Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial.

Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5-6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64-30.36) and 11.60 (95% CI: 8.28-13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34-0.64, p < 0.0001). IRC-assessed confirmed objective response rate (ORR) was higher (81.68% vs. 70.68%, p = 0.056) and duration of response was longer (median, 25.79 [95% CI, 16.53-29.47] vs. 11.14 [95% CI, 9.23-16.59] months, p = 0.0003) in the envonalkib group compared with the crizotinib group. In participants with baseline brain target lesions, IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib (78.95% vs. 23.81%). Overall survival (OS) data were immature, and median OS was not reached in either group (HR = 0.84, 95% CI: 0.48-1.47, p = 0.5741). The 12-month OS rates were 90.6% (95% CI, 84.0%-94.5%) and 89.4% (95% CI, 82.8%-93.6%) in the envonalkib and crizotinib groups, respectively. Grade ≥3 treatment-related adverse events were observed in 55.73% and 42.86% of participants in the envonalkib and crizotinib groups, respectively. Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.

The Association between TREM2 Gene and Late-Onset Alzheimer's Disease in Chinese Han Population.

OBJECTIVE: The objective of this study was to evaluate the impact of single nucleotide polymorphisms (SNPs) in triggering receptor expressed on the myeloid cells 2 protein (TREM2) gene and their interaction with environmental factors and haplotypes on late-onset Alzheimer's disease (LOAD). METHODS: DNA was extracted from the whole blood of the participants and genotyped using PCR and followed by restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test was used in the control group. Multivariate logistic regression analysis was used to determine the relationship between the 4 SNPs of the TREM2 gene and the risk of LOAD. Generalized multifactor dimensionality reduction was used to test the best interaction combination between SNPs and environmental factors. RESULTS: Logistic regression analysis showed that the T allele of rs75932628 and the T allele of rs2234253 were independently associated with increased risk of LOAD, and adjusted odds ratios (ORs) were 1.81 (1.271-2.35) and 1.59 (1.15-2.03), respectively. However, there was no significant association with LOAD for rs142232675 and rs143332484. We found a best model significantly associated with LOAD risk that consisted of rs75932628 and smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.012). Stratified analysis indicated that current smokers with rs75932628-CT/TT genotype have the highest LOAD risk compared to never smokers with rs75932628 - CC genotype, OR (95% confidence interval) = 2.73 (1.72-3.79). Haplotypes of rs75932628 and rs2234253 were analyzed using the SHEsis online software. However, no haplotype was found to be significantly associated with the risk of LOAD. CONCLUSIONS: The T allele of rs75932628 and the T allele of rs2234253 and interaction between rs75932628 and smoking were all correlated with increased risk of LOAD.

Textual Research on Wuzhuyutang Recorded in Literatures from the Eastern Han Dynasty to Period of Republic of China / 中国实验方剂学杂志

Wuzhuyutang is widely used in clinical practice nowadays due to its remarkable effect. It is the fifth prescription included in Ancient Classic Prescriptions Catalogue （the first batch）. Based on relevant medical literatures from the Eastern Han dynasty to the period of the Republic of China，combined with the methods of phiology and metrology，this paper systematically studies the origin，composition，evolution of prescription meaning，main indications，dosage of prescriptions，processing of various herbs，preparation method and administration method. According to the findings， Wuzhuyutang was created by ZHANG Zhongjing's Treatise on Febrile Diseases in the eastern Han dynasty. It was composed of Euodiae Fructus，Zingiberis Rhizoma Recens，Ginseng Radix et Rhizoma and Jujubae Fructus. In history，it had such synonyms as Zhuyutang，Yicujicuxinfang，Zhuyu Renshentang，Wuyutang，Sanwei Shenyutang，Shenyutang，Sishentang. It can be applied in internal medicine， gynecology，pediatrics，department of facial features and other miscellaneous diseases， which belong to Jueyin liver meridian and is manifested by upwardly reversed turbid Yin and invading other meridians， with cold vomiting （retching or salivation），abdominal pain，headache，dizziness，hand and foot cold as the main clinical symptoms. In terms of dosage，the commonly used dosage of Euodiae Fructus is 3.7-18.6 g in the previous dynasties. In clinical practice，if the main clinical manifestations are vomiting and salivation clearing，the dosage of about 3 g is recommended. Severe headache and abdominal pain can be mainly used，the dosage of about 10 g is recommended. The research and development of the formula can comply with the maximum dose of 5 g as stipulated in the 2015 edition of the Chinese Pharmacopoeia. The dosages of Ginseng Radix et Rhizoma and Zingiberis Rhizoma Recens can be calculated based on 1 liang equivalent to 3 g，and 1-5 pieces of Jujubae Fructus can be added. Zingiberis Rhizoma Recens and Ginseng Radix et Rhizoma should be processed according to the method of the Chinese Pharmacopoeia，reed should be removed，Zingiberis Rhizoma Recens should be washed，then peeled and sliced， and Jujubae Fructus should be dried in the sun，then cut and seeded before being used as medicine.

