Throughout the guidelines for hypertension published in China and abroad in recent years, the therapeutic principles of hypertension drug treatment mainly include: hypotensive treatment was given according to the overall risk level of patients with hypertension. Intensive antihypertensive therapy should be adopted to achieve maximum cardiovascular benefits, if conditions permit. Comprehensive intervention is needed for factors other than blood pressure,including treatable risk factors, subclinical target organ damage, and a variety of co-existing clinical diseases.The optimized principles of antihypertensive therapy include initiation of combined drug in most patients to raise the rate of blood pressure treatment targets, and the single-pill combination is preferred in combination therapy.

Objective: To investigate the effects of dihydromyricetin on proliferation and apoptosis of human lung adenocarcinoma cell line NCI-H1975 in vitro, and to explore its molecular mechanism. Methods: After treatment with different concentrations of dihydromyricetin (10, 25, 50, 75 and 100 μmol/L) for different time (12, 24 and 48 h), the proliferation of human lung adenocarcinoma NCI-H1975 cells was detected by CCK-8 assay. The cell cycle and apoptosis rate of NCI-H1975 cells treated with different concentrations of dihydromyricetin (25, 50 and 100 μmol/L) for 24 h were determined by flow cytometry, and the change of cell morphology was observed by inverted phase contrast microscopy. Real-time fluorescent quantitative-PCR and Western blotting were used to analyze the expression levels of Bcl-2, Bax and Bad genes in NCI-H1975 cells treated with 25, 50 or 100 μmol/L dihydromyricetin for 24 h. Results: Dihydromyricetin significantly inhibited the proliferation of human lung adenocarcinoma NCI-H1975 cells in a dose- and time-dependent manner (P < 0.05). Dihydromyricetin significantly induced apoptosis of NCI-H1975 cells (P < 0.01), but it did not induce cell cycle arrest (P > 0.05). Furthermore, dihydromyricetin significantly decreased the expression levels of Bcl-2 mRNA and protein in NCI-H1975 cells (both P < 0.05), and up-regulated the expression levels of Bax mRNA and protein as well as the expression level of phospho-Bad protein (all P < 0.05), but did not change the expression levels of Bad mRNA and protein (both P > 0.05). Conclusion: Dihydromyricetin can suppress the growth of human lung adenocarcinoma cells through regulating the expression of Bcl-2 protein family in mitochondrial apoptotic pathway. Dihydromyricetin may be a potential drug for the treatment of lung carcinoma.

Objective To identify whether rtL180M+A186T+M204V mutation is a novel entecavir (ETV)-resistant mutation. Methods A total of 12 708 patients in the Fifth Medical Center of Chinese PLA General Hospital from July 2011 to July 2016 were enrolled in this study. Drug resistance mutation in reverse transcriptase region (RT) were analyzed by direct sequencing and verified by clonal sequencing if rtL180M+A186T+M204V has been detected (≥20 clones/sample); 1.1-mer HBV replicons harboring wild-type or mutant RT gene were constructed respectively and transfected into HepG2 cells for phenotypic analysis. Results ETV experienced patients were detected in 4047 of total patients. Among these patients, classical ETV-resistant mutation of HBV and rtL180M+A186T+M204V mutation were detected in 795(19.64%) and 7(0.17%), respectively. The rtL180M+A186T+M204V mutant was consistent with the features of ETV-resistant mutation: all the rtA186T-positive patients had a history of lamivudine exposure prior to ETV treatment; the emergence of the mutations was associated with virological breakthrough or inadequate virological response to ETV; phenotypic analysis showed that patient-derived rtL180M+A186T+M204V mutant exhibited 13.3% replication capacity and 210.2-fold decreased susceptibility to ETV compared to the wild-type strain, while the mutant remained sensitive to tenofovir (TDF). Conclusions rtL180M+A186T+M204V as a novel ETV-resistance mutation has a low clinical detection rate, which is related to the markedly reduced replication capacity of the mutant. TDF-based rescue therapy should be considered for patients harboring rtL180M+A186T+M204V mutation in clinical practice.

