantly promote the wound healing of hemorrhoid model rats ，reduced the amount of exudate ，and decreased the levels of TNF-α，IL-6 and IL-β in serum. CONCLUSIONS The optimized processing technology of P. oleracea charcoal is feasible. P. oleracea charcoal prepared by the optimized processing technology has good curative effect on the symptom of hemorrhoid model rats.

Pharmacological Effect and Mechanism of Andrographolide： A Review / 中国实验方剂学杂志

Andrographolide， a diterpene lactone， is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata （Burm.f.）Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation， bacteriostat， anti-virus， anti-tumor， protecting liver， promoting the function of gallbladder， and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific， it can inhibit nuclear factor-κB （NF-κB）， signal transduction and activator of transcription 3 （STAT3）， and other signaling pathways， reduce the synthesis and release of downstream inflammatory mediators， and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time， it suppresses a variety of tumor cells by inhibiting tumor cell proliferation， blocking cell cycle， and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， NF-κB， and secreted glycoprotein/β-catenin （Wnt/β-catenin）. In addition， it can also alleviate diabetes by regulating glucose metabolism. According to related research， it often exerts pharmacological effects through multiple pathways and multiple targets， but the specific targets are unclear. Therefore， this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions， which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.

Anti-tumor Effect of Shikonin： A Review / 中国实验方剂学杂志

The incidence and mortality of cancer are increasing year by year， seriously threatening human health. At present， the chemotherapy-based treatment of cancer can prolong the survival time of patients， but its severe side effects and adverse reactions often lead to poor prognosis. Therefore， searching for anti-cancer drugs with high efficiency and low toxicity has become the focus of clinical attention from all over the world. The effective components of Chinese medicine have the advantages of mild side effect and multi-target regulation， and their anti-tumor activities are highly favored by many researchers. Shikonin， a naphthoquinone compound， is the main effective component of Arnebiae Radix， with anti-tumor， anti-inflammatory， antioxidant， and other pharmacological effect. Studies have shown that shikonin possesses significant anti-tumor activities against a variety of tumor cells， and it can inhibit the development of many cancers， such as breast cancer， lung cancer， liver cancer， cervical cancer， ovarian cancer， colon cancer， and prostate cancer. The anti-tumor mechanism of shikonin is mainly related to multi-pathway and multi-target inhibition of tumor cell proliferation， the promotion of reactive oxygen species （ROS） production， induction of tumor cell apoptosis， cell cycle arrest， and tumor cell autophagy， and the inhibition of tumor cell migration and invasion. In addition， shikonin can increase the sensitivity of tumor cells to anti-tumor drugs and reverse the drug resistance of tumor cells. The signaling pathways involved in the anti-tumor effect of shikonin include phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， PI3K/Akt/mammalian target of rapamycin （mTOR）， mitogen-activated protein kinase （MAPK）， pyruvate kinase M2/signal transducer and activator of transcription protein 3 （PKM2/STAT3）， and Kelch-like epichlorohydrin-related protein 1/nuclear factor E2-related factor 2 （Keap1/Nrf2）. The anti-tumor effects are mainly achieved through the regulation of the PI3K/Akt signaling pathway. Based on the relevant literature on the anti-tumor effect and mechanism of shikonin in China and abroad， the present study reviewed the research progress in the past three years to provide useful references for the further study of the anti-tumor effect of shikonin and the research and development of new antineoplastic drugs.

Apigenin Induces Apoptosis of Human Colorectal Cancer CL187 Cells via PI3K/Akt and MAPK Signaling Pathways / 中国实验方剂学杂志

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L-1）. The blank group had higher protein level of Akt than the 60 mg·L-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

Apigenin Induces Apoptosis of Human Colorectal Cancer CL187 Cells via PI3K/Akt and MAPK Signaling Pathways / 中国实验方剂学杂志

