Menaquinone-4 exerts a protective effect against carbon tetrachloride-induced acute liver injury in mice by alleviating ferroptosis / 临床肝胆病杂志

ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.

Buyang Huanwu Decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury / 中国结合医学杂志

OBJECTIVE@#To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP).@*METHODS@#The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining.@*RESULTS@#The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01).@*CONCLUSIONS@#BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.

Influence of the Pre-shock State on the Prognosis of Medical Patients with Sepsis: A Retrospective Cohort Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the pre-shock state on the mortality of patients with sepsis.@*METHODS@#We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates.@*RESULTS@#A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points.@*CONCLUSION@#The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.

Value of three hemolysis tests and carboxyhemoglobin in the diagnosis of hemolytic disease of the fetus and newborn / 中国输血杂志

【Objective】 To investigate the value of three hemolysis tests and carboxyhemoglobin (COHb) level in the diagnosis of hemolytic disease of the fetus and newborn (HDFN). 【Methods】 From January 1, 2019 to December 31, 2022, the neonates hospitalized in the Department of Neonatology of Hebei Provincial Children's Hospital with suspected hemolytic disease who had serological testing were retrospectively enrolled in the study. They were distributed into HDFN group and non-HDFN group according to the final diagnosis. Their clinical and laboratory data were collected and analyzed, and the COHb level was detected by blood gas analyzer. 【Results】 A total of 378 neonates with HDFN and 217 neonates without HDFN were included in the study. Most of the neonates in HDFN group were full-term infants (348/378, 92.1%), with median gestational age of 39.1 (38.3, 40.0) weeks. Three hundred and fifty-four cases (354/378, 93.7%) were ABO-HDFN and the rest were Rh HDFN. There were significant differences in the level of serum total bilirubin, hemoglobin, COHb and reticulocyte percentage at admission between the two groups(P<0.05). The positive rate of three hemolysis tests in HDFN group decreased with the increase of the days after birth. The highest positive rate (more than 80%) was observed within 2 days after birth. Correlation analysis showed a negative relationship between the COHb level and the age (rs = -0.434, P<0.001) . Among the three hemolysis tests in HDFN group, the positive rate of antibody release test was the highest (69.0%), followed by the free antibody test (55.6%) and the direct antiglobulin test (DAT) (36.0%). Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value of COHb was 1.15%.The sensitivity of COHb ≥ 1.15% was 51.8%, higher than single DAT (36.0%) . The diagnosis effectiveness of three hemolysis tests couldn't be improved when combined with COHb detection(Z = -0.727, P>0.05) . 【Conclusion】 The three hemolysis tests are important in the diagnosis of HDFN, among which the antibody release test has the highest sensitivity. COHb has certain value for the diagnosis of HDFN, but joint testing cannot improve the diagnosis effectiveness of three hemolysis tests. Hemolysis tests and/or COHb detection should be conducted for neonates at risk of hemolysis as early as possible after birth.

Microbial transformation of artemisinin and its derivatives / 中国中药杂志

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Research status and progress of health literacy for children and adolescents / 中国学校卫生

Abstract@#Improving health literacy can effectively reduce the risk of health risk behaviors and adverse health outcomes in children and adolescents. Global research on health literacy of children and adolescents has been increasing in recent years. The paper reviews the existing research and proposes that there is no universal definition and connotation of health literacy for children and adolescents, most of the studies use or make some revisions on the definition of adult health literacy in child and adolescent health literacy, failing to consider developmental characteristics and unique health needs of children and adolescents. Moreover, the assessment index system and instruments are diversified, making the research findings from different studies difficult to compare, and to obtain consistent and reliable conclusions. Future endeavors are encoouraged to expand health literacy researches and to update more comprehensive and practical definition, and to develop a standardized assessment instrument that can be validated in Chinese culture.

Knowledge of comprehensive sexuality education and influencing factors among junior high school teachers / 中国学校卫生

