Analysis of the marketing of rare disease drugs in China based on the First Batch of Rare Disease Catalog / 中国药房

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

Analysis of the marketing of rare disease drugs in China based on the First Batch of Rare Disease Catalog / 中国药房

OBJECTIVE To investigate the marketing status， general characteristics， and time trends of rare disease drugs in China. METHODS Based on 121 kinds of rare diseases included in the First Batch of Rare Disease Catalog， the names and marketing approval information of corresponding drugs with indications were obtained from the databases of the Center for Drug Evaluation， National Medical Products Administration and Yaozhi.com， and the relevant characteristic variables were extracted for descriptive statistical analysis. RESULTS As of December 31， 2022， only 32 of 121 rare diseases have therapeutic drugs available for treatment on the market in China， and 79 rare disease drugs have been approved. Among them， 46.84% of the drugs are domestic drugs， 88.61% of the drugs are approved for use in both adults and children； 67.09% are chemicals and 59.49% are injections. According to the ATC classification， Category A （digestive system drugs） is the most， accounting for 20.25%. The number of rare disease drugs on the market each year is the highest in 2021， with an overall upward trend from 2018 to 2021 and a downward trend in 2022. Among rare disease drugs on the market each year， according to the ATC classification， the number of Category L （antineoplastics and immune inhibitors） will be the largest in 2021， being 5. By dosage form， oral medicines were marketed in the largest number in 2022， and injectable medicines in 2021. CONCLUSIONS In recent years， the number of approved rare disease drugs in China has been continuously increasing， but it is still far from meeting the needs of patients， and there is still a lack of domestically approved rare disease drugs. We should further accelerate the research and development of rare disease drugs， and promote the import and replication of rare disease drugs.

Clinicopathological features and prognostic analysis of primary duodenal adenocarcinoma / 中华普通外科杂志

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Investigation and analysis on the parents ’behavior of children ’s use of antibiotics in Sichuan-Chongqing area / 中国药房

OBJECTIVE To provide reference for the safety of drug use in children and the rational drug use management strategies by health administration departments. METHODS A self-designed questionnaire was used to investigate the cognition of antibiotics and the parents ’behavior of children ’s use of antibiotics ，using online and offline questionnaires. Univariate analysis was carried out on the scores of respondents ’cognition，and multivariate Logistic regression analysis was carried out on the factors affecting parents ’behavior of children ’s use of antibiotics. RESULTS A total of 1 068 questionnaires were distributed ，and 993 valid questionnaires were recovered ，with the effective recovery rate of 93.0％. Among the respondents ，43.2％ of the parents ’ behavior of children ’s use of antibiotics in the past 6 months. The score of respondents ’cognition，high treatment cost and cumbersome treatment procedures ，easy access to antibiotics ，certain medication experience ，the recommendation of pharmacists in drug store ，the recommendation of relatives and friends and the publicity of mass media were positively correlated with parents ’ behavior of children ’s use of antibiotics （P＜0.05）. CONCLUSIONS The rate of the parents ’in Sichuan-Chongqing area is high ， which is the result of a combination of several factors. Reducing the risk of behavior of children ’s use of antibiotics requires the joint efforts of the government ，medical institutions and the public. The parents ’cognition towards antibiotics should be improved ，and the acquisition of antibiotics should be standardized so as to reduce unreasonable use of antibiotics.

Exosomal miR-574-5p Promotes Proliferation, Invasion and Migration of Glioma Cells by Down-regulating LATS2 / 中国生物化学与分子生物学报

Exosomes are involved in invasion, migration and angiogenesis of tumor cells, and invasion is the main cause of death in glioma patients. Studies have shown that the exosomes secreted by tumor cells can carry miRNA into the receptor cells and regulate the biological functions of the receptor cells, such as proliferation, migration and invasion. miR-574-5p plays a key role in the occurrence and development of a variety of tumors. However, whether the exosomes derived from glioma cells express miR-574-5p and its role in the growth, invasion and migration of glioma cells have not been reported. This study investigated the mechanism of the exosomal miR-574-5p secreted from glioma cells in the process of cell proliferation, migration and invasion. The exosomes were characterized by electron microscopy, nanoparticle size tracking and Western blot. The results displayed that the extracted exosomes were round particles with a diameter of 30 ~ 100 nm. The internalization of exosomes was detected by immunofluorescence assay. The results showed that exosomes were internalized into LN229 cells; Bioinformatics and online data were used to screen the differentially secreted miRNA between LN229 and H4 glioma cells. The results showed that the differentially secreted miRNA was miR-574-5p, and large tumor suppressor 2 (LATS2) was predicted to be the target gene of miR-574-5p; Duel luciferase reporter assay confirmed that miR-574-5p was complementary to the 3'UTR region of LATS2; The transfection assay, qRT-PCR and Western blot was conducted to measure the relationship between miR-574-5p and LATS2. The results demonstrated that there was no significant difference in LATS2 mRNA levels between the control group and the group with miR-574-5P overexpression (P > 0.05), suggesting the regulatory effect of miR-574-5P on LATS2 was achieved by inhibiting its translation (P < 0.05). CCK-8, Transwell migration and invasion assays were conducted to explore the effect of miR-574-5p on proliferation, migration and invasion of LN229 cells. The results showed that overexpression of miR-574-5p could significantly promote the ability of proliferation, migration and invasion of LN229 cells (P < 0.05). In addition, Western blot was performed to measure the expression of kinase proteins involved in the LATS2/YAP signaling pathway, and the influence of the exosomes on this signaling pathway. The results revealed that the exosomes down-regulated the protein expression level of LATS2 and reduced p-YAP phosphorylation. In conclusion, the exosomal miR-574-5p can promote the proliferation, migration and invasion of glioma cells by down-regulating LATS2 and activating LATS2/YAP signaling pathway, which may provide a potential biomarker for the diagnosis and target for the treatment of glioma.

