Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

Red cell membrane-coating Prussian blue for combined photothermal and NO gas therapy for nasopharyngeal carcinoma.

Nitric oxide (NO) gas molecules have demonstrated remarkable anti-tumor effects and minimal susceptibility to drug resistance, establishing as a promising modality for effective tumor treatment. However, how to realize its stable and efficient delivery in vivo is still a challenge. In this study, we have developed a heat-responsive biomimetic nano erythrocyte (M/B@R) by loading a NO donor (BNN6) onto mesoporous Prussian blue (M-PB) and subsequently enveloping them with red blood cell membranes. The preserved integrity of the red blood cell membrane (RBCm) structure could ensure its excellent biosafety, prolong its circulation time within the bloodstream and then enhance the accumulation of BNN6 at tumor sites. When M/B@R is stimulated by near-infrared light (NIR-II, 808 nm) irradiation, the nanoparticle could generate significant heat for photothermal therapy (PTT) by the characteristic NIR absorption of M-PB and then NO could also be efficiently released. The generated NO further facilitates the formation of ONOO-, a highly toxic species to tumors, while also alleviating tumor hypoxia. Remarkably, M/B@R, with NIR as the excitation source, induces combined lethality through hyperthermia, DNA damage, and tumor hypoxia relief. This novel combination strategy provides a new avenue for PTT/NO-induced cancer therapy.

Molecular targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis based on randomized controlled trials.

OBJECTIVE: The aim of this study was to compare and rank different targeted therapies or immunotherapies for advanced hepatocellular carcinoma based on efficacy. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane Library databases was conducted. All systematic treatment regimens that reported comparisons with sorafenib were included in this analysis. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and other outcome measures included the objective response rate (ORR) and safety analysis according to reported treatment-related adverse events. RESULTS: A total of 29 RCTs involving 13376 patients were included in the analysis, including 10 single-agent therapies and 17 combination therapies. Compared with sorafenib, sintilimab plus IBI305 (HR: 0.57, 95% CI: 0.43-0.75), camrelizumab plus rivoceranib (HR: 0.62, 95% CI: 0.49-0.78), and atezolizumab plus bevacizumab (HR: 0.66, 95% CI: 0.52-0.83) ranked in the top three in terms of OS. CONCLUSIONS: PD-1/PD-L1 inhibitors combined with anti-vascular endothelial growth factor (anti-VEGF)-targeting drugs have shown better therapeutic effects in the systematic treatment of patients with advanced hepatocellular carcinoma, and the combination of targeted and immune therapy modes should be further developed.

Progress in diagnosis and treatment of acute injury to the anterior talofibular ligament.

Injury to the anterior talofibular ligament (ATFL) is a common acute injury of the lateral foot ligament. Untimely and improper treatment significantly affects the quality of life and rehabilitation progress of patients. The purpose of this paper is to review the anatomy and the current methods of diagnosis and treatment of acute injury to the ATFL. The clinical manifestations of acute injury to the ATFL include pain, swelling, and dysfunction. At present, non-surgical treatment is the first choice for acute injury of the ATFL. The standard treatment strategy involves the "peace and love" principle. After initial treatment in the acute phase, personalized rehabilitation training programs can be followed. These may involve proprioception training, muscle training, and functional exercise to restore limb coordination and muscle strength. Static stretching and other techniques to loosen joints, acupuncture, moxibustion massage, and other traditional medical treatments can relieve pain, restore range of motion, and prevent joint stiffness. If the non-surgical treatment is not ideal or fails, surgical treatment is feasible. Currently, arthroscopic anatomical repair or anatomical reconstruction surgery is commonly used in clinical practice. Although open Broström surgery provides good results, the modified arthroscopic Broström surgery has many advantages, such as less trauma, rapid pain relief, rapid postoperative recovery, and fewer complications, and is more popular with patients. In general, when treating acute injury to the ATFL, treatment management and methods should be timely and reasonably arranged according to the specific injury scenario and attention should be paid to the timely combination of multiple therapies to achieve the best treatment results.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. METHODS: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. RESULTS: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. CONCLUSION: BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study.

