Research progress in tumor microenvironmentally modulating nanostructures / 药学学报

Tumor microenvironment (TME) is a complex comprehensive system composed of immune cells, inflammatory cells, tumor-associated fibroblasts, microvessels, and various cytokines and chemokines. As the living environment of tumor cells, it's closely related to the occurrence, metastasis, and recurrence of tumors. The characteristics of tumor microenvironment include: weakly acidic environment, low oxygen, high concentration of reactive oxygen species (ROS) and reducing substances, immunosuppression, etc. A weakly acidic environment favors metastasis of tumor cells, hypoxia is conducive to the emergence of drug resistance, high concentration of ROS and reducing substances are beneficial for tumor treatment, and immunosuppressiveness facilitates immune escape. With the rapid development of nanotechnology, more and more nanostructures have been reported to achieve tumor treatment by regulating the tumor microenvironment. This review summarizes recent advances in the nanostructures used to regulate tumor microenvironment through changing elements, including hydrogen-ion concentration (pH), the concentration of oxygen (O2) and reactive oxygen species, and the activity of immune cells. Moreover, research directions in the future are pointed out in this review.

Cordblood-Based High-Throughput Screening for Deafness Gene of 646 Newborns in Jinan Area of China

OBJECTIVES: Infants with slight/mild or late-onset hearing impairment might be missed in universal newborn hearing screening (UNHS). We identified the mutation hot spot of common deaf gene in the newborns in Jinan area population by screening the mutation spot with neonate cord blood, in order to make clear whether the neonate cord blood for screening is feasible. METHODS: Six hundred and forty-six newborns were subjected to both UNHS and genetic screening for deafness by using neonate cord blood. The newborn genetic screening targeted four deafness-associated genes, which were commonly found in the Chinese population including gap junction beta-2 protein (GJB2), gap junction beta-3 protein (GJB3), solute carrier family 26 member 4 (SLC26A4), and mtDNA 12S rRNA. The most common 20 spot mutations in 4 deaf genes were detected by MassARRAY iPLEX platform and mitochondrial 12S rRNA A1555G and C1494T mutations were sequenced using Sanger sequencing. RESULTS: Among the 646 newborns, 635 cases passed the UNHS and the other 11 cases (1.7%) did not. Of the 11 failures, two cases were found to carry homozygous GJB2 p.R143W pathogenic mutation, one case was found to have heterozygous GJB2 235delC mutation, and another one case carried heterozygous GJB3 p.R180X pathogenic mutation. Six hundred and thirty-five babies passed the newborn hearing screening, in which 25 babies were identified to carry pathogenic mutations, including 12 heterozygotes (1.9%) for GJB2 235delC, eight heterozygotes (1.3%) for SLC26A4 IVS7-2A>G, one heterozygote (0.2%) for p.R409H, two homozygotes (0.3%) for m.1494C>T, and two homozygotes (0.3%) for m.1555A>G. CONCLUSION: Newborn genetic screening through the umbilical cord blood for common deafness-associated mutations may identify carriers sensitive to aminoglycoside antibiotic, and can effectively prevent or delay hearing loss occurs.

Formulation optimization of Kyllinga brevifolia total flavonols solid dispersion controlled porosity osmotic pump tablets / 中草药

Objective: To prepare Kyllinga brevifolia total flavonols (KBTF) solid dispersion controlled porosity osmotic pump tablets, and investigate the effects of core tablets and coating on its in vitro drug release behavior, so as to optimize the formulation. Methods: Using KBTF solid dispersion prepared by solvent method as drug core to increase the dissolution of KBTF in vitro, the optimal forrmulation of KBTF solid dispersion controlled porosity osmotic pump tablets was selected via the single factor investigation and orthogonal design. Results: The optimal formula was as follows: osmotic promoter was sodium chloride 100 mg, content of PEG 400 was 150%, content of DBP was 20%, and rate of weight growth of coating membrane was 2%. Conclusion: KBTF solid dispersion controlled porosity osmotic pump tablets with optimal forrmulation can stably release drugs in 12 h and the accumulative drug release rate was more than 90%, whilst its in vitro drug release behavior was up to the character of zero-order drug release.

Paparation of solid dispersion of Kyllinga brevifolia total flavonols and its properties / 中草药

Objective: To prepare the solid dispersion of Kyllinga brevifolia total flavonols (KBTF) for improving the dissolution rate of KBTF. Methods: The solid dispersion was prepared by the melted and dissolved method with the carriers of PVP K30, PEG 6000, PEG 4000, and Poloxamer 188 and the in vitro dissolution of KBTF solid dispersions was performed. The structure of the solid dispersion was characterized by SEM and IR. Results: The solid dispersion prepared with PVPK30 as carrier is better to improve the dissolution than those with other carriers, and drug-carrier (1:2) is the best. The results of SEM and IR showed that KBTF in solid dispersion took amorphous form. Conclusion: The solid dispersion technology can significantly increase the dissolution of KBTF in vitro.