DEPTOR improves cisplatin chemosensitivity in esophageal squamous cell carcinoma cells by inducing Caspase-1-mediated pyroptosis / 药学学报

Chemotherapy resistance is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Pyroptosis is one of the anti-tumor mechanisms by chemotherapy drugs. Studies have shown that DEP-domain containing mTOR-interacting protein (DEPTOR) is correlated with sorafenib and gefitnib resistance, which is discovered as a naturally negative regulator of mammalian/mechanistic target of rapamicin (mTOR). In this study, DEPTOR knockdown (shDEPTOR) lentivirus was used to establish the stable DEPTOR knockdown ESCC cell lines. The results showed that knockdown of DEPTOR reduced chemosensitivity to cisplatin in ESCC cells in vitro. The lower expression of DEPTOR caused less extensive morphological characteristics of pyroptosis than that was observed in sh-con cells with the treatment of cisplain. Further studies showed that knockdown of DEPTOR induced downregulation of Caspase-1 expression and reduction of Caspase-1 activation, thereby inhibiting the activation of the classical pathway of pyroptosis. This paper demonstrates that DEPTOR can improve cisplatin chemosensitivity in ESCC cells via inducing Caspase-1-mediated pyroptosis.

Effects of EI injection on Brain Energy and PI3K/AKT Signaling Pathway in IBO Basal Nucleus Microinjected with Dementia Model Rats / 世界科学技术-中医药现代化

Objective: To investigate the effects of EI injection on learning and memory ability and brain energy of two-way Meynert basal injection of Ibotenic acid (IBO) dementia model rats. Methods: A rat model of dementia wasestablished by bilateral meynert basal injection of IBO. After 8 weeks of EI injection, Morris water maze was used todetect the learning and memory ability of rats. Congo red staining was used to observe the deposition of Aβ plaque inhippocampal CA1 and cortical areas of rats. The changes of ATP, ADP and AMP in brain tissue of each group weredetermined by HPLC. The content of insulin in rat brain tissue was detected by ELISA kit. The expression of key proteinin PI3K/AKT signaling pathway was detected by Western blot. Results: Compared with the sham operation group, theescape latency of the model group was significantly prolonged, the number of entering the platform, the time andpercentage of crossing the platform quadrant decreased significantly (P ＜ 0.05); Aβ plaque deposition was observed inthe hippocampus and cortex; ATP/AMP ratio and insulin content were significantly decreased (P ＜ 0.05); brain tissue PI3 K and AKT protein were low expression (P＞ 0.05) . After intervention with EI injection, the escape latency of themodel rats was significantly shortened, the number of entering the platform and the time of crossing the platform quadrantincreased significantly (P ＜ 0.05); the hippocampus and cortex red staining was alleviated; the brain tissue ATP/AMPratio and insulin content increased significantly (P ＜ 0.05) . Conclusion: EI injection can improve the learning andmemory function of IBO-induced dementia model rats, which is related to the improvement of brain energy.

Chicken RNA-binding protein T-cell internal antigen-1 contributes to stress granule formation in chicken cells and tissues

T-cell internal antigen-1 (TIA-1) has roles in regulating alternative pre-mRNA splicing, mRNA translation, and stress granule (SG) formation in human cells. As an evolutionarily conserved response to environmental stress, SGs have been reported in various species. However, SG formation in chicken cells and the role of chicken TIA-1 (cTIA-1) in SG assembly has not been elucidated. In the present study, we cloned cTIA-1 and showed that it facilitates the assembly of canonical SGs in both human and chicken cells. Overexpression of the chicken prion-related domain (cPRD) of cTIA-1 that bore an N-terminal green fluorescent protein (GFP) tag (pntGFP-cPRD) or Flag tag (pFlag-cPRD) induced the production of typical SGs. However, C-terminal GFP-tagged cPRD induced notably large cytoplasmic granules that were devoid of endogenous G3BP1 and remained stable when exposed to cycloheximide, indicating that these were not typical SGs, and that the pntGFP tag influences cPRD localization. Finally, endogenous cTIA-1 was recruited to SGs in chicken cells and tissues under environmental stress. Taken together, our study provide evidence that cTIA-1 has a role in canonical SG formation in chicken cells and tissues. Our results also indicate that cPRD is necessary for SG aggregation.