Main Functions of Traditional Chinese Medicine Classical Prescription Wandaitang / 中国实验方剂学杂志

Wandaitang, which is one of classical traditional Chinese medicine(TCM) prescriptions, is derived from Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology. It is commonly used in modern clinical practice, and included in the Catalogue of Ancient Classical Prescriptions (The First Batch). Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology and Chen Shi-duo' s Bianzhenglu have a complicated relationship. Both of them have another biography, named Nvke Xianfang and Bianzheng Qiwen. The composition of Wandaitang in the four books is slightly different, while the prescription's explanations and other records are almost the same. The research and development of Wandaitang should be based on the records of Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology. Compared with other classical literatures, Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology was published in a late period and less reproduced in other ancient books. To study the function of Wandaitang, we need to analyze the records in the original book. In addition, we need to make a multi-angle analysis by reference to the theory of TCM, the composition of drugs, the significance of compatibility, as well as the understanding of modern famous doctors, clinical reports and experimental studies in all aspects. The study found that the functions of Wandaitang were relatively concentrated, but with wide major functions involving internal medicine, surgery, gynecological, pediatric, andrological and other departments. According to the study, the authors believe that the functions of the classical TCM prescription of Wandaitang are invigorating spleen to eliminate dampness, dispersing the liver and rectifying Qi, and invigorating Yang. It can be used to treat leucorrhea, diarrhea, edema and stranguria with the syndromes of pale, languid, little food, loose stool and depression. Wandaitang can also be used to treat vaginitis, cervicitis, pelvic inflammatory disease, irritable bowel syndrome, chronic colitis, chronic nephritis, nephrotic syndrome and chronic prostatitis.

Textual Research and Suggestions on Dosage of Pinelliae Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

Pinelliae Rhizoma is a toxic traditional Chinese medicine, and its dose differs greatly between at ancient and modern times, so that it is difficult for researchers to determine its dosage during research and development of famous classical formulas. According to the literature research, it is found that the dose of Pinelliae Rhizoma in famous classical formulas has undergone a process from large to small. Based on the principle of " following the classic and conforming to pharmacopoeia" , and in combination with the modern actual situation, the reasonable dose of Pinelliae Rhizoma in the 17 formulas from the Catalogue of Ancient Famous Classical Formulas (The First Batch) is determined. According to the records of the original book, the evolution of past dynasties and the consideration of the current clinical application, dosage regimen and administration methods of the 17 famous classical formulas and so on, the authors suggested that the dosages of Pinelliae Rhizoma in Banxia Houpotang and Maimendong Tang are 15.0 g, its dosages in Wendantang and Sangbaipi Tang are 6.0 g, dosages of Pinelliae Rhizoma in Xuanfu Daizhe Tang, Zhuye Shigaotang, Banxia Xiexintang, Gancao Xiexintang, Huangliantang, Gualou Xiebai Banxiatang, Houpo Mahuangtang and Jinshui Liujunjian are 7.5 g, the dosages of Pinelliae Rhizoma in Zhurutang, Shengyang Yiweitang and Yangweitang are 6.7, 4.5, 5.0 g, respectively, dosages of Pinelliae Rhizoma in Banxia Baizhu Tianma Tang and Huopo Xialing Tang are 5.6 g.