ObjectiveTo study the effect of apigenin on the proliferation and apoptosis of human colon cancer CL187 cells and the underlying mechanisms. MethodHuman colorectal cancer CL187 cells were treated with different concentrations of apigenin （0， 30， 45， 60 mg·L-1） according to the results of the preliminary experiment. The proliferation of CL187 cells was detected by methyl thiazolyl tetrazolium （MTT） and colony formation assays， and the apoptosis was observed via Hoechst 33258 staining. Real-time fluorescence quantitative PCR was conducted to determine the mRNA levels of cysteine protease-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the CL187 cells treated with apigenin. Western blot was employed to measure the protein levels of Caspase-3， Bcl-2， and Bax associated with apoptosis， protein kinase B （Akt） and phosphorylated Akt （p-Akt） in phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway， and extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， c-Jun N-terminal kinase （JNK）， p-JNK， p38 mitogen-activated protein kinase （MAPK）， and p-p38 MAPK protein in MAPK pathway. ResultCompared with the blank group， the apigenin groups had low cell survival rates and high inhibition rates on cell proliferation （P<0.01）. Apigenin decreased the cell clone number and clone formation rate， and increased the inhibition rate on clone formation （P<0.01）. After CL187 cells were treated with different concentrations of apigenin for 48 h， typical apoptosis characteristics such as nuclear pyknosis， chromatin condensation， and enhanced fluorescence reaction were observed. Compared with blank group， 45， 60 mg·L-1 apigenin treatments down-regulated the mRNA level of anti-apoptotic gene Bcl-2 （P<0.01） and all the apigenin treatments up-regulated those of the pro-apoptotic genes Bax and Caspase-3 （P<0.05， P<0.01）. Similarly， apigenin treatments down-regulated the protein level of Bcl-2 （P<0.05， P<0.01） and up-regulated those of Caspase-3 （P<0.05， P<0.01） and Bax （P<0.01， 45， 60 mg·L-1）. The blank group had higher protein level of Akt than the 60 mg·L-1 apigenin group （P<0.01）， higher protein levels of p-Akt， ERK1/2， and p-ERK1/2 than the 45， 60 mg·L-1 apigenin groups （P<0.01）， and higher protein levels of JNK and p-JNK than the apigenin groups （P<0.05， P<0.01）. Compared with blank group， 60 mg·L-1 apigenin up-regulated the protein level of p38 MAPK （P<0.05）， and all the apigenin groups up-regulated that of p-p38 MAPK （P<0.01）. Furthermore， apigenin lowered the p-Akt/Akt ratio （P<0.05， P<0.01） and p-ERK1/2/ERK1/2 ratio （P<0.01）， while it increased the p-JNK/JNK ratio （45， 60 mg·L-1； P<0.05， P<0.01） and p-p38 MAPK/p38 MAPK ratio （P<0.05， P<0.01）. ConclusionApigenin can inhibit the proliferation and promote the apoptosis of CL187 cells by inhibiting the PI3K/Akt signaling pathway and regulating the expression of proteins in the MAPK signaling pathway.

Research progress of pharmacological action and mechanism of piperine / 中国药房

Piperine is a kind of amide alkaloids presenting in Piper nigrum L.，which has the pharmacological action such as protecting cardiovascular system ，regulating glucose and lipid metabolism ，anti-tumor，improving nervous system diseases ， anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ，as the main active ingredient of P. nigrum ，could protect the cardiovascular system by reducing inflammation and oxidative stress ；improve mitochondrial function through anti-inflammatory and antioxidant effects ，thereby regulate glucose and lipid metabolism ；play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin，NF-κB/Nrf-2/KeAP-1/HO-1， PI3K/Akt，TGF-β1/Smad2/ERK1/2；improve neurological diseases by inhibiting autophagy ，relieving inflammation ，improving antioxidant，inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ；play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However，the mechanism of action of piperine is not perfect ，and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ，without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ，the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Outcomes of newly diagnosed prediabetes and its risk factors in Guiyang: a 3-year follow-up study / 中华内分泌代谢杂志

