Root colonization by beneficial rhizobacteria.

Rhizosphere microbes play critical roles for plant's growth and health. Among them, the beneficial rhizobacteria have the potential to be developed as the biofertilizer or bioinoculants for sustaining the agricultural development. The efficient rhizosphere colonization of these rhizobacteria is a prerequisite for exerting their plant beneficial functions, but the colonizing process and underlying mechanisms have not been thoroughly reviewed, especially for the nonsymbiotic beneficial rhizobacteria. This review systematically analyzed the root colonizing process of the nonsymbiotic rhizobacteria and compared it with that of the symbiotic and pathogenic bacteria. This review also highlighted the approaches to improve the root colonization efficiency and proposed to study the rhizobacterial colonization from a holistic perspective of the rhizosphere microbiome under more natural conditions.

Genetic characterization of HIV-1 viruses among cases with antiretroviral therapy failure in Suzhou City, China.

BACKGROUND: This retrospective study aimed to characterize the distribution of HIV-1 genotypes and the prevalence of drug resistance mutations in people with antiretroviral treatment (ART) failure in Suzhou City, China. METHODS: Pol gene of HIV-1 viruses in blood samples of EDTA anticoagulants from 398 patients with failed antiviral treatment was successfully amplified by using an in-house assay. Drug resistance mutations were analyzed by using the Stanford HIV Drug Resistance Database system ( https://hivdb.stanford.edu/hivdb/by-mutations/ ). HIV-1 genotypes were determined by the REGA HIV subtyping tool (version 3.46, https://www.genomedetective.com/app/typingtool/hiv ). Near full-length genomes (NFLG) of HIV-1 viruses were obtained by next generation sequencing method. RESULTS: Sequences analysis of the pol gene revealed that CRF 01_AE (57.29%, 228/398) was the dominant subtype circulating in Suzhou City, followed by CRF 07_BC (17.34%, 69/398), subtype B (7.54%, 30/398), CRF 08_BC (6.53%, 26/398), CRF 67_01B (3.02%, 12/398) and CRF55_01B (2.51%, 10/398). The overall prevalence of drug-resistant mutations in cases with ART failure was 64.57% (257/398), including 45.48% (181/398) for nucleotide reverse transcriptase inhibitors (NRTIs) mutations, 63.32% (252/398) for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations, and 3.02% (12/398) for protease inhibitors (PIs) mutations. Ten near full-length genomes (NFLG) of HIV-1 viruses were identified, including six recombinants of CRF 01_AE and subtype B, two recombinants of CRF 01_AE, subtype B and subtype C sequences, one recombinant of CRF 01_AE and subtype C and one recombinant of CRF 01_AE, subtype A1 and subtype C. CONCLUSIONS: The high prevalence of drug-resistant HIV-1 viruses was a serious challenge for HIV prevention and treatment of people with HIV infection. Treatment regimens for ART failure patients should be adjusted over time based on the outcome of drug resistance tests. NFLG sequencing facilitates the identification of new recombinants of HIV-1.

Sacral neuromodulation for overactive bladder using the InterStim and BetterStim systems.