OBJECTIVE: Diminished ovarian reserve (DOR) can lead to early menopause, poor fecundity, and an increased risk of disorders such as osteoporosis, cardiovascular disease, and cognitive impairment, seriously affecting the physical and mental health of women. There is still no safe and effective strategy or method to combat DOR. We have developed a novel Chinese herbal formula, Tongji anti-ovarian aging 101 (TJAOA101), to treat DOR. However, its safety and efficacy need to be further validated. METHODS: In this prospective and pre-post clinical trial, 100 eligible patients aged 18-45 diagnosed with DOR will be recruited. All participants receive TJAOA101 twice a day for 3 months. Then, comparisons before and after treatment will be analyzed, and the outcomes, including anti-mullerian hormone (AMH) and follicle-stimulating hormone (FSH) levels and the antral follicle count (AFC), the recovery rate of menopause, and the Kupperman index (KMI), will be assessed at baseline, every month during medication (the intervention period), and 1, 3 months after medication (the follow-up period). Assessments for adverse events will be performed during the intervention and follow-up periods. CONCLUSION: A multicenter, prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Genome-wide identification and characterization of PIN-FORMED (PIN) and PIN-LIKES (PILS) gene family reveals their role in adventitious root development in tea nodal cutting (Camellia Sinensis).

Auxin affects all aspects of plant growth and development, including morphogenesis and adaptive responses. Auxin transmembrane transport is promoted by PIN formation (PIN) and a structurally similar PIN-like (PILS) gene family, which jointly controls the directional transport of the auxin between plant cells, and the accumulation of intracellular auxin. At present, there is no study investigating the roles of CslPIN and CslPILS gene family in root development in the tea plant (Camellia sinensis). In this study, 8 CslPIN and 10 CslPILS genes were identified in the tea plant, and their evolutionary relationships, physical and chemical properties, conserved motifs, cis-acting elements, chromosome location, collinearity, and expression characteristics were analyzed. The mechanism of CslPIN and CslPILS in the formation of tea adventitious roots (ARs) was studied by the AR induction system. Through functional verification, the regulation of CslPIN3 gene on root growth and development of tea plant was studied by over-expression of CslPIN3 in Arabidopsis thaliana and in situ hybridization in Camellia sinensis. The results confirmed CslPIN3 was involved in the regulation of root growth and development as well as auxin accumulation. This study provides a better insight into the regulatory mechanism of CslPIN and CslPILS gene family on the formation of AR in tea plant.

Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

Racemic norneolignans from the resin of Ferula sinkiangensis and their COX-2 inhibitory activity.

Five new norneolignans sinkianlignans G-K (1-5), one phenolic compound ferulagenol A (6) and seven known compounds (7-13) were isolated from Ferula sinkiangensis. All the norneolignans were racemic mixtures, and chiral HPLC was used to further separate them. Their structures were assigned, including absolute configurations, using spectroscopic and computational methods. Biological evaluation showed that compounds 1-9 had significant COX-2 inhibitory activity with IC50 values ranging from 3.00 µM to 23.19 µM.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Dietary Supplement Intake and Fecundability in a Singapore Preconception Cohort Study.

Subfertility is a global problem affecting millions worldwide, with declining total fertility rates. Preconception dietary supplementation may improve fecundability, but the magnitude of impact remains unclear. This prospective cohort study aimed to examine the association of preconception micronutrient supplements with fecundability, measured by time to pregnancy (TTP). The study was conducted at KK Women's and Children's Hospital, Singapore, between February 2015 and October 2017, on 908 women aged 18-45 years old, who were trying to conceive and were enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). Baseline sociodemographic characteristics and supplement intake were collected through face-to-face interviews. The fecundability ratio (FR) was estimated using discrete-time proportional hazard modelling. Adjusting for potentially confounding variables, folic acid (FA) (FR 1.26, 95% confidence interval 1.03-1.56) and iodine (1.28, 1.00-1.65) supplement users had higher fecundability compared to non-users. Conversely, evening primrose oil supplement users had lower fecundability (0.56, 0.31-0.99) than non-users. In this study, preconception FA and iodine supplementation were associated with shortened TTP, while evening primrose oil use was associated with longer TTP. Nonetheless, the association between supplement use and the magnitude of fecundability changes will need to be further confirmed with well-designed randomised controlled trials.

Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Antiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. AIM OF THE STUDY: To observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. METHODS: An open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). RESULTS: Fibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. CONCLUSIONS: The combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated.

Unusual sesquilignans with anti-inflammatory activities from the resin of Ferula sinkiangensis.

Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.

Effects of Motherwort Injection Versus Intramuscular Oxytocin for Preventing Postpartum Hemorrhage Among Women Who Underwent Cesarean Section.

Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.

Impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis.

BACKGROUND: Fuzheng Huayu tablet is a traditional Chinese medicine (TCM) used for the treatment of liver fibrosis and cirrhosis. However, whether the combination with Fuzheng Huayu tablet could affect the antiviral efficacy of nucleos(t)ide remains a concern. The objective of this trial was to explore the impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis. METHODS: A prospective, randomized control trial was conducted. Patients with compensated hepatitis B cirrhosis were randomly divided into the treatment group (entecavir capsule plus Fuzheng Huayu tablet) and the control group (entecavir capsule plus simulant of Fuzheng Huayu), and followed up for 48 weeks. The dynamic changes of HBV DNA load, the rate of serological conversion of HBeAg, liver function, renal function and liver stiffness measurement (LSM) were monitored. The general clinical data and adverse events were also recorded. RESULTS: There was no significant difference in the rate of virological response and cumulative virological response between the treatment group and the control group (P > 0.05). After 48 weeks of treatment, the HBeAg seroconversion rate, biochemical response rate and LSM value were 21.05% and 4.76% (P = 0.164), 86.96% and 65.96% (P = 0.017), 9.5 kpa and 10.6 kpa (P = 0.827) in the treatment group and the control group, respectively. No serious adverse events related to the study therapy occurred during the trial. CONCLUSIONS: The antiviral entecavir combined with Fuzheng Huayu tablet did not affect the antiviral efficacy of entecavir, but could improve the rate of biochemical response, and had a tendency to improve the rate of serological conversion of HBeAg and liver fibrosis in patients with hepatitis B cirrhosis. Fuzheng Huayu tablet is clinically safe for patients with hepatitis B cirrhosis.

Regioisomers Salviprolin A and B, Unprecedented Rosmarinic Acid Conjugated Dinorditerpenoids from Salvia przewalskii Maxim.

Salvia przewalskii Maxim is a perennial plant from the genus Salvia (family Lamiaceae). The roots of S. przewalskii were long used as a traditional herb to treat blood circulation related illnesses in China. As part of our continuing interest in polycyclic natural products from medicinal plants, two unprecedented adducts comprised of a dinor-diterpenoid and a 9'-nor-rosmarinic acid derivative, linked by a 1,4-benzodioxane motif (1 and 2), were isolated from the roots of S. przewalskii. Their structures were established by extensive spectroscopic approaches including 1D, 2D NMR, and HRFABMS. Their cytotoxic activities against five human tumor cell lines were evaluated.

HA targeted-biodegradable nanocomposites responsive to endogenous and exogenous stimulation for multimodal imaging and chemo-/photothermal therapy.

Multimodal imaging-guided accurate tumor-targeting and efficient synergistic therapy are of great importance for cancer therapy in vitro and in vivo. In this study, a biocompatible, tumor-targeted, on-demand chemo-/photothermal therapeutic nanoplatform (HIDSiGdNPs@PDA-HA) based on hollow mesoporous organic silica nanoparticles (HMONs) was used for bimodal imaging and multi-factor stepwise response for drug release and treatment. Targeted molecule hyaluronic acid (HA) promoted the endocytosis of HIDSiGdNPs@PDA-HA in HeLa cancer cells. The gatekeeper pH-/light-sensitive PDA coating was stimulated by the endogenous tumor acidic microenvironment and exogenous NIR laser to release doxorubicin (DOX). Thereafter, HMONs containing S-S bonds were reduced and degraded by endogenous glutathione (GSH), and the drug was further released rapidly to kill cancer cells. Importantly, the photothermal reagent indocyanine green (ICG) was always retained in the carrier, improving the effectiveness of photothermal therapy. The loaded Gd-doped silicon nanoparticles (SiGdNPs) combined with DOX and ICG led to multi-color fluorescence imaging in vitro and magnetic resonance imaging in vivo to realize targeted diagnosis and track drug distribution. The treatment results of tumor-bearing mice also proved the excellent synergistic therapy. It is believed that the multifunctional nanomaterials with dual mode imaging capability and targeted and controlled collaborative therapy would provide an alternative for accurate diagnosis and efficient treatment.

Pharmacological effects and mechanisms of muscone.