Clinical effects of soluble interleukin-6 receptor detection on autoimmune rheumatic disease patients

This study aims to explore the effects of soluble interleukin-6 receptor [IL-6R] on the clinical diagnosis and treatment of autoimmune rheumatic disease [ARD] patients. Sixty-eight ARD patients enrolled in our hospital recently were selected, the IL-6R levels of whom were detected by double-antibody sandwich ELISA method and compared with the IL-6 levels of normal subjects. The expressions of IL-6R in joint tissues were detected by section staining. The mechanism regarding the effects of IL-6R was postulated by administering the patients with blocking agent. The blood IL-6R level of ARD patients was 2-3 times higher than the IL-6 level of normal subjects with significant difference. The detection results of C-reactive protein and erythrocyte sedimentation rate show that both the indicators were significantly decreased [P=0.0098 and 0.0097 respectively]. IL-6R was associated with autoimmunity based on the considerable expression in tissue sections, which was also verified by the alleviated symptoms after blocking IL-6R expression. Detecting soluble IL-6R is able to determine the patient's conditions and treatment effects. Meanwhile, soluble IL-6R detection can also serve as the inflammatory responses of ARD, as well as the determination index for abnormal immune responses and generated antibodies number, which is crucial for early diagnosis

Effects of valsartan combined with amlodipine or hydrochlorothiazide regimen on blood pressure variation in elderly hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of valsartan combined with amlodipine or hydrochlorothiazide regimen on blood pressure variation and plasma nitric oxide (NO) and endothelin (ET) in elderly hypertensive patients.</p><p><b>METHODS</b>A total of 61 elderly patients with grade 2 or 3 hypertension were randomized into valsartan + amlodipine (the amlodipine group, n = 31) or valsartan + hydrochlorothiazide (the hydrochlorothiazide group, n = 30) group. Blood lipids, fasting plasma glucose and uric acid were determined before the treatment. 24-hour dynamic blood pressure, NO and ET were monitored at baseline, 8 and 16 weeks after treatment.</p><p><b>RESULTS</b>24 hours blood pressure and daytime blood pressure were similar between two groups at all 3 time points. At 16 weeks, morning systolic blood pressure surge was significantly lower in amlodipine group than in hydrochlorothiazide group [(22.6 ± 8.8) mm Hg (1 mm Hg = 0.133 kPa) vs. (26.3 ± 13.7) mm Hg, P < 0.05]. 24 hours systolic blood pressure variability (SBPV) decreased progressively in both groups [the amlodipine group: (12.5 ± 2.8) mm Hg vs. (10.2 ± 2.2) mm Hg vs. (8.8 ± 1.6) mm Hg, P < 0.01; the hydrochlorothiazide group: (12.5 ± 2.5) mm Hg vs. (10.7 ± 2.2) mm Hg vs. (9.6 ± 2.0) mm Hg, P < 0.01]. Daytime SBPV also decreased progressively in both groups [the amlodipine group: (12.2 ± 3.0) mm Hg vs. (10.1 ± 2.3) mm Hg vs. (8.4 ± 1.9) mm Hg, P < 0.01; the hydrochlorothiazide group: (11.8 ± 2.7) mm Hg vs. (10.4 ± 1.9) mm Hg vs. (9.6 ± 2.2) mm Hg, P < 0.01]. 24 hours diastolic blood pressure variability (DBPV) was significantly reduced post therapy in the amlodipine group [(15.5 ± 3.4) mm Hg vs. (13.0 ± 3.5) mm Hg vs. (12.3 ± 2.5), P < 0.01] but not in the hydrochlorothiazide group. NO increased progressively [(27.3 ± 13.6) µmol/L vs. (47.2 ± 16.3) µmol/L vs. (69.5 ± 18.9) µmol/L in the amlodipine group, P < 0.01; (33.5 ± 13.9) µmol/L vs. (49.7 ± 21.9) µmol/L vs. (66.7 ± 24.7) µmol/L in the hydrochlorothiazide group, P < 0.01] and ET decreased progressively [(45.3 ± 8.0) ng/L vs. (37.4 ± 3.9) ng/L vs. (34.2 ± 4.4) ng/L in the amlodipine group, P < 0.01; (46.6 ± 10.4) ng/L vs. (37.0 ± 5.4) ng/L vs. (36.1 ± 8.2) ng/L in the hydrochlorothiazide group, P < 0.01] in both groups.</p><p><b>CONCLUSION</b>Valsartan in combination with amlodipine or hydrochlorothiazide can both effectively lower BPV in elderly hypertensive patients and improve the vascular endothelial function and the former regimen is more suitable for elderly hypertensive patients.</p>

Clinical observation on strong stimulation of acupoints around eyes for treatment of adolescent myopia / 中国针灸

<p><b>OBJECTIVE</b>To observe the therapeutic effect and influential factors of strong stimulation of acupoints around eyes by reducing method of twisting the needle for treatment of adolescent myopia, and to compare the different curative effects of both weak and strong stimulus intensities and wearing glasses in daytime.</p><p><b>METHODS</b>According to the principle of knowing and permission, the patients were divided into a strong stimulation group (60 cases, 120 eyes), a weak stimulation group (60 cases, 120 eyes) and a wearing glasses group (60 cases, 120 eyes). Both the strong stimulation group and the weak stimulation group were treated by reducing method of twisting the needle, with Cuanzhu (BL 2), Yuyao (EX-HN 4), Sizhukong (TE 23), Sibai (ST 2) and Taiyang (EX-HN 5) selected. Each acupoint was twisted 360 and 90 times per min for the strong stimulation group, and 90 degrees and 60 times per min for the weak stimulation group; the wearing glasses group were not treated with acupuncture, but with wearing glasses in daytime.</p><p><b>RESULTS</b>After treatment with the reducing method of twisting the needle, the vision improved (P < 0.01), with more obviously increased in the strong stimulation group than the weak stimulation group (P < 0.01), and there was no significant change of vision in the wearing glasses group. The age and the myopic degree of the patient before treatment were closely related with the change of vision after treatment (P < 0.01).</p><p><b>CONCLUSION</b>The reducing method of twisting the needle has a definite clinical therapeutic effect on adolescent myopia; strong stimulation has a better effect than the weak one; the age and the myopic degree of the patient possibly influence the therapeutic effect.</p>