Textual Research of Origin and Clinical Application of Banxia Baizhu Tianma Tang / 中国实验方剂学杂志

After a comprehensive analysis and research of ancient books and literatures， we discovered that six Banxia Baizhu Tianma Tang prescriptions have the same name. It was originally created by LI Gao. The idea of composition has a certain inheritance relationship with ZHANG Yuan-su′s Tianma Banxia Tang and Huatan Yuhu Wan， which are recorded in Prescription of Peaceful Benevolent Dispensary. In later generations， four doctors developed five prescriptions of the same name. CHENG Guo-peng of the Qing dynasty reformed the prescription based on the theory of phlegm and dampness. He reduced tonic components based on LI's ideas to strengthen the expectorant function， and then transformed the prescription into two of the same name， one for headache and the other for vertigo. The latter was recorded in the textbook of Chinese Herbal Medicine and The Catalogue of Classic Prescriptions （batch 1）， which has the greatest impact on the contemporary prescriptions. Its composition is Pinelliae Rhizoma Praeparatum Cum Zingbere et Alumine （5.595 g）， Atractylodis Macrocephalae Rhizoma （11.19 g）， Gastrodiae Rhizoma， Poria， Citri Exocarpium Rubrum （each 3.73 g）， Glycyrrhizae Radix et Rhizoma （2 g）， 2 pieces of fresh Zingberis Rhizoma Recens （about 2 g） and 2 Jujubae Fructus. The botanical origin of these herbs is clear， and the dosage of herbs is safe in accordance with the Pharmacopoeia of the People's Republic of China.P. The total amount of each dose is about 37.975 g， while the daily dosage is not far different from that of invention. Since its invention， it has been mainly used in the treatment of phlegm headache and vertigo caused by wind phlegm disturbance. In modern clinical practice， it is widely used in treating various diseases with vertigo and headache as the main symptoms， mainly including hypertension， acute ischemic stroke， vertebrobasilar insufficiency， cervical spondylosis， primary headache， Meniere's disease and benign paroxysmal positional vertigo. When the syndrome differentiation is consistent with relevant syndrome type with phlegm as the main pathological factor in traditional Chinese medicine， we can modify the prescription as appropriate.

Validation of Dose Conversion of Banxia Houpotang Based on Systematic Evaluation / 中国实验方剂学杂志

There are many different opinions on dose conversion of famous classical formulas from Treatise on Febrile Diseases or Synopsis of the Golden Chamber, which has become a difficult point in research and development of famous classical formulas. At present, the clinical application dose of Banxia Houpotang is similar to the viewpoint that 1 Liang is equivalent to 3 g, in order to provide scientific basis for this conversion method, this paper systematically evaluated the effectiveness of Banxia Houpotang in intervening globus hystericus. Randomized controlled trials (RCTs) of Banxia Houpotang in intervening globus hystericus from CNKI, VIP, Wanfang Data, China Biology Medicine (CBM), Web of Science and PubMed databases were collected online, the retrieval time was from inception to April 1, 2019. Two reviewers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Then, Meta analysis was performed by RevMan 5.3 software. A total of 17 RCTs involving 1 575 patients were included. The effective rate [relative risk (RR)=1.24, 95%confidence interval (CI) (1.18, 1.30), P<0.000 01] and the curative rate [RR=1.76, 95%CI (1.45, 2.15), P<0.000 01] of Banxia Houpotang in intervening globus hystericus were all better than the control group. Current evidence shows that Banxia Houpotang under the conversion of 3 g in 1 Liang has a significant effect on intervention of globus hystericus. Due to the limitations of quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies, but the author suggests that such dose conversion should be considered in the research and development of famous classical formulas.