This study aimed to evaluate differences in the clinical outcomes of different sacral neuromodulation systems (InterStim and BetterStim) used in the treatment of overactive bladder. Data from a previously established database of sacral neuromodulation in China (the InterStim system) and a 2020 clinical trial of the BetterStim system were screened. Patients with overactive bladder undergoing stage II implanted pulse generator implantation were selected for analysis and divided into InterStim and BetterStim system groups. Voiding diaries and subjective scores obtained preoperatively, after stage I tined-lead implantation (experience period), and after stage II implanted pulse generator implantation were compared between the two groups. This study included 113 patients with overactive bladder (43, InterStim system group; 70, BetterStim system group). Voiding diaries and subjective scores significantly improved in both the InterStim and BetterStim system groups over the treatment period. Specifically, the urination frequency (all P < 0.001), average voiding volume (all P < 0.001), and average urinary leakage (InterStim, P < 0.05; BetterStim, P < 0.01) in both groups significantly improved at different periods during treatment. At the same time, the urgency perception scale (P < 0.001) and OAB-related quality of life score (InterStim, P < 0.05; BetterStim, P < 0.01) also significantly improved. There was no significant difference in urination frequency at baseline between the two groups (P = 0.169). Urination frequency was significantly higher in the BetterStim system group than in the InterStim group during the experience period and at follow-up (P = 0.031, P = 0.006). There was no significant difference in the number of urinary leakages between the different systems at baseline (P = 0.662), although this was higher in the InterStim system group during the experience period (P = 0.016), and the difference disappeared at the last follow-up (P = 0.565). There were significant differences in baseline urgency perception scale (P = 0.001) and OAB-related quality of life score (P < 0.001) between the two groups; however, these differences were not maintained at follow-up (P = 0.81, P = 0.479). Both sacral neuromodulation systems are safe and effective in treating overactive bladder. The InterStim system may be more beneficial for patients with dry overactive bladder. Satisfactory outcomes may be achieved with the BetterStim system in patients with wet overactive bladder. However, further studies are required to confirm this finding.

Sacral Neuromodulation in Patients With Neurogenic Lower Urinary Tract Dysfunction: A Multicenter Retrospective Study From China.

OBJECTIVES: This retrospective study aimed to determine the effectiveness of sacral neuromodulation (SNM) on neurogenic lower urinary tract dysfunction (NLUTD) and analyze the predictive factors. MATERIALS AND METHODS: From January 2012 to January 2020, 152 subjects with NLUTD from four medical centers in China received SNM test stimulation. Subjects were assessed via bladder diaries, postvoid residual volumes (PRVs) and neurogenic bowel dysfunction (NBD) scores before and during the testing period. Patients who showed a minimum 50% improvement in symptoms through the SNM test phase were eligible for permanent SNM implantation. RESULTS: The pooled success rate for chronic urinary retention was 31.0% (40/129), which was significantly lower (p < 0.05) than the rates for frequency-urgency (64.8%, 59/91), urinary incontinence (65.2%, 30/46), and NBD score (61.7%, 82/133). The results of the risk factor analysis showed that the urinary storage symptom was a statistically significant positive predictor (p = 0.001). CONCLUSIONS: In conclusion, SNM is an effective and reliable method for treating NLUTD, especially in patients with urinary storage symptoms. Although not all of the symptoms in every patient can be resolve, SNM still might be a superior choice together with other treatment procedures.

Influence of patient sex on the effectiveness of sacral neuromodulation: A cohort study from China.

BACKGROUND: Sacral neuromodulation (SNM) has been widely used to treat lower urinary tract dysfunction. Studies have shown a higher conversion rate among female patients than among male patients. However, the influence of gender on the clinical effectiveness of SNM remains unclear. We aimed to confirm whether patients of both genders show similar benefits after SNM treatment. MATERIALS AND METHODS: Clinical data of patients with lower urinary tract symptoms associated with pelvic floor dysfunction (overactive bladder, neurogenic bladder, interstitial cystitis/painful bladder syndrome, idiopathic urinary retention) treated with SNM in 10 medical centres in China between January 2012 and December 2016 were retrospectively collected. The patients were classified by gender. Variations in objective (voiding diary) and subjective scores in the baseline, testing, and last follow-up periods were compared. Data were analysed using statistical measures. RESULTS: The study included 203 patients (93 males, 110 females). There were no statistical differences in baseline information between the two groups, both groups showed improvement over time. Unsatisfactory improvement was observed in the quality of life and sexual life scores of both groups over the entire treatment period (all p＞0.05). Although there was a difference in the maximum voiding volume between the groups at baseline, no difference was observed at the last follow-up (p = 0.004, p = 0.044, p = 0.124), unlike in the average volume where a difference was noted at the last follow-up (p = 0.085, p = 0.964, p = 0.031). While there were no differences in quality of life, sexual life, or pelvic pain and urinary urgency frequency scores at baseline, a significant difference was observed at the last follow-up, and the degree of improvement was less among female patients (p = 0.836, p = 0.131, p = 0.015; p = 0.294, p = 0.265, p = 0.013; p = 0.299, p = 0.087, p = 0.015). CONCLUSION: SNM treatment elicited a similar effect on patients of both gender; however, a significant difference was observed regarding patient satisfaction with the treatment. Further preoperative patient education, especially, for female patients with interstitial cystitis/painful bladder syndrome may improve patient satisfaction.