Objective:To investigate the outcomes and influencing factors of newly diagnosed prediabetic subjects aged 40 years and above in Guiyang.Methods:A total of 10 015 residents aged 40 years and above were recruited from the Yunyan community, Guiyang, from May to August 2011. Physical examination, laboratory measurements, and questionnaires were conducted. The follow-up survey was conducted in July 2014. A total of 2 530 newly diagnosed prediabetic subjects at baseline were included in the analysis.Results:The 3-year cumulative morbidity of diabetes mellitus was 14.3%, and the risk of diabetes mellitus in combined impaired fasting glucose(IFG)and impaired glucose tolerance(IGT)groups was significantly higher than that in isolated IFG(i-IFG)or isolated IGT(i-IGT)group( P<0.01). High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes( OR=1.836, 95% CI 1.374-2.454; OR=1.398, 95% CI 1.261-1.550; OR=2.526, 95% CI 1.804-3.538, all P<0.01)and the inhibitory factors for reversion to normal glucose tolerance( OR=0.511, 95% CI 0.409-0.638; OR=0.715, 95% CI 0.661-0.774; OR=0.638, 95% CI 0.500-0.816, all P<0.01). High level of high density lipoprotein-cholesterol(HDL-C)was an promoting factor for reversion to normal glucose tolerance( OR=1.306, 95% CI 1.017-1.678, P=0.036). Subjects in the highest tertile of baseline HbA 1C level and body mass index(BMI)change before and after follow-up(ΔBMI=follow-up BMI minus baseline BMI)had a higher risk of diabetes mellitus than those in the lowest tertile( OR=2.398, 95% CI 1.733-3.322; OR=2.402, 95% CI 1.859-3.105, both P<0.01). The risk of diabetes mellitus in the significant weight loss group was reduced by 40.4% compared with the non-significant weight loss group when the subjects were divided into two groups according to the cutoff of the lower tertile of ΔBMI( RR=0.596, 95% CI 0.463-0.766, P<0.01). Conclusion:The risk of diabetes mellitus in combined IFG/IGT group was significantly higher than that in i-IFG or i-IGT group. High baseline fasting plasma glucose, 2 h plasma glucose, and HbA 1C levels were the independent risk factors for the development of diabetes. High level of HDL-C was an promoting factor for reversion to normal glucose tolerance. Weight loss can significantly reduce the risk of progression to diabetes in individuals with prediabetes.

Diagnostic value of 18F-FDG PET/MR for liver metastasis / 中华核医学与分子影像杂志

Objective:To explore the diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/MR imaging for liver metastasis. Methods:A retrospective analysis of 75 cases (46 males, 29 females; age (58.9±14.3) years) with suspected liver metastases from January 2020 to October 2020 in Ruijin Hospital were performed. All patients underwent PET/MR and enhanced upper abdominal CT scans. Diagnostic efficacies of enhanced CT, PET, MR and PET/MR for liver metastases (based on lesions and patients respectively) were calculated and compared (McNemar test).Results:A total of 306 liver lesions were detected in 75 patients, of which 179 lesions in 45 patients were confirmed as liver metastases through follow-up or pathology. In lesion-based analysis, the sensitivities of enhanced CT, PET, MR and PET/MR were 74.9%(134/179), 60.3%(108/179), 98.9%(177/179) and 100%(179/179), with specificities of 96.9%(123/127), 100%(127/127), 92.9%(118/127) and 92.1%(117/127), respectively. The diagnostic efficacy of PET/MR was significantly higher than that of enhanced CT and PET ( χ2 values: 51.000 and 81.000, both P<0.001), but there was no statistical difference between PET/MR and MR ( χ2=2.000, P=0.368). In patient-based analysis, the sensitivities of enhanced CT, PET, MR and PET/MR were 82.2%(37/45), 84.4%(38/45), 95.6%(43/45) and 100%(45/45), with specificities of 86.7%(26/30), 100%(30/30), 70.0%(21/30) and 70.0%(21/30), respectively. The diagnostic efficacies of enhanced CT and PET were statistically different from PET/MR ( χ2 values: 13.000 and 16.000, both P<0.05), but there was no statistical difference between MR and PET/MR ( χ2=2.000, P=0.368). Conclusions:Compared with enhanced CT, PET and MR, 18F-FDG PET/MR has a higher detective rate for liver metastases. The overall diagnostic efficacy of 18F-FDG PET/MR is better than enhanced CT and PET alone, but similar to MR.

Evaluation of left ventricular diastolic function by strain rate parameters in patients with coronary artery disease without regional wall motion abnormalities / 中华超声影像学杂志