Objective@#To understand knowledge of comprehensive sexuality education and its associated factors among junior high school teachers in six provinces in China, in order to provide a scientific basis for teacher training.@*Methods@#From June to December 2021, a convenience sampling method was used to select 1 016 junior high school teachers from Beijing, Chongqing, Liaoning, Sichuan, Yunnan and Guangdong provinces. A structured questionnaire was used to investigate teachers knowledge of comprehenswe sexuality education. Binary Logistic regression was used to analyze the related influencing factors of the knowledge of comprehensive sexuality education among junior high school teachers.@*Results@#The study showed that the knowledge rate of comprehensive sexuality education among middle school teachers was 58.1%, and the knowledge rate was higher in teachers who had conducted sexuality education to students( χ 2=9.42, P <0.01). The percentage of the correct answer on the prevention and control of sexually transmitted diseases(26.0%), the impact of inequality on love relationships( 33.6 %), and the impact of mass media on sexual cognition(68.8%) was the lowest. Regardless of whether they had implemented sexuality education for students, the knowledge and awareness rate of sexual knowledge among biology teachers, school doctors/health teachers and mental health teachers was higher( OR=2.32, 4.17, P <0.05).@*Conclusion@#Knowledge of comprehensive sexuality education among middle school teachers still needs to be improved. It is advisable to strengthen the training of comprehensive sexuality education for middle school teachers and focus on teachers of subjects related to comprehensive sexuality education.

Survey on the current situation and influencing factors of humanistic care ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City / 中华劳动卫生职业病杂志

Objective: To investigate the humanistic care consciousness and ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City. Methods: In June 2021, a total of 345 outpatient and emergency nurses from 6 tertiary Grade A hospitals in Zhengzhou City were selected as the survey objects by random number table method. The humanistic care ability of outpatient and emergency nurses was investigated. Multiple linear regression analysis was used to analyze the related factors influencing the humanistic care ability of outpatient and emergency nurses. Results: The total score of humanistic care ability of outpatient and emergency nurses in Zhengzhou tertiary Grade A hospital was (194.18±30.53). The scores of humanistic care ability of outpatient and emergency nurses with different gender, age, educational background, professional title, length of service, night shift frequency, marital status, children's status, employment patterns and average monthly household income were significantly different (P<0.05). Regression analysis showed that education background, length of service, professional title and night shift frequency were independent influencing factors for outpatient and emergency nurses' humanistic care ability (β=0.243, 0.139, 0.163, -0.126, P<0.05) . Conclusion: At present, the humanistic care ability of outpatient and emergency nurses in tertiary Grade A hospitals in Zhengzhou City is still low. Education, length of service, professional title and night shift frequency are independent influencing factors affecting the humanistic care ability of nurses.

Analysis of urinary arsenic methylation metabolites in population exposed to arsenic through drinking water before and after water improvement / 中华地方病学杂志

Objective:To study the effect of water improvement on urinary arsenic methylation metabolism in population exposed to arsenic through drinking water.Methods:A cluster sampling method was used to select drinking water type arsenism areas in Bayannur City, Inner Mongolia Autonomous Region. Permanent residents lived in the arsenism areas for more than 10 years were selected as the survey subjects. Urine samples ( n = 874, 111, 145) were collected in 2004 (before water improvement), 2014 (4 years after water improvement) and 2017 (7 years after water improvement), respectively, and some subjects were followed up in 2014 and 2017. High performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect different forms of arsenic metabolites in urine [inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA)], and total arsenic (tAs), the iAs percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), monomethylation rate (PMI), dimethylation rate (SMI), and the ratio of MMA to DMA (MMA/DMA) were calculated. The content and distribution of urinary arsenic metabolites in people exposed to arsenic before and after water improvement were compared and analyzed. Results:Compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine of arsenic exposed population in 2014 were lower ( Z =-14.12,-12.79,-14.27,-14.21,-6.90, P < 0.001), the levels of MMA%, DMA% and PMI were higher ( Z =-3.22,-2.91,-6.90, P < 0.05); in the same drinking water arsenic exposed population, compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine ( n = 48) were lower ( Z =-5.57,-5.53,-5.54,-5.55,-2.86, P < 0.05) in 2014, and PMI level was higher ( Z =-2.86, P = 0.004). Compared with 2014, the levels of iAs% and MMA/DMA in urine of arsenic exposed population in 2017 were lower ( Z =-4.97,-2.25, P < 0.05), the levels of MMA, DMA, tAs, DMA%, PMI and SMI were higher ( Z =-4.01,-5.39,-4.77,-4.61,-4.97,-2.25, P < 0.05); in the same drinking water arsenic exposed population, compared with 2014, the level of iAs% in urine ( n = 28) was lower ( Z =-2.87, P = 0.004) in 2017, the levels of DMA% and PMI were higher ( Z =-2.32,-2.87, P < 0.05). Conclusion:Water improvement could significantly reduce the levels of urinary arsenic metabolites iAs, MMA, DMA and tAs and increase the level of DMA% in arsenic exposed population.

Changes in the structure of intestinal mucosal flora in colorectal cancer patients / 南方医科大学学报

OBJECTIVE@#To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC).@*METHODS@#We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit.@*RESULTS@#The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001).@*CONCLUSION@#The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.