Ginkgolide B inhibits hydrogen peroxide­induced apoptosis and attenuates cytotoxicity via activating the PI3K/Akt/mTOR signaling pathway in H9c2 cells.

Ginkgolide B (GB) is a diterpene lactone found in the leaves of the traditional Chinese medicinal plant Ginkgo that has been shown to have various pharmacological effects. However, the anti­apoptotic properties of GB in cardiovascular disease remain poorly understood. The present study aimed to investigate the effect of GB on hydrogen peroxide­induced cell injury in cardiac H9c2 cells, and to further clarify its protective mechanism of action. An in vitro hydrogen peroxide­treated H9c2 cell model was used in order to mimic myocardial ischemia­reperfusion (I/R) injury. Cell viability was assessed by the Cell Counting Kit­8 assay. The induction of apoptosis was determined by flow cytometry and staining was performed using Hoechst 33342. In addition, the effect of GB on the expression levels of apoptosis­associated proteins was evaluated by western blot analysis. The present study demonstrated that GB protected against hydrogen peroxide­induced cytotoxicity and cell apoptosis in H9c2 cardiac cells. GB upregulated the expression level of the anti­apoptotic protein Bcl­2 and downregulated the expression levels of the pro­apoptotic proteins cleaved caspase­3 and Bax in hydrogen peroxide­treated H9c2 cells. The molecular mechanism underlying the anti­apoptotic effects of GB was subsequently detected. GB pretreatment activated the PI3K/Akt/mTOR signaling pathway and caused an increase in the phosphorylation levels of Akt and mTOR in hydrogen peroxide­treated H9c2 cells. These results revealed that GB inhibited hydrogen peroxide­induced apoptosis in H9c2 cells via activation of the PI3K/Akt/mTOR signaling pathway. These findings indicate the potential therapeutic benefits of GB in the treatment of myocardial I/R injury.

The effects of refractory pollutants in swine wastewater on the growth of Scenedesmus sp. with biofilm attached culture.

Microalgae have been widely used for treatment of swine wastewater. However, the research on combined treatment of refractory pollutants ammonia nitrogen, Cu (II) and antibiotics from swine wastewater was still scattered. This study, the growth and removal efficiency of NH4Cl, CuSO4, tetracycline, norfloxacin and sulfadimidine with selected Scenedsmus sp. was investigated by biofilm attached culture. The results showed that low concentration of ammonia nitrogen had little effect on algae growth. The highest biomass productivity was 6.2 g/(m2d) at the concentration of NH4Cl of 50.0 mg/L, which was similar to that of a standard growth medium BG 11. Cu (II) concentration of 1.0 mg/L could accelerate the growth of Scenedsmus sp., and the highest biomass was 57.2 g/m2 in 8 days. Moreover, the highest biomass mean values was 59.5 g/m2, 57.1 g/m2, and 58.1 g/m2, respectively, when tetracycline concentration was 20.0 mg/L, norfloxacin concentration was 100.0 mg/L and sulfadimidine concentration was 10.0 mg/L. The removal efficiency of ammonia nitrogen, copper, tetracycline, norfloxacin and sulfadimidine with Scenedsmus sp. at their optimal initial concentration by biofilm attached culture was 85.2%, 64.6%, 74.6%,71.2%, and 62.3%, respectively. This study provides a theoretical basis for the purification of refractory substances from swine wastewater.

Dual-Responsive Dual-Drug-Loaded Bioinspired Polydopamine Nanospheres as an Efficient Therapeutic Nanoplatform against Drug-Resistant Cancer Cells.