Analysis of Banxia Houpo Tang Based on Ancient Literatures / 中国实验方剂学杂志

Banxia Houpo Tang is widely used in modern clinics with definite curative effect. It is one of the classic famous prescriptions in the Catalogue of Ancient Classic Famous Recipes（First Batch） published by the State Administration of Traditional Chinese Medicine（TCM） in 2018. Using bibliometrics methods，collect relevant literatures of Banxia Houpo Tang in ancient medical books，analyze and verify the origin，historical evolution，composition，prescription，function，dosage，artillery，preparation method and decoction method of prescription. A total of 259 related ancient literature data were obtained，involving 107 TCM books. The inductive analysis found that Banxia Houpo Tang originated from ZHANG Zhong-jing's Synopsis of the Golden Chamberin the Han dynasty and consisted of the five flavors of Pinelliae Rhizoma，Magnoliae Officinalis Cortex，Poria，Perillae Folium and Zingiberis Rhizoma Recens. Houpo Tang，Qiqi Tang，Siqi Tang，Daqiqi Tang and other synonyms have appeared in the records of medical records of all dynasties. The prescription composition，preparation method and decoction method are used by later generations of medical practitioners. The analysis of related prescriptions is also rarely disputed. The dosage of drugs used in Banxia Houpo Tang can be calculated as 1g or 3 g. The drug processing method is different from the original one. Pinelliae Rhizoma should choose Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine and Magnoliae Officinalis Cortex as "Jianghoupu". The rest of the drug processing methods respect the 2015 edition of Chinese Pharmacopoeia. The cardiology of its treatment has also been extended and expanded. In addition to the symptoms of "burning in the pharynx" recorded by the original party，this side can also be used for heart diseases such as heartache，chest tightness，sorrow，vomiting，choking noisy and other spleen and stomach disease syndrome and spermatorrhea，turbidity，scorching and other lower coke disease syndrome.

Discussion on Use of Pinelliae Rhizoma Processed Products in Famous Classical Formulas / 中国实验方剂学杂志

There are 17 formulas containing Pinelliae Rhizoma in the Catalogue of Ancient Famous Classical Formulas (the First Batch), most of which are only labeled with " washing with decoction" or without any processing method, which is inconsistent with the current use requirements and brings confusion to research and development of related famous classical formulas. Through combing the records of famous classical formulas in the original book, contemporary works and later works, the usage of processed products of Pinelliae Rhizoma in the evolution of past dynasties was contrasted, and the efficacy, indications and compatibility significance of different formulas were analyzed, according to the principle of " respecting the ancient but not confining the ancient" , the authors suggested that the 17 famous classical formulas should use the processed products of Pinelliae Rhizoma in the 2015 edition of Chinese Pharmacopoeia, including Pinelliae Rhizoma Praeparatum, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine and Pinelliae Rhizoma Praeparatum cum Alumine. Among them, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine should be used in Banxia Xiexintang, Gancao Xiexintang, Huangliantang, Xuanfu Daizhe Tang, Zhuye Shigaotang, Banxia Houpotang, Maimendong Tang, Gualou Xiebai Banxiatang, Wendantang, Zhurutang, Jinshui Liujun Jian and Yangweitang, Pinelliae Rhizoma Praeparatum should be used in Shengyang Yiweitang, Houpo Mahuangtang, Banxia Baizhu Tianma Tang and Huopo Xialing Tang, and Pinelliae Rhizoma Praeparatum cum Alumine should be used in Sangbaipi Tang.

[Physiology and genetics research progress of teat traits in pigs].

The pig teat traits are important indices of genetic improvement in pig breeding, which belong to reproductive traits and can directly affect the sows lactation rate and piglet survival rate. Understanding the genetic mechanism underlying the variation of teat traits is of immense value for the improvement of pig reproductive performance. However, the genetic mechanism underlying teat traits (including teat number, type, location distribution, and fluctuating asymmetry) remains elusive. In this review, we summarize the studies on physiology and genetics of teat traits in pigs, including the development process of the mammary gland, the QTL mapping, and candidate gene researches. This review aims to provide a new perspective for the identification of causal mutations and major genes affecting the teat traits and revealing the complex genetic mechanism of the differences in teat number, type and location distribution during embryonic development in pigs.

Raman intensity enhancement of molecules adsorbed onto HfS2 flakes up to 200 layers.

Newly emerging two-dimensional transition metal dichalcogenide HfS2 has received considerable attention recently due to its ultrahigh photoresponsivity, well-balanced carrier mobility and an appropriate band gap which offer potential in electronic and optoelectronic devices. In this work, HfS2 flakes up to 200 layers with varying color contrasts are fabricated and transferred on a SiO2/Si substrate. The Raman intensities of HfS2 flakes and Raman intensities of molecules adsorbed on HfS2 flakes are quantitatively studied both theoretically and experimentally by considering an optical interference effect. The effects of the main experimental factors: thickness of SiO2 and excitation wavelength on Raman intensities are also theoretically investigated. Due to the low absorption of HfS2, many strong high-order interference-induced enhancement peaks are observed which are different from high absorption materials like graphene and MoS2, in which only 2-4 interference-induced enhancement peaks exist. Due to the environmental instability of single layer HfS2 under ambient conditions, multi-layer HfS2 is a better choice than single layer HfS2 as a Raman scattering substrate which has a stronger Raman enhancement and a better environmental stability. The discovery here will expand the application of HfS2 flakes in molecular detection.