Analysis on Medication Regularity of Traditional Chinese Medicine in Treatment of Intermediate and Advanced Non-small Cell Lung Cancer Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore medication regularity of traditional Chinese medicine （TCM） in the treatment of non-small cell lung cancer （NSCLC） and thereby to lay a theoretical basis for clinical medication and drug development. MethodArticles on clinical treatment of intermediate and advanced NSCLC with TCM in the past 40 years were retrieved from CNKI， which were taken the data source. Then the articles were screened to establish a formula database， followed by frequency statistics， association rule analysis， cluster analysis， factor analysis， and complex network construction. ResultA total of 307 eligible articles were screened out， involving 483 formulas. The common syndrome of intermediate and advanced NSCLC was the deficiency of both Qi and Yin， with the common syndrome elements of Qi deficiency， Yin deficiency， phlegm， blood stasis， pathogenic heat （fire）， toxin， and pathogenic dampness. The frequently used medicinals mainly had the functions of tonifying deficiency， clearing heat， resolving phlegm and relieving cough and dyspnea， promoting urination and draining dampness， and activating blood and resolving stasis. The high-frequency medicinals were Astragali Radix， Glycyrrhizae Radix et Rhizome， Ophiopogonis Radix， Fritillariae Thunbergii Bulbus， and Poria， which were mainly cold， bitter， sweet， and pungent， with tropism at lung， spleen， and stomach. The association rule analysis yielded 17 rules with strong association. Ten common factors were extracted from the factor analysis， and cluster analysis classified the medicinals into 5 groups. Complex network analysis suggested that the core formula was modified Liujunzi Tang and Yiqi Yangyin Jiedu prescription. ConclusionThe treatment principle for intermediate and advanced NSCLC is replenishing Qi and nourishing Yin， invigorating spleen and resolving phlegm， clearing heat and detoxifying， promoting blood circulation and removing blood stasis. The core combinations new prescription discovered by data mining are of important guiding significance， but they should be further verified in clinical practice and by experiments based on the theory of TCM.

Preparation of Rehmanniae Radix Juice for Baihe Dihuangtang Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveTo compare the four preparation methods of Rehmanniae Radix juice described in ancient literature and find the method that is most suitable for the preparation of Rehmanniae Radix juice used in Baihe Dihuangtang. MethodThe ancient medical books record four methods for preparing Rehmanniae Radix juice： crushing fresh Rehmanniae Radix for juice， steaming fresh Rehmanniae Radix for juice， boiling fresh Rehmanniae Radix for juice， and boiling dry Rehmanniae Radix for juice. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was employed to detect the compounds in the four juice samples， followed by principal component analysis （PCA）. Result① Totally 27 compounds were identified in the juice samples， including 10 iridoid glycosides， 14 phenylethanoid glycosides， 2 phenolic acids， and 1 irisone. Among them， 15 common compounds were shared by the four juice samples， including 7 iridoid glycosides， 7 phenylethanoid glycosides， and 1 phenolic acid. ② Five common compounds in the four juice samples can be matched with the reference standards， which were catalpol， aucubin， rehmannioside D， ajugol， and purpureaside C. ③ Verbascoside and isoacteoside were not detected in the juice prepared by crushing fresh Rehmanniae Radix， while it was detected in the other three juice samples， which indicated that the two components were produced after heating rather than being the original components in fresh Rehmanniae Radix. ④ The comparison of the ion fragments demonstrated that verbascoside was produced from purpureaside C after the cleavage of the glycosidic bond and removal of a molecule of mannose. ⑤ Isoacteoside could be isomerized from verbascoside， and its relative content increased with the extension of heating time. However， the relative content of verbascoside and purpureaside C did not decrease significantly. Therefore， it was hypothesized that purpureaside C was produced from its upstream component. ConclusionThe juice prepared by crushing fresh Rehmanniae Radix has the chemical composition significantly different from the juice samples prepared with the other 3 methods， while the latter 3 juice samples had similar chemical composition. Although all the four methods can be used， it is more suitable to prepare Rehmanniae Radix juice by steaming fresh Rehmanniae Radix， boiling fresh Rehmanniae Radix， and boiling dry Rehmanniae Radix.