Multidrug resistance evoked by overusing pharmaceuticals of poor water solubility has posed a serious threat to public health, which urges the development of safe and efficacious therapeutic formulations. In this study, biomimetic nanospherical polydopamine (PDA) formed under mild conditions was modified using methoxypolyethylene glycol amine (m-PEG-NH2) to produce a polydopamine-based drug delivery platform. As characterized by various physicochemical methods, the PEGylated PDA with a uniform size distribution showed superior biocompatibility and efficient load capability for two hydrophobic anticancer drugs of paclitaxel and phytochemical curcumin, which exhibited synergistic cytotoxicity and a pH/ROS-responsive release behavior. Significantly, an enhanced effect of the encapsulated paclitaxel and curcumin was identified toward the drug-resistant A549/TAX cancer cells, which was correlated with the improved cellular internalization of hyperbranched PDA composites and distinctive cell cycle arrest of loaded drugs. The dual-drug-loaded spherical PDA nanocomposites hold enormous potential to tackle drug resistance from a chemotherapy perspective.

Molecular cloning and phenotypic analysis of drug-resistance mutants with relevant S-region variants of HBV for a patient during 189-month anti-HBV treatment.

BACKGROUND: A unique chronic hepatitis B patient was followed over 189 months of nucleoside/nucleotide analogue (NA) therapies with the analysis of multiple drug-resistance HBV mutants. METHODS: Clonal sequencing (≥20 clones/sample) was performed on sera sampled at 41 time points, and the phenotypic features of eight representative mutants were analysed. RESULTS: Lamivudine (LAM)-, adefovir dipivoxil (ADV)-, entecavir (ETV)- and repeat ADV-resistance mutants emerged upon individual sequential NA monotherapy. The efficacy of NA combination rescue therapies ranked as LAM+ADV < ETV+ADV < ETV+ tenofovir disoproxil fumarate (TDF). Specifically, LAM+ADV and ETV+ADV suppressed viral loads to <100 IU/ml for a long period of time, either with or without late stage HBV DNA fluctuations. Furthermore, ETV+TDF suppressed the viral load to <10 IU/ml. During the LAM+ADV and ETV+ADV combination therapies, ETV-resistance mutants dominated at most time points, and multidrug-resistance (MDR) mutants that harboured LAM-, ETV- and ADV-resistance mutations were intermittently detected. Interestingly, the rtA181T-causative sW172stop to sW172non-stop mutation transition was observed at HBV DNA fluctuations. In a phenotypic analysis, two MDR strains had cross-resistance to LAM, ETV and ADV, and a lower susceptibility to TDF (<10-fold decrease compared with the wild-type strain). In contrast, the natural replication capacity was inversely associated with the number of primary resistant mutations which would limit MDR mutant development. CONCLUSIONS: Taken together, viral drug susceptibility, replication capacity, and perhaps immunological adaptation may play coordinated roles in the fitness of drug-resistance mutants. ETV+TDF therapy is the preferred option for treating chronic hepatitis B patients with multiple drug failure.

Remotely programmed sacral neuromodulation for the treatment of patients with refractory overactive bladder: a prospective randomized controlled trial evaluating the safety and efficacy of a novel sacral neuromodulation device.

PURPOSE: The efficacy and safety of a novel remotely programmed BetterStim sacral neuromodulation (SNM) system was evaluated in patients with refractory overactive bladder (OAB) in a prospective, controlled, multicenter trial. METHODS: A total of 84 patients referred for SNM therapy from October 2015 to January 2018 were studied. Of the patients who qualified for implantation, 37 and 33 were randomly assigned to treatment and control groups, respectively. Patients in the treatment group underwent stimulation upon implantation, while stimulation was delayed in the control group for 3 months. Follow-up visits, consisting of voiding diary outcome, questionnaires regarding overactive bladder symptom score (OABSS) and quality of life were conducted at 1, 3, and 6-month post-implantation. RESULTS: Compared with the control group, subjects in the treatment group exhibited statistically significant improvement in OAB symptoms at 3 months. The overall success rate was achieved in 72% of the treatment group, compared with 12% of the control group at 3 months. At 6 months, there were no significant differences in key voiding diary variables between the two groups. Further, this study demonstrated sustained improvement in urinary symptom interference in OAB patients. In addition, nearly all patients expressed great satisfaction with the remote-programming methods. No serious adverse events occurred, and device-related adverse events rate was 12.86%. CONCLUSION: This clinical study demonstrates subjective and objective success of the BetterStim SNM system. Importantly, our data suggest that remote programming can be safely used as a viable option for the conventional programming with a high degree of patient satisfaction.