Objective To study the prescription and preparation technology of tea tree oil gel, and evaluate its anti-inflammatory efficacy, antibacterial effect and the irritation. Methods The tea tree oil gel was prepared using the carbomer-940 as gel matrix, Cremophor RH-40 and 1,2-propylene glycol as solvents. The appearance characters, pH value, viscosity, moisture retention, drug content, and the stability were observed. The anti-inflammatory efficacy, the antibacterial effect and the irritation of tea tree oil gel were evaluated. Results The prescription of tea tree oil gel was selected as following tea tree oil (1.0%), Cremophor RH-40 (5.0%), 1,2-propylene glycol (5.0%), Carbomer-940 (0.6%), glycerol (8.0%), with distilled water 100 g, adjusting pH to 5.0 by triethanolamine. The gel exhibited transparent, well uniformity, appropriate viscosity and fine coating expansion performance, with pH value of 5.52 ± 0.03, viscosity at (48 782 ± 25) mPa•s, the moisture retaining rate of (93.32 ± 0.38)% for 24 h test, containing tea tree oil of (9.55 ± 0.10) mg/g. The inhibition rate of tea tree oil gel on the mouse auricle swelling was 46.15%, which was significantly different as compared to the negative control group (P < 0.01). The diameters of inhibition zone of the gel against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa respectively was (15.50 ± 0.96), (15.25 ± 2.36), and (15.75 ± 1.91) mm. The half hemolysis rate (LC50) and the hemoglobin degeneration index (DI) respectively were 456 157 mg/L and 157.98%. The tea tree oil gel had no eye irritation in rabbits based on the value of LC50/DI 2 887.44. Fourteen consecutive’days administration indicated that the tea tree oil gel had no skin irritation in rabbits. The illumination score of irritative reaction to the rabbit skin was 0.125 after a single administration, while that was 0.036 after successive administration experiment. The results of high speed centrifugalization cold- resistance and heat-resistance tests showed that the preparation exhibited good stability, which needed to be kept tightly in a cool place and protected from light. Conclusion The formulation design was reasonable, while the preparation technology was simple, corresponding to the main index of the gel for topical application, with good anti-inflammatory efficacy, antibacterial effect and safety, which offered the basis for further research and development of tea tree oil.

Objective: To study the prescription and preparation technology of tea tree oil (TTO) microemulsion gel. The quality and the stability were evaluated. Methods: The prescription and preparation technology were selected and optimized through the compatibility test and the pseudo-ternary phase diagram. TTO microemulsion gel was prepared by adding gelatin. The appearance, pH value, viscosity, moisture rate, and the drug concentration were evaluated. Results: The prescription composition of TTO microemulsion gel was TTO (0.6%), Cremophor RH-40 (1.2%), PEG 400 (0.2%), carbopol-980 (0.2%), glycerol (2%), with distilled water adding to 50 g. The optimum formulation exhibited clear and transparent, uniform exquisite, moderate viscosity, and well spreadable, with the particle diameter of (38.38 ± 2.30) nm, zeta potential of (-56.00 ± 5.82) mV, pH value of 5.52 ± 0.01, viscosity of (48 834 ± 5) Pa·s, moisture rate of (96.74 ± 0.52)%, and the drug-loaded of (5.79 ± 0.03) mg/g. The result of heat and cold resistance test showed that the preparation was needed to be stored at low-temperature. Conclusion: The preparation of TTO microemulsion gel is simple, corresponding to the main index of gelata for topical drug delivery preparation and offering the basis for further research and development.

Objective: To study the prescription and preparation technology of tanshinone IIA for oral self-microemulsifying drug delivery system. The quality, stability, and in vitro dissolution were evaluated. Methods: The prescription and preparation technology were selected and optimized through the solubility experiment, orthogonal design, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter, and stability as selection indexes. The droplet morphous, particle size, drug content, stability, and in vitro dissolution were evaluated after self-microemulsification. Results: The prescription composition of tanshinone IIA self microemulsion was aethylis oleas (50%), polysorbate 80 (40%), and PEG 400 (10%), with oil phase-aqueous phase of 1:50, drug-loaded of 3.0 mg/g, and self-emulsifying time of 1 min. The acquired tanshinone IIA self-microemulsion exhibitted uniform and transparent, with the particle diameter of (51.39 ± 1.50) nm, polydispersity index of 0.211 ± 0.022, Zeta potential of (-11.35 ± 1.19) mV. The results of in vitro dissolution indicated that the accumulative dissolution in 0.1 mol/L HCl solution was able to reach 96% after 30 min. The stability result showed that tanshinone IIA self-microemulsion was affected by high temperature and illumination, indicating having to be stored at 4℃ and protected from light. Conclusion: The preparation of tanshinone IIA self-microemulsion is simple, increasing the solubility in water, making it better absorption in the stomach and intestine, corresponding to the main index of oral drug delivery system and offering the basis for further development and research about tanshinone IIA.