Flavonoids from artificially induced dragon's blood of Dracaena cambodiana.

Dragon's blood is a rare traditional medicine used in many countries. Because of its various therapeutic uses, its requirement is increasing dramatically, while formation of dragon's blood need at least several years, so many researchers tried to induce the formation of dragon's blood artificially, but the chemical constituents of artificially induced dragon's blood were rarely studied. In our research, twenty constituents, including three new ones, were isolated from artificially induced dragon's blood of Dracaena cambodiana, five of which are the same with those from natural dragon's blood. In addition, six compounds exhibited cytotoxic activities, and eleven compounds demonstrated antibacterial activities. Artificially induced dragon's blood is expected to be the substituent of natural dragon's blood.

Von Willebrand factor and coagulation factor VIII in Moyamoya disease associated with Graves' disease: A case report.

The present study reported the case of a Chinese boy who was diagnosed with Moyamoya disease (MMD) associated with Graves' disease (GD). An overactivation of von Willebrand factor (vWF) and coagulation factor VIII (FVIII) was identified in the plasma of the patient. Thiamazole and metoprolol treatment was thus administrated. After 2 months of treatment, the patient's thyroid function returned to normal and the neurological symptoms improved gradually. At the same time, the activities of vWF and FVIII were depressed. During the 20-month follow-up, information regarding the neurological symptoms, cerebrovascular imaging, thyroid function, thyroid autoantibodies and coagulation parameters was collected. High levels of thyroid autoantibodies persisted throughout the follow-up period, while other coagulation parameters remained in the normal range. In conclusion, considering the vital role of vWF and FVIII in vascular diseases, it is hypothesized that these two factors may serve an important role in the occurrence of GD associated with MMD.

Label-free LC-MS/MS shotgun proteomics to investigate the anti-inflammatory effect of rCC16.

Clara cell protein (CC16) is an anti-inflammatory protein, which is expressed in the airway epithelium. It is involved in the development of airway inflammatory diseases, including chronic obstructive pulmonary disease and asthma. However, the exact molecular mechanism underlying its anti­inflammatory action remains to be fully elucidated. The aim of the present study was to define the protein profiles of the anti­inflammatory effect of CC16 in lipopolysaccharide (LPS)­treated rat tracheal epithelial (RTE) cells using shotgun proteomics. Protein extracts were obtained from control RTE cells, RTE cells treated with LPS and RTE cells treated with LPS and recombinant CC16 (rCC16). Subsequent label­free quantification and bioinformatics analyses identified 12 proteins that were differentially expressed in the three treatment groups as a cluster of five distinct groups according to their molecular functions. Five of the twelve proteins were revealed to be associated with the cytoskeleton: Matrix metalloproteinase­9, myosin heavy chain 10, actin­related protein­3 homolog, elongation factor 1­α­1 (EF­1­α­1), and acidic ribosomal phosphoprotein P0. Five of the twelve proteins were associated with cellular proliferation: DNA­dependent protein kinase catalytic subunit, EF­1­α­1, tyrosine 3­monooxygenase, caspase recruitment domain (CARD) protein 12 and adenosylhomocysteinase (SAHH) 3. Three proteins were associated with gene regulation: EF­1­α­1, SAHH 3 and acidic ribosomal phosphoprotein P0. Three proteins were associated with inflammation: Tyrosine 3­monooxygenase, CARD protein 12 and statin­related protein. ATPase (H+­transporting, V1 subunit A, isoform 1) was revealed to be associated with energy metabolism, and uridine diphosphate glycosyltransferase 1 family polypeptide A8 with drug metabolism and detoxification. The identified proteins were further validated using reverse transcription­quantitative polymerase chain reaction. These protein profiles, and their interacting protein network, may facilitate the elucidation of the molecular mechanisms underlying the anti­inflammatory effects of CC16.

Long-term expression of zinc transporters in hippocampus following penicillin-induced developmental seizures and its regulation by E-64d.