Objective:To investigate the value of early diastolic strain rate (e′SR) and peak value of early diastolic velocity (E) to e′SR (E/e′SR) in predicting the severity of coronary lesions in patients with coronary artery disease (CAD) without regional wall motion abnormalities (RWMA) and with preserved left ventricular ejection fraction (LVEF).Methods:A selection of 70 patients with CAD without RWMA and with preserved LVEF (>50%) admitted to Zhengzhou University People′s Hospital from October 2020 to March 2021 were collected and divided into two groups according to the Gensini score method: low group with a score<34 and high group with a score≥34. Another 30 healthy volunteers with matching gender and age at the same period were selected as the control group. Cardiac structural parameters left atrium diameter (LAD), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), interventricular septum diastolic diameter (IVST), left atrial volume (LAV), E, peak value of late diastolic velocity (A) of mitral inflow, peak value of early diatolic tissue Doppler velocity of septal and lateral walls of mitral annulus and LVEF were routinely measured. Left atrial volume index (LAVI), mean of peak value of early diatolic tissue Doppler velocity of septal and lateral walls of mitral annulus (e′), E/e′were calculated. Speckle tracking imaging (STI) technique was used to collect systolic left ventricular global longitudinal strain (GLS) and e′SR, E/e′SR was calculated. The differences in each parameter among the three groups were compared. The ROC curve was used to obtain the best cut-off values of e′SR and E/e′SR for predicting the severity of coronary lesions in CAD patients, respectively, and the corresponding sensitivity and specificity were obtained, respectively.Results:Compared with the control group, LAV and LAVI were increased in the high group (all P<0.05). Compared with the control and the low group, e′ was decreased and E/e′ was increased in the high group (all P<0.05). Compared with the control group, e′SR and GLS were decreased and E/e′SR were increased in the high and low groups (all P<0.05). Compared with the low group, e′SR and GLS were decreased and E/e′SR was increased in the high group (all P<0.05). ROC curve analysis showed that the maximum area of E/e′SR under the curve was 0.717. When the Youden index was maximum, its best cut-off value was 0.75 m, and corresponding sensitivity and specificity were 60.0% and 85.7%, respectively. The maximum area under the e′SR curve was 0.785. When the Youden index was maximum, its best cut-off value was 1.12 s -1, and the corresponding sensitivity and specificity were 85.7% and 68.6%, respectively. Conclusions:For CAD patients without significant RWMA and with preserved LVEF, left ventricular diastolic and systolic function may be impaired to varying degrees, manifesting as decreased e′SR, increased E/e′SR, decreased GLS. The parameters of diastolic strain rate are a reliable basis for early detection of impaired diastolic function in CAD patients, and have certain clinical significance for predicting the severity of coronary lesions.

Research Progress on Pharmacological Effect and Mechanism of Polydatin / 中国实验方剂学杂志

Polydatin， a polyphenolic compound， is the main active component of Chinese medicine Polygoni Cuspidati Rhizoma et Radix and has a variety of pharmacological activities. In recent years， there are more studies on the pharmacological effects and mechanisms of polydatin. Modern pharmacological studies show that polydatin has protective effects on the nervous system， cardio-cerebral vascular system， and respiratory system， and also has significant effects on the liver， kidney， lung， and other organs. Its effect of regulating blood glucose and blood lipid on atherosclerosis is significant， and the anti-fibrosis effect is significant on the liver and kidney. Polydatin can inhibit many types of tumor cells， suppress proliferation and induce apoptosis of tumor cells. Polydatin can also resist inflammation and radiation， protect bone marrow， and promote wound healing. Based on the literature on the pharmacological effects of polydatin， the authors found that the single pharmacological mechanism of polydatin is often regulated by multi-target proteins and multiple pathways， but the most of action targets are unclear， which needs to be further investigated. This study summarized the research progress on the pharmacological action and mechanism of polydatin in the past five years and put forward some suggestions on its present research situation and future research direction to broaden the research ideas of researchers and speed up the identification of the targets of its pharmacological effect. This study is expected to provide a scientific theoretical basis for the further development and utilization of polydatin.

Mechanisms and influencing factors of cataract occurrence or progression after vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Since first proposed by O'Malley in 1972, the revolutionary vitrectomy has brought ophthalmic surgery into a new era, bringing hope to countless patients with vitreoretinal diseases. With the development of surgical techniques, increased safety and effectiveness, and expanded surgical indications, vitrectomy has become the most common surgical treatment for various posterior segment diseases. Though there is a trend of decreasing in postoperative complications, the occurrence and progression of cataract remains the most common complication after vitrectomy. As cataract would compromise the postoperative vision and fundus observation, cataract extraction surgery is always inevitable, which seriously increases the burden of patients. The pathogenesis of cataract is till inconclusive. There are currently many hypotheses including increased oxygen partial pressure around the lens, destruction of the vitreous structure, and phototoxicity. This article reviews the incidence, mechanism and influencing factors of cataract occurrence or progression after vitrectomy, aiming to provide more evidence for further investigation of pathogenesis, prevention and treatment for post-vitrectomy cataract.