Protective effects of sodium tanshinone IIA sulfonate on cardiac function after myocardial infarction in mice.

Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, has been used in traditional Chinese medicine for many years. Many experiments have demonstrated that STS has anti-inflammatory, anti-apoptosis and angiogenesis effects. However, it is unclear whether STS has the same beneficial effects on myocardial infarction in vivo. The aim of our experiments was to investigate whether STS could improve cardiac function and prevent myocardial remodeling after myocardial infarction (MI) in mice. The MI model was established by surgical ligation of the left anterior descending (LAD) coronary artery. Then the mice were randomly divided into STS and untreated groups. The results of treatment for 3 weeks showed that STS could increase the survival rate, reduce the release of some inflammatory cytokines, inhibit cell apoptosis and promote angiogenesis. The study presents a new potential treatment method for ischemic heart disease.

Results of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Five-Year Experience of a Retrospective, Multicenter Study in China.

PURPOSE: This five-year, retrospective, multicenter study evaluated the long-term safety and efficiency of sacral neuromodulation (SNM) in Chinese patients with urinary voiding dysfunction. PATIENTS AND METHODS: This is a Chinese national, multicenter, retrospective study that included 247 patients (51.2% female) who received an implantable pulse generator (IPG) (InterStim, Medtronic, Minneapolis, MN, USA) between 2012 and 2016. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline. The results were further stratified by identifying patients who showed >50% improvement and those although showed <50% improvement but still wanted to receive IPG; these data were collected and analyzed for general improvement. RESULTS: Following test stimulation, 187 patients (43%) declined implantation and 247 (57%) underwent implantation using InterStim®. Among 247 patients, 34 (13.7%) had overactive bladder (OAB), 59 (23.8%) had interstitial cystitis/bladder pain syndrome (IC/BPS), 47 (19%) had idiopathic urinary retention (IUR), and 107 (44.1%) had neurogenic bladder (NB). IPG efficiency rate for OAB, interstitial cystitis/bladder pain syndrome, idiopathic urinary retention, and neurogenic bladder were 42.5, 72.4, 51.6, and 58.8%, respectively. The mean duration of follow-up was 20.1 ± 12.8 months. CONCLUSIONS: SNM appears effective in the long term, with a total IPG implantation rate of approximately 57% (ranging between 42.5 and 72.4% depending on indication). Interstitial cystitis/bladder pain syndrome appear to be the best indication for stage I testing. Chinese neurogenic bladder patients are most inclined to choose SNM. SNM is relatively safe, with low postoperation adverse events of 16.1% and reoperation rate of 3.2% during the follow-up period.

Chinese herbal extract Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant hepatitis B virus (HBV) in vitro and effectively suppressed HBV replication in mouse model.

This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 µg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2.A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Su-duxing and entecavir combination showed a better anti-HBV effect than each single of agents. Mice treated with Su-duxing (45.0 mg kg-1 d-1 for 2 weeks) had 1.39 log10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Quantitative RT-PCR verified that CCNA2, ATF4, FAS and CDKN1A expression levels had significant difference between Su-duxing-treated and control groups. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition.

[Efficacy of Huang'e Capsules on benign prostatic hyperplasia with Qi-deficiency, blood stasis and damp heat block: A stratified analysis].