Effect of Danggui Niantongtang on Expression of Autophagy-related Proteins LC3， Beclin1 and p62 in Rats with Adjuvant Arthritis Differentiated into Wind-damp-heat Impediment / 中国实验方剂学杂志

ObjectiveTo observe the preventive and control effects of Danggui Niantongtang against adjuvant arthritis differentiated into wind-damp-heat impediment in rats and its influences on the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 （LC3）， homolog of yeast Atg6 （Beclin1） and p62. MethodThe six-week-old male SD rats were randomly divided into the normal group， wind-damp-heat impediment model group， low-， medium-， and high-dose Danggui Niantongtang （5.67， 11.34， 22.68 g·kg-1） groups， and methotrexate （MTX， 1.35 mg·kg-1） group， with 10 rats in each group. A rat model of adjuvant arthritis was established by subcutaneous injection of inactivated Mycobacterium tuberculosis into the tail root， followed by exposure to the manual climatic box for 16 d for inducing the wind-damp-heat impediment. The drugs were administered intragastrically on the day of immunization for 28 d. The general conditions of rats were observed and the swelling degree of toes and arthritis index （AI） were detected. The pathological changes in the synovial tissues of the knee joints were observed by hematoxylin-eosin （HE） staining. The mRNA expression levels of LC3， Beclin1， and p62 in the synovial tissues were measured by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， followed by the assay of their protein expression by Western blot and immunohistochemistry. ResultCompared with the normal group， the wind-damp-heat impediment model group exhibited significantly increased swelling degree of toes （P<0.01）， increased AI （P<0.01）， proliferated synovial cells （P<0.01）， up-regulated LC3 and Beclin1 protein and mRNA expression （P<0.01）， and down-regulated p62 protein and mRNA expression （P<0.01） after 16， 20， 24， 28-d medication. Compared with the wind-damp-heat impediment model group， each medication group displayed alleviated toe swelling and synovial hyperplasia to different degrees， decreased mRNA and protein expression levels of LC3 and Beclin1 （P<0.01）， and increased p62 mRNA and protein expression （P<0.05，P<0.01）， with the best outcomes observed in the medium-dose Danggui Niantongtang group. ConclusionDanggui Niantongtang effectively relieves adjuvant arthritis due to wind-damp-heat impediment in rats， which may be related to its regulation of the expression of autophagy-related proteins LC3， Beclin1， and p62 and the inhibition of autophagy.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Effect of Danggui Niantongtang on Key Factors of Extrinsic and Intrinsic Apoptotic Pathway in Synovial Tissue of Adjuvant Arthritis Rats / 中国实验方剂学杂志

Objective:To observe the effect of Danggui Niantongtang on the protein and mRNA expression of key regulatory factors of the extrinsic and intrinsic apoptotic pathway in synovial tissue of adjuvant arthritis （AA） rats， and to further explore the mechanism of Danggui Niantongtang in the prevention and treatment of rheumatoid arthritis. Method:The general condition of AA rats， including its body weight， were observed. The changes of toe volume were detected by toe volume meter. Histopathological changes of synovium of knee joint were observed by hematoxylin-eosin （HE） staining. The mRNA and protein expression levels of tumor necrosis factor receptor super family 6 （Fas）， Fas-associating protein with a novel death domain（FADD）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase Caspase-3 （Caspase-3） were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the normal group， the toe volume of the model group increased significantly （<italic>P</italic><0.01）， with significantly proliferated synovial cells， significantly reduced mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 in synovial tissues（<italic>P</italic><0.05，<italic> P</italic><0.01）， and significantly increased Bcl-2 level （<italic>P</italic><0.01）. Compared with the model group， the swelling degree of toes in Danggui Niantongtang group and Tripterygium group was significantly alleviated （<italic>P</italic><0.01）， with significantly improved synovial hyperplasia， significantly increased mRNA and protein expression levels of Fas， FADD， Bax and Caspase-3 （<italic>P</italic><0.05， <italic>P</italic><0.01）， and significantly decreased expression levels of bcl-2 mRNA and protein （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Danggui Niantongtang can effectively reduce joint swelling and abnormal proliferation of synovial tissue in AA rats. Its mechanism may be related to regulating the expression of Fas， FADD， Bax， Bcl-2 and Caspase-3， and promoting the apoptosis of synovial cells.

