Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

AIM To improve the quality control method of Zanthoxylum nitidum(Roxb.)DC.METHODS In the TLC qualitative identification of nitidine chloride,chelerythrine and toddalolactone,the analysis was performed on silica gel GF254 TLC plate,chloroform-methanol-ammonia(30∶1∶0.1)was taken as a developing agent.The HPLC fingerprints for Z.nitidum and its adulterants were established.In the HPLC content determination of magnoflorine,nitidine chloride and chelythrine,the analysis was performed on a 30℃ thermostatic Diamonsil Plus column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%trifluoroacetic acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 273 nm.RESULTS The clear TLC plots demonstrated good separation.The similarities of fingerprints for eighteen batches of medicinal materials were 0.484-0.983,Z.nitidum and its adulterants were effectively distinguished.Three constituents showed good linear relationships within their own ranges(R2=1.000 0),whose average recoveries were 98.9%-103.3%with the RSDs of 1.17%-1.96%.CONCLUSION This simple and reproducible can provide a new method for the quality control of Z.nitidum.

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

This study steps through four key principles, four open problems and future perspectives of Chinese materia medica(CMM) ecological agriculture by presenting the historical development, existing theories and practice outcomes. Then, it focuses on refining the main principles of CMM ecological agriculture:(1)the principles of ecological niche associated with yield and comprehensive income;(2)principles of biological diversity associated with the integrated control of diseases, pests and weeds;(3)principles of adversity effects associated with the quality improvement of CMM;(4)principles of structural stability associated with the sustainable development of CMM ecological agriculture. On this basis, four burning issues of CMM ecological agriculture were obtained,(1)ecological planting mode and supporting technologies need to be perfect;(2)multi-integrated industrial coupling remains to strengthen;(3) quality assurance system of CMM ecological agriculture and high-quality and favorable price model remains to be formed;(4)awareness of the demonstration and extension of CMM ecological agriculture needs to be desired. Finally, suggestions for the sustainable development of CMM ecological agriculture are put forward:(1)strengthen the national planning and layout, develop CMM ecological agriculture accor-ding to local conditions;(2)pay equal attention to inheritance and innovation, and strengthen the theory and practical technology research of CMM ecological agriculture;(3)strengthen industrial coupling and realize the transformation of CMM ecological agriculture from a production-based to a multi-in-one compound model;(4)intensify standards and brands, building a quality assurance system for CMM ecological products;(5) publicize the demonstration and popularization of CMM ecological agriculture. In summary, the development of CMM ecological agriculture possessed a firmer theory and practice foundation, although there is still much room for improvement. A better field of Chinese medicine agricultural development with immense economic and social benefits will not a question of "if" but "when" by accurately grasp the way forward.
Agriculture ; China ; Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional

This paper analyzed life form, habitats and environmental stresses of medicinal plants and algal fungi collected in Chinese Pharmacopoeia(2015). ①It was found that only 0.94% of the medicinal plants mainly cultivated in field. The most common habitats of medicinal plants are divided into two types: those whose natural habitats are forest margins/undergrowth(about 42.53%) and those whose natural habitats are roadside, hillside, wasteland/sand(about 43.78%). The former mainly faces environmental stresses such as weak light, pests and diseases; the latter often faces the main environmental stresses of drought, strong light, ultraviolet radiation, high temperature, low temperature(day and night or annual temperature difference is large), nutrient deficiency, pests and so on. ②Based on analyzing the strategies of medicinal plants to adapt to environmental stresses, it is pointed out that the synthesis and accumulation of secondary metabolites are the most important strategies of medicinal plants to protect against environmental stresses. In the process of long-term adaptation to specific stress, the accumulation of relevant genetic variation and epigenetic inheritance has become an important condition for the formation of quality of medicinal plants. ③It is proposed that "simulative habitat cultivation" has obvious advantages in balancing growth and secondary metabolism and guaranting the quality of traditional Chinese medicinal materials.
Drugs, Chinese Herbal ; Ecosystem ; Medicine, Chinese Traditional ; Plants, Medicinal ; Ultraviolet Rays