Autophagy has been shown to be involved in the pathophysiology of developmental seizure-induced brain damage. The present study aimed to examine whether E-64d, an autophagy inhibitor, was able to facilitate developmental seizure-induced hippocampal mossy fiber sprouting, in particular sprouting-associated zinc transporter signals. Recurrent seizures were induced by penicillin every other day in Sprague-Dawley rats from postnatal day 21 (P21). Rats were randomly assigned into the control group (CONT), recurrent seizure group (RS) and the seizure plus E-64d group (E64D). The expression levels of beclin-1 and B-cell lymphoma 2 were analyzed at 1.5, 3, 6 and 24 h after the last seizures using western blot analysis. At P51, mossy fiber sprouting and the mRNA expression levels of zinc transporter 2 (ZnT-2), ZnT-4, ZnT-5, ZnT-6, ZnT-7, divalent cation transporter 1, Zrt-Irt-like protein 6 (ZIP-6), ZIP-7, cathepsin D and cathepsin L in the rat hippocampus were assessed using Timm staining and reverse transcription-quantitative polymerase chain reaction analysis, respectively. Reduced hippocampal mossy fiber sprouting were detected in the E-64d-treated rats compared with the non-treated control. In parallel with these observations, there was a marked reduction in the mRNA expression levels of ZnT-4 at P51 in the E-64d-treated rat hippocampus compared with the non-treated seizure group. Linear correlation analysis showed significant inter-relationship among ZIP-7, ZnT-4, ZnT-5, ZnT-7, cathepsin D and cathepsin L. These results indicate that the ZnT-4/ZIP-7/cathepsin signaling pathway serves a crucial function in the neuroprotective effects of E-64d. Thus, E-64d may offer a novel strategy for the development of therapeutic interventions for developmental seizure-induced brain damage.

[Research advances in diagnosis and therapy of Niemann-Pick disease type C].

Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.

Effect of p27 gene combined with Pientzehuang ([characters: see text]) on tumor growth in osteosarcoma-bearing nude mice.

OBJECTIVE: To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice. METHODS: Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot. RESULTS: The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05). CONCLUSION: p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.

A new flavonone from seeds of Alpinia katsumadai and its neuroprotective effect on PC12 cells.

A new flavonone, named as (2R, 3S)-pinobanksin-3-cinnamate(1), together with six known compounds, pinocem-brin (2), pinobanksin (3), 3-O-acetylpinobanksin (4), galangin (5), kumatakenin(6), and 3-methylkaempferol (7), were isolated from a 95% ethanol extract of seeds of Alpinia katsumadai through a combination of various chromatographic techniques, including silica gel and Sephadex LH-20. The structure of compound 1 was elucidated by spectroscopic data analysis. Compound 1 exhibits a potent neuroprotective effect against the corticosterone-damaged PC12 cells, which may be underlying the effect by scavenging intracellular ROS.

Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus.

E-64d (a calpain and autophagy inhibitor) has previously been shown safe for the treatment of Alzheimer's disease in humans. In the present study, the potential protective mechanism of E-64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin-induced recurrent epilepticus. A seizure was induced by penicillin every other day in Sprague-Dawley rats from postnatal day 21 (P21). The rats were randomly assigned into the control group (CONT1), the control plus E-64d (CONT2), the seizure group (EXP1) and the seizure plus E-64d (EXP2). On P51, mossy fiber sprouting and related gene expression in hippocampus were assessed by Timm staining and real-time RT-PCR methods, respectively. To validate the RT-PCR results, western blot analysis was performed on selected genes. E-64d obviously suppressed the aberrant mossy fiber sprouting in the supragranular region of dentate gyrus and CA3 subfield of hippocampus. Among the total twelve genes, six genes were strongly up- (MT-3, ACAT1, clusterin and ApoE) or down- (ZnT-1 and PRG-3) regulated by developmental seizures (EXP1) compared with that in the CONT1. Up-regulation of ApoE and Clusterin was blocked by pretreatment with E-64d both in mRNA and protein levels. Further, E-64d-pretreated seizure rats (EXP2) showed a significant downregulation of mRNA expression of PRG-1, PRG-3 and PRG-5, cathepsin B and ApoE, as well as up-regulated nSMase and ANX7 in hippocampus when compared with EXP1 rats. The results of the present study suggest that E-64d, an elective inhibitor of calpain and autophagy, is potentially useful in the treatment of developmental seizure-induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE/clusterin pathway in hippocampus.