Effect of Baihu Guizhi decoction on characteristic methylation genes expression of pyretic arthralgia rat model / 中国中药杂志

To investigate the characteristic methylation genes of pyretic arthralgia model in hot and dampness environment and the regulation effect of Baihu Guizhi decoction on this characteristic methylation genes. Plantar injection of CFA was used in hot and dampness environment to induce the pyretic arthralgia rat models. From 15th day after modeling, Baihu Guizhi decoction was given for 30 days. Foot volume was detected every 4 days after modeling, and HE staining was used to detect the histopathology of all rats' ankle joint at day 45.MeDIP-Seq sequencing method was used to detect the methylation level of knee joint synovial, and the method of difference sets was used to screen the characteristic methylation genesinpyretic arthralgia models.The contents of IL-1β, IL-17, TNF-α, EGF, IL-12p70, IL-4, IL-6 and IFN-γ in serum were measured by using suspension chips. The mRNA expression level of characteristic methylation genes was measured by qRT-PCR. The results suggested that as compared with adjuvant arthritis rat models(AA), the foot swelling and histopathology inpyretic arthralgia models (PA) were only slightly increased. As compared with normal group (NG), the wholegenome CpG island in both AA and PA groups was kept in a lower methylation state, furthermore, the methylation level was lowest in PA group; with 705 difference methylation genes in AA group and 2 418 difference methylation genes in PA group. As compared with AA, there were 1 287 difference methylation genes, including 974 down-regulated methylation genesand 313 up-regulated methylation genes. This difference methylation genes were mostly enriched in 32 KEGG pathways. Moreover, there were 52 characteristic methylation genes of PA models in promoter region, including 36 down-regulatedmethylation genes and 16 up-regulatedmethylation genes. After drug intervention, Baihu Guizhi decoction improved the foot swelling and pathological injury in PA models, significantly decreased the levels of IL-1β, TNF-α, EGF, VEGF, IL-17, IL-12p70, inhibited the mRNA expression levels of down-regulated methylation genes AHCY and RPL3, and promoted the mRNA expression levels of up-regulated methylation gene Agxt. In conclusion, unique methylation changes of synovial genes were present in PA models, and Baihu Guizhi decoction may adjust the methylation level of PA's characteristic methylation genes to achieve the therapeutic effect of pyretic arthralgia.

Tongluo Xingnao Effervescent Tablets ameliorates cognitive function of SAMP8 mice via Nampt/SIRT1/FOXO3 pathway / 中成药

AIM To investigate the effects of Tongluo Xingnao Effervescent Tablets (Chuanxiong Rhizoma,Angelicae sinensis Radix and Scutellariae Radix) on the learning and memory function in SAMP8 mice,and improvements in cognitive function.METHODS Morris water maze was used to evaluate the change of cognitive function in SAMP8 mice after they were treated with Tongluo Xingnao Effervescent Tablets for 60 d,and the activity of superoxide dismutase (SOD),the concentration of protein carbonyls (PC),the ratio of NAD +/NADH in brain tissue were detected by ELISA,the expression of Nampt,SIRT1 and FOXO3 in hippocampus were measured with immunohistochemical methods.RESULTS Tongluo Xingnao Effervescent Tablets shortened escape latency and obviously increased percentage of time in target quadrant in hidden platform test and increased the times entering the target quadrant in spatial probe test in SAMP8 mice.It evidently enhanced the activity of SOD,the ratio of NAD +/NADH and distinctly decreased the protein carbonyls level.Moreover,Tongluo Xingnao Effervescent Tablets could markedly up-regulate the expression of Nampt and SIRT1,but evidently down-regulate FOXO3 protein expression.CONCLUSION The experimental data show that Tongluo Xingnao Effervescent Tablets can enhance the cognitive function of SAMP8 through regulating Nampt/SIRT1/FOXO3 signal pathway.