Objective?To evaluate the application of two kinds of retroperitoneal laparoscopic nephroureterectomy in upper urinary tract urothelial carcinoma and select the best operative approaches.?Methods?The clinical data of 40 cases of retroperitoneal laparoscopic surgery in patients with upper urinary tract tumor were analyzed. Among the 40 patients, 21 cases (14 males and 7 females) underwent modified retroperitoneal laparoscopic nephroureterectomy combined with transurethral incision of the ureteral orifice (group A), and 19 cases (13 males and 6 females) underwent retroperitoneal laparoscopic nephroureterectomy combined with hypogastrium minor incision and transurethral incision of the ureteral orifice (group B). The operative time, the blood loss, the retention time of drainage tube, the first exhaust time of postoperative and the hospital stay were compared between the two groups.?Results?The operation was successfully completed in all the 40 cases without conversion to open surgery. The operative time in group A was significantly shorter than that in group B (P < 0.01), and the hospital stay was significantly shorter than that in group B (P < 0.05). There were no statistical differences in blood loss, the retention time of drainage tube, and the first exhaust time of postoperative between the two groups (P > 0.05).?Conclusions?Compared with the retroperitoneal laparoscopic nephroureterectomy combined with hypogastrium minor incision, the modified retroperitoneal laparoscopic nephroureterectomy is safe and effective, which can shorten the operative time and reduce hospital saty. Tumor located in renal pelvis and the proximal &middle part of ureter, modified retroperitoneal laparoscopic nephroureterectomy combined with transurethral incision of the ureteral orifice is the most effective method.

AIM:To investigate the effect of interference in Yes-associated protein(YAP)expression on blad-der cancer cell apoptosis and its mechanisms.METHODS:Bladder cancer cell line T-24 was used as the target and divid-ed into control group(no treatment),small interfering RNA negative control(siRNA-NC)group,and YAP siRNA group. The expression levels of YAP at mRNA and protein levels in the transfected cells of each group were detected by real -time PCR and Western blot,respectively.The cell viability was measured by MTT assay.The apoptosis was analyzed by flow cytometry.The protein expression levels of β-catenin and c-Myc were determined by Western blot.The cells in YAP siRNA group were treated with Wnt/β-catenin signaling pathway inhibitor FH 535, and then the cell viability and apoptosis were analyzed by MTT assay and flow cytometry,respectively.RESULTS:The expression of YAP at mRNA and protein levels in YAP siRNA group was significantly lower than that in control group(P<0.05).The cell viability and the expression levels of c-Myc and β-catenin in YAP siRNA group were significantly lower than those in control group(P<0.05),while the apoptotic rate was significantly higher than that in control group(P<0.05).The cell viability in YAP siRNA+FH535 group was decreased significantly,while the apoptotic rate was increased as compared with YAP siRNA group(P<0.05). CONCLUSION:Interfering with the expression of YAP inhibits the viability of bladder cancer cells by inhibiting the Wnt /β-catenin signaling pathway,thus promoting apoptosis of bladder cancer cells.

Objective To investigate minimal inhibitory concentration (MIC) of ciprofloxacin against Pseudomonas aeruginosa induced by Pseudomonas quinolone signal (PQS) and ciprofloxacin in vitro.Methods Clinical isolates of Pseudomonas aeruginosa sensitive to ciprofloxacin were collected and then induced ciprofloxacin with three concentrations of 0.5 × MIC,2 × MIC and 4 × MIC,and PQS with three concentrations of 10,40,80 μmol· L-1,respectively for five days.The agar dilution method was used to measure MICs of all strains before and after inductions to ciprofloxacin.The MICs to ciprofloxacin before and after inductions of the same induction scheme were analysed by repeated measures analysis of variance and Paired t-test was used to compare the MICs of two induced schemes.Results Twelve clinical isolates of Pseudomonas aeruginosa sensitive to ciprofloxacin were obtained,among them one was used as the quality control strain included.There had interaction between induction time and induction concentrations of PQS or ciprofloxacin (P ＜0.001 or P ＜0.05).MICs of strains to ciprofloxacin of two induced schemes had statistically significant difference (P ＜ 0.05).Conclusion Under different concentrations of PQS,the trend of MIC values of ciprofloxacin to Pseudomonas aeruginosa varied by induction time.Under different concentrations of ciprofloxacin,MIC values tended to increase with the prolongation of induction time.The effects of two induction schemes on MIC of ciprofloxacin were different.