Objective To compare the difference in clinical prognosis of patients with low malignant obstructive jaundice treated by percutaneous biliary stent insertion across or above the duodenal papilla.Methods 56 patients with malignant biliary obstruction were reviewed retrospectively.Stents were placed above the duodenal papilla in 31 cases (group A) and across the duodenal papilla in 25 cases (group B).Total bilirubin reduction rate after 4-7 days of the procedure, biliary infection rate and stent occlusion rate were evaluated and compared between two groups.Results Mean survival periods were 180.3±142.5 days for group A and 178.6±137.7 days for group B (P=0.840).Total bilirubin level was decreased by 42.0±43.6% for group A and by 41.4±28.7% for group B after 4-7 days of the procedure(P=0.950);clinical success rates were 93.5% for group A and 92.0% for group B (P=1.0).Post-procedure cholangitis occurred in 7 cases (22.6%) in group A and 5 cases (20.0%) in group B (P=0.815).Stent occlusion rates were 22.6% and 28.0% for group A and group B (P=0.642).Conclusion For patients with lower malignant biliary obstruction, both of the two modalities of stent placement are safe and effective treatment.Stent placement across the duodenal papilla do not increase the development of stent occlusion or cholangitis compared with stent placement above the duodenal papilla.

AIM: To observe the changes of macular retinal structure and microcirculation in patients with pituitary adenoma(PA)by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 40 PA patients treated at the department of neurosurgery, Affiliated Hospital of Guangdong Medical University from September 2021 to March 2023 were included as PA group, and 42 age- and gender-matched healthy volunteers were selected as normal control group. All patients underwent visual field, OCT and OCTA examinations, and the correlation of ocular parameters in PA patients was analyzed.RESULTS:The vessel density(VD)of each retinal layer in the macular area of the PA group was lower than that of the normal control group, and the superficial vascular complex(SVC)-VD in the macular area was positively correlated with the thickness of the macular ganglion cell complex(mGCC)(except the nasal side of the inner ring and the lower part of the outer ring; P<0.05). The thickness of mGCC in each quadrant of the macular area and the thickness of the circumpapillary retinal nerve fiber layer(CP-RNFL)in each quadrant were negatively correlated with the mean defect(MD)value of the visual field(P<0.05), and the area of the foveal avascular zone(FAZ)was positively correlated with the MD value(P<0.05).CONCLUSION:The combination of OCT and OCTA can fully understand the microscopic changes of retinal structure and microcirculation function in PA patients, which is of great value in evaluating the preoperative visual function of PA patients.

OBJECTIVE: To screen small molecule metabolites of dibutyl phthalate( DBP) in the rat plasma using ~1H nuclear magnetic resonance( NMR) technology; and to clarify the changes of metabolites and possible mechanism in metabolic regulation of DBP in rats from the molecular level and the aspects of material and energy metabolism. METHODS: According to random number table method,twenty-four specific pathogen free SD male rats were divided into four groups: control group,low dose group,middle dose group and high dose group with the given dose of 0,500,1 000 and1 500 mg / kg of body mass,respectively. After giving DBP of gavage once a day for two weeks,the plasma samples were obtained,and ~1H NMR spectra was recorded. The plasma metabonomic profiles were analyzed using pattern recognition.Difference metabolites were screened by principal components analysis,partial least squares-discriminate analysis and orthogonal partial least squares-discriminate analysis. Biomarkers was screened by variable importance in the projection norm. RESULTS: There were changes of twelve important metabolites in the plasma metabonomic profiles between DBP treatment groups and control group. The differences of metabolites had dose-effect relationship. Plasma levels of high density lipoprotein cholesterol, low density lipoprotein cholesterol, hydrobutyrate, glycoprotein, citric acid, glucose,creatine phosphate,unsaturated fatty acid,tyrosine and phenylalanine were reduced( P < 0. 05),while lactic acid and pyruvic acid were increased( P < 0. 05). CONCLUSION: DBP induces the metabolic disorders including amino acid metabolism,lipid metabolism and energy metabolism.

ObjectiveTo observe and analyze the vitreoretinal interface changes in type 2 diabetic retinopathy （DR） by using ultra-wide field swept-source optical coherence tomography （UWF SS-OCT） / swept-source optical coherence tomography angiography （SS-OCTA）. MethodsThis study enrolled 143 patient with diabetic mellitus. We performed SS-OCT on 258 eyes and OCTA on 69 eyes with proliferative diabetic retinopathy （PDR）， then analyzed the images to assess the relationship between posterior vitreous detachment （PVD） and DR severity， and to measure the growth of retinal neovascularization in PDR eyes with different stages of PVD. ResultsPVD stage was negatively correlated with DR severity （Gamma=-0.294， P< 0.001）， that is， the more extensive the vitreoretinal adhesion， the more severe the DR. The negative correlation between PVD stage and DR severity was more evident in patients with diabetes duration more than 10 years （Gamma=-0.620， P< 0.001）. Retinal neovascularization occurred more commonly in the area of vitreoretinal adhesion. ConclusionsThe degree of vitreoretinal adhesion is closely related to the DR severity. It is very important to use SS-OCT to evaluate the vitreoretinal interface in the management of DR patients.