OBJECTIVE: To evaluate the efficacy and safety of Huang'e Capsules in the treatment of BPH with Qi-deficiency, blood stasis and damp heat block. METHODS: This study included 1 456 cases of BPH with Qi-deficiency, blood stasis and damp heat block from 40 hospitals of Zhejiang and Anhui Provinces between June 2014 and July 2017. The patients were aged 40－85 years and treated with Huang'e Capsules at a dose of 4 capsules, tid, for a course of 6 weeks. The IPSSs of the patients were obtained before and after 2, 4 and 6 weeks of medication, and a stratified analysis was made on the factors influencing the therapeutic effects, such as age, the stage of BPH, and concomitant medication of urogenital and reproductive hormone drugs. RESULTS: After 6 weeks of medication, the IPSS of the patients was decreased by 8.4 ± 5.4 (ï¼»42.9 ± 22.7ï¼½ %) as compared with the baseline (19.2 ± 6.8) (P < 0.05), with a total effectiveness rate of 71.9% and an excellence rate of 23.1%. After 6 weeks of medication, the IPSSs of the patients with stage-Ⅰ, -Ⅱ and -Ⅲ BPH were decreased by 7.3 ± 6.8, 6.6 ± 4.3 and 11.0 ± 5.5, with total effective rates of 69.5%, 70.1% and 74.7%, respectively, with statistically significant differences among the three stages (P < 0.05), and so were those in the patients aged ≤50 years (by 7.4 ± 5.8), 51－60 years (by 7.9 ± 5.3), 61－70 years (by 8.7 ± 5.6) and >70 years (by 8.6 ± 5.1), but with no statistically significant differences among different age groups (P > 0.05). At 6 weeks, the IPSS was reduced by 7.1 ± 5.9 by concomitant medication of urogenital and reproductive hormone drugs, 8.7 ± 5.4 by concomitant medication of other drugs, and 8.4 ± 5.3 by non-concomitant medication, with no statistically significant differences among the three types of medication (P > 0.05). CONCLUSIONS: Huang'e Capsules can evidently improve the symptoms of BPH, with the best effect on stage-Ⅲ BPH, and the effect does not differ significantly with age or drug concomitance.

[Hypospadias induced by maternal exposure to di-n-butyl phthalate and its mechanisms in male rat offspring , , , , ,].

OBJECTIVE: To induce hypospadias in male rat offspring by maternal exposure to di-n-butyl phthalate (DBP) during late pregnancy and further investigate its mechanisms. METHODS: We randomly divided 20 pregnant rats into a DBP exposure and a control group, the former treated intragastrically with DBP while the latter with soybean oil at 750 mg per kilogram of the body weight per day from gestation days (GD) 14 to 18. On postnatal day (PND) 1, we recorded the incidence rate of hypospadias and observed the histopathological changes in the genital tubercle of the hypospadiac rats. We also measured the level of serum testosterone (T) by radioimmunoassay and determined the mRNA and protein expressions of the androgen receptor (AR), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4) and fibroblast growth factor 8 (Fgf8) in the genital tubercle by real-time PCR and Western blot. RESULTS: No hypospadiac male rats were found in the control group. The incidence rate of hypospadias in male offspring was 43.6% in the DBP-treatment group. Histological analysis confirmed hypospadiac malformation. The serum testosterone concentration was decreased in the hypospadiac male rats as compared with the controls (ï¼»0.49 ± 0.05ï¼½ vs ï¼»1.12 ± 0.05ï¼½ ng/ml, P <0.05). The mRNA expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle were significantly lower in the hypospadiac male rats than in the controls (AR: 0.50 ± 0.05 vs 1.00 ± 0.12, P <0.05; Shh: 0.65 ± 0.07 vs 1.00 ± 0.15, P <0.05; Bmp4: 0.42 ± 0.05 vs 1.00 ± 0.13, P <0.05; Fgf8: 0.46 ± 0.04 vs 1.00 ± 0.12, P <0.05), and so were their protein expressions (AR: 0.34 ± 0.05 vs 1.00 ± 0.09, P <0.05; Shh: 0.51 ± 0.07 vs 1.00 ± 0.12, P <0.05; Bmp4: 0.43 ± 0.05 vs 1.00 ± 0.11, P <0.05; Fgf8: 0.57 ± 0.04 vs 1.00 ± 0.13, P <0.05). CONCLUSIONS: Maternal exposure to DBP during late pregnancy can induce hypospadias in the male rat offspring. DBP affects the development of the genital tubercle by reducing the serum T concentration and expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle, which might underlie the mechanism of DBP inducing hypospadias.