Literature research and traditional Chinese medicine properties of Aspalathus linearis / 中国中药杂志

Aspalathus linearis is a needle-shaped shrub that grows in the Cedarberg mountains in southern South Africa, with an extremely high medicinal value. In 2014, China has approved A. linearis as a new food material. Through retrieval in CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus databases, the literatures were excluded, classified and summarized.On the basis of Chinese medicine theory, the traditional Chinese medicine properties were deducted. Finally, 264 relevant li-teratures were included and classified into 6 categories: review, planting, chemical composition, clinical study, pharmacological effects and safety. The traditional Chinese medicinal properties were deducted as sweet flavor and neutral property. It enters kidney, spleen, heart and liver channels. The major functions are to tonify the kidney and benefit the essence, nourish Qi and spleen, nourish Yin and prompt the production of body fluid, tranquilize mind, and relieve pain. It can be used for soreness of the waist and fatigue, sexual disinterest, limbs heaviness, thirst due to insufficiency of fluid and internal heat, irritability and insomnia, forget fulness, stomachache, joint pain, dysmenorrhea, headache. Preparation for external use can treat eczema itching. Water decoction(2-15 g) can also be used as tea directly. This paper defined the traditional Chinese medicine properties of A. linearis, so as to provide the theoretical basis for further clinical application.

Literature research of Passiflora incarnata and discussion of its traditional Chinese medicine properties / 中国中药杂志

Based on the research literatures of Passiflora incarnata and the theory of traditional Chinese medicine, the paper discussed the traditional Chinese medicinal properties of P. incarnate, so as to provide a theoretical basis for the compatibility and application of P. incarnata. The literature databases of CNKI, Wanfang, VIP, Web of Science, PubMed and Scopus were selected, and the literatures relating to P. incarnata were reviewed to screen out the scientific research literatures with a high credibility, rational design and reliable conclusions. Foreign pharmacopoeia was consulted, and the listed products were summarized. The traditional Chinese medicine properties of P. incarnata were studied based on 32 clinical trials, 66 pharmacological researches, 64 chemical constituents researches as well as the theory of traditional Chinese medicine. It was preliminarily concluded that the medicinal properties of P. incarnata are sweet, cool, and enter heart, liver channels. The function is mainly to calm the heart and tranquilizing the mind, and calm the liver wind. It is used for hyperactivity of liver-Yang, stagnation of liver-Qi, restlessness of mind, depression, nervousness, insomnia. This paper summarized the source, characteristics of natures, tastes and channel tropism, usage and dosage, function indications of P. incarnata, and defined its clear traditional Chinese medicine property, which lays a theoretical foundation for the compatibility and clinical application of P. incarnata and Chinese medicine.

A novel flavanone from Thymus przewalskii / 中国中药杂志

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavanone(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 μmol·L~(-1).

Analysis on formulation regularity and characteristics of acne-relieving Chinese medicinal health products and Chinese patent medicines / 中国中药杂志

This study summarized and analyzed the current acne-relieving Chinese medicinal health products and Chinese patent medicines,aiming at providing references for the formulation and development of acne-relieving health products. The information on acne-relieving health products published by the Department of Special Food Safety Supervision and Management,the State Administration for Market Regulation( SAMR) was retrieved,and the Chinese patent medicines on DRUGDATAEXPY were searched. Microsoft Excel and the Traditional Chinese Medicine Inheritance Support System V2. 5( TCMISS) were employed to statistically analyze the characteristics of formulations. Forty-three acne-relieving health products were obtained,including 40 ones containing Chinese herbal medicines. Six Chinese herbal medicines showed a usage frequency ≥8,with 61 times in use totally,including Salviae Miltiorrhizae Radix et Rhizoma( 13),Lonicerae Japonicae Flos( 12),Taraxaci Herba( 11),ALOE( 9),Carthami Flos( 8),and Rhei Radix et Rhizoma( 8). A total of 29 Chinese patent medicines with similar efficacy were collected in DRUGDATAEXPY. Nine Chinese herbal medicines showed a usage frequency ≥6,with 63 times in use,including Rhei Radix et Rhizoma( 10),Glycyrrhizae Radix et Rhizoma( 8),Scutellariae Radix( 8),Lonicerae Japonicae Flos( 7),Angelicae Sinensis Radix( 6),Paeoniae Radix Rubra( 6),Astragali Radix( 6),Paeoniae Radix Alba( 6),and Gardeniae Fructus( 6). Through unsupervised hierarchical entropy-based clustering of the above-mentioned Chinese medicinal health products and Chinese patent medicines,five and three new formulas were obtained,respectively. The selection of Chinese herbal medicines was consistent with the principles of traditional Chinese medicine( TCM) theories in relieving acne,i. e.,dispelling exterior wind,ventilating lungs,clearing heat,dissipating mass,promoting diuresis,relaxing bowels,removing toxin,activating blood,resolving stasis,eliminating phlegm,and regulating Qi. According to the " lung governing skin and body hair" and " interior-exterior relationship between lung and large intestine" in TCM theories,the idea that acne could be treated by relieving constipation was proposed,which provided new methods and references for the research and development of Chinese medicinal health products.