Musk, the dried secretion from the preputial follicles of the male musk deer (genus Moschus), possesses various pharmacological activities and has been used extensively in traditional Chinese medicine for thousands of years. Muscone is the main active ingredient of musk and exerts pharmacological effects similar to those of musk. Although muscone was notably used to treat various disorders and diseases, such as neurological disorders, chronic inflammation and ischemia-reperfusion injury, most of the mechanisms of the pharmacological action of muscone remain unclear because of slow progress in research before the 21st century. In recent years, the pharmacological activities and mechanisms of muscone have been clarified. The present article summarizes the pharmacological and biological studies on cerebrovascular disease, cardiovascular disease, neurological effects, cancer and others and the associated mechanisms of the action of muscone to date.

[Influence of acupuncture plus moxibustion on changes of synaptic structure and expression of synaptic skeleton related genes and proteins in prefrontal cortex of heroin re-addicted rats].

OBJECTIVE: To observe the effect of acupuncture plus moxibustion on the synaptic ultrastructure and expression of synaptic skeleton related proteins in the prefrontal cortex (PFC) of heroin re-addicted rats, so as to reveal its mechanisms underlying improvement of heroin addiction. METHODS: Twenty-four Wister rats (half male and half female) were randomly divi-ded into normal control, model and acupuncture groups (n＝8 in each group). The heroin re-addicted model was established by muscular injection of heroin into the hind limbs for 8 days (incremental 0.8-3.6 mg, once daily for 6 days, and twice daily for 2 days), followed by conventional breeding for 5 days (detoxification), the procedure (addition－detoxification) was repeated 3 cycles. For rats of the acupuncture group, "Baihui" (GV20) was needled with filiform needles which were retained for 30 min, and moxibustion was then applied to bilateral "Shenshu" (BL23) for 30 min. The treatment was conducted once daily during the deto-xification. On the 39th day of experiment, the bilateral prefrontal cortex tissues were sampled for examining the ultrastructure by using transmission electron microscope (TEM) after fixative solution immersion and for determining the expression of genes and proteins of activity-regulated cytoskeleton-associated protein (Arc), microtubule-asso-ciated protein-2 (MAP-2) and microtubule-associated protein Tau (Tau) with quantitative real-time PCR and Western blot, respectively. RESULTS: After modeling, the expression levels of Arc mRNA and protein were significantly up-regulated, and those of MAP-2 and Tau mRNA and proteins ob-viously down-regulated in the model group relevant to the normal control group (P<0.05). Following the intervention, the up-regulated Arc protein and mRNA and the down-regulated MAP-2 and Tau were obviously reversed relevant to the model group (P<0.05). Outcomes of TEM showed unclear pre- and post-membranes of the synapses, narrowing of the synaptic gap and non-uniform of the density of the thickened dense plaque after modeling, which was relatively milder in the acupuncture group. CONCLUSION: Acupuncture plus moxibustion can improve changes of synaptic ultrastructure in heroin re-addicted rats, which may be related to their effect in regulating the expression of some synaptic skeleton proteins and genes.

[Process optimization for extraction and purification of polysaccharides from Cistanche deserticola].

In this study, taking Cistanche deserticola in Xinjiang as the experimental material, the optimal process for extracting polysaccharides from C. deserticola with water extraction was studied by using single factor and orthogonal experiment. Its effects on protein removal and polysaccharides retaining were investigated by using Sevag, enzymatic method or combination of these two methods, so as to determine the optimal method for protein removal from polysaccharides of C. deserticola; the decolorization and purification methods such as macroporous resin of AB-8 and activated Carbon were used to determine the optimal process. The results showed that the extraction rate of polysaccharides from C. deserticola was 18.40% during the optimal process of the water extraction as follows: extraction temperature 75 ℃, extraction time 165 min and solid-liquid ratio 1∶55. The protein removal rate can reach 31.40% and polysaccharide retention rate can reach 96.00% under the optimal protein removal process: temperature 50 ℃, time 2 h, and papain dosage 0.2%. The decolorization rate of activated Carbon and macroporous resin called AB-8 was 80.37% and 86.43%, and the recovery rate of polysaccharides was 77.05% and 91.93%, respectively, suggesting that macroporous resin was more suitable for decoloration. Macroporous resin named AB-8 increased the purity of the polysaccharide crude extract from 67.70% to 84.80% under the following conditions: concentration of the sample 4 g·L~(-1), concentration of the eluent 60% ethanol, and the flow rate 1 mL·min~(-1), showing significant purification effect.