Increased occurrence of mutant rtI233V of HBV in patients receiving adefovir therapy.

BACKGROUND: The study aimed to clarify whether the rtI233V substitution affects adefovir (ADV) resistance. METHODS: A total of 18,419 patients from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of the polymerase was screened by direct sequencing and verified by clonal sequencing if necessary. Replication-competent wild-type and mutant HBV genomic amplicons were transfected into HepG2 cells for phenotypic analysis of viral replication capacity and drug susceptibility. RESULTS: The rtI233V substitution was detected in 38/5,344 (0.71%) ADV-treated patients and in 8/13,075 patients without receiving ADV (P<0.001). Eight patients with rtI233V ± rtA181V/rtN236T had virological breakthrough in the clinical course of ADV treatment. Phenotypic analysis showed that rtI233V mutants from patient 1 and patient 2 exhibited 1.57-fold and 1.51-fold decreased susceptibility to ADV, respectively, compared to wild-type virus; by contrast, rtN236T and rtI233V+N236T mutants from patient 1 had 6.82-fold and 5.28-fold decreased susceptibility to ADV. rtI233V, rtN236T and rtI233V+N236T mutants had 97.5%, 30.2% and 69.7% of replication capacity compared to wild-type virus in the absence of antivirals and all remained susceptible to lamivudine, entecavir and tenofovir. Viral replication capacity correspondingly decreased after eliminating rtI233V from rtI233V+N236T mutant and was restored after introducing rtI233V into rtN236T mutant. In clinical practice, switching to entecavir rescue therapy suppressed HBV DNA to an undetectable level for both patients. CONCLUSIONS: rtI233V usually emerged in ADV-treated patients with little impact on ADV susceptibility but it effectively restored replication capacity of the rtN236T mutant, suggesting that rtI233V may partly serve as a compensatory mutation associated with ADV resistance.

Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.

The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.

Beneficial effects of ginsenoside-Rg1 on ischemia-induced angiogenesis in diabetic mice.

Neovascularization and the formation of collateral vessels are often impaired in diabetes mellitus (DM) population compared with non-diabetics. Alterations in vascular endothelial growth factor (VEGF) signaling and endothelial nitric oxide synthase (eNOS) dysfunction have been confirmed to play a crucial role in impaired neovascularization in diabetic mice. Accumulating data have suggested that Rg1, a main component of Panax ginseng, has the ability to promote tubulogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, and that the mechanism involves increased expression level of VEGF as well as increased eNOS activation. Thus, we speculated that Rg1 might also have therapeutic effects on the impairment of neovascularization in diabetic individuals. The aim of the present study was to investigate whether Rg1 could improve angiogenesis in ischemic hindlimb of diabetic mice in vivo. Our data demonstrated that Rg1 treatment resulted in improved angiogenesis in the diabetic ischemic hindlimb, and the potential mechanism might involve increased eNOS activation, upregulated VEGF expression, and inhibited apoptosis. Our results suggest that Rg1 may be used as a novel and useful adjunctive drug for the therapy of peripheral arterial disease in DM.

[Determination of astragulin in Thesium chinese by RP-HPLC].

OBJECTIVE: To establish a determination method of astragulin in Thesium chinese. METHOD: RP-HPLC analytical method was established using a Polaris C18 column and acetonitrile-water (23:77) as the mobile phase, with a flow rate of 10 mL x min(-1), detected at 346 nm. The method of sample is refluxing exation by 50% alcohol for 2 times. RESULT: The content of astragulin was from 0. 120% to 0. 155%, in different groups of T. chinese collected from the same location. CONCLUSION: The method was validated to show convenient and reliable.