Effects of Qibao Meiran Oral Liquid on SOD activity and carbonyl protein content in brain tissue of mice / 中成药

AIM To observe the effects of Qibao Meiran Oral Liquid (Polygoni multiflori Radix Praeparata,Angelicae sinensis Radix,Psoraleae Fructus,etc.) on learning and memory function,hippocampus tissue pathological morphology,SOD activity and carbonyl protein content in SAMP8 mice.METHODS Twenty-seven SAMP8 mice were randomly and equally divided into model control group,donepezil hydrochloride group and Qibao Meiran Oral Liquid group.Another nine SAMR1 mice were selected as normal control group.Mice were given successive intragastric administration for 60 days.On the 56th day,the passive avoidance test was adopted,and the learning and memory capacities were determined after 5 d;The pathological morphology was observed by HE staining;ELISA assay was used to detect the activity of SOD and the content of carbonyl protein in brain tissue.RESULTS Compared with the model control group,the escape latency of mice in the Qibao Meiran Oral Liquid group was significantly prolonged,and the number of errors decreased significantly (P ＜0.01);the pathological morphology of hippocampus tissue was significantly improved;SOD activity increased significantly,and carbonyl protein content decreased significantly (P ＜ 0.01).CONCLUSION Qibao Meiran Oral Liquid can not only improve the learning and memory function of SAMP8 mice,but also reduce the degree of hippocampus tissue degenerative disease.

Upregulation of cystathionine β-synthetase in the arcuate nucleus produces pain hypersensitivity via PKC upregulation and GluN2B phosphorylation in rats with chronic pancreatitis / 生理学报

Hydrogen sulfide (HS) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of HS and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Western blot analysis was performed to detect protein expression in the ARC. CP markedly upregulated cystathionine β-synthetase (CBS) expression but did not alter cystathionine-γ-lyase level in the ARC at 4 weeks after TNBS injection. Although the expression of total GluN2B was not altered, CP greatly enhanced the phosphorylation level of GluN2B in the ARC when compared with age- and sex-matched control rats. CP also significantly increased expression of protein kinase Cγ (PKCγ) in the ARC. Arcuate microinjection of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA, an inhibitor of CBS) significantly attenuated abdominal pain in CP rats in a dose-dependent manner and reversed the CP-induced upregulation of p-GluN2B and PKCγ in the ARC. Furthermore, the GluN2B inhibitor or specific PKC inhibitor chelerythrine significantly attenuated abdominal hyperalgesia in CP rats. The p-GluN2B expression was also suppressed by PKC inhibitor. Taken together, our results suggest that the upregulation of CBS in the ARC leads to an activation of GluN2B via PKCγ, which may play an important role in generation of pain hypersensitivity of CP.

Feasibility of umbilical cord blood stem cell transplantation for the treatment of diabetic lower limb ischemia / 中国组织工程研究

BACKGROUND:Diabetic lower limb ischemia is prone to involve distal lower limb arteries, and a conventional treatment is often unable to obtain the ideal effect. OBJECTIVE:To investigate the effect and safety of umbilical cord blood stem cel transplantation in the treatment of diabetic lower limb ischemia. METHODS: A diabetic rat model of lower limb ischemia was established, and along the femoral artery, five points were selected for injection of human umbilical cord mesenchymal stem cel suspension, 20 μL per point. At 1, 2, 4 weeks after transplantation, transcutaneous oxygen pressure, vascular density and vascular endothelial growth factor level in the ischemic region, and incidence of adverse reactions were recorded. RESULTS AND CONCLUSION:At 1, 2 and 4 weeks after transplantation, the transcutaneous oxygen pressure, vascular density and vascular endothelial growth factor level in the ischemic region were found increasing, which were significantly different from those before transplantation (P < 0.05). At different time after transplantation, al animals had no inflammatory reactions such as skin bleeding and dermatitis, and local red, sweling, hot, pain, and had no tumor-like growth in organs. These findings indicate that umbilical cord blood stem cel transplantation can safely and significantly improve symptoms of diabetic lower limb ischemia, which has certain application feasibility. Cite this article:Xie LH, Xing L, Zheng H. Feasibility of umbilical cord blood stem cel transplantation for the treatment of diabetic lower limb ischemia. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):78-82.

Acute Effects of Transforming Growth Factor-β1 on Neuronal Excitability and Involvement in the Pain of Rats with Chronic Pancreatitis

BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.

Effects of Tongluoxingnao effervescent tablet on Aβmetabolism in transgenic cell model / 中国药理学通报

Aim Tongluoxingnao effervescent tablets ( TLXNET) ,based on the ancient formula of QiongGui Tang, can improve cognitive dysfunction in different AD models. This research is aimed to study the effects of TLXNET on the Aβmetabolism and explore the anti-AD mechanism in SH-SY5 Y-APP and SH-SY5 Y-C99 cells. Methods Cells were incubated for 48h in dif-ferent concentrations of medicated serum ( containing 0% ~40% of TLXNET in the serum ) . Firstly, the non-toxic concentration was measured by MTT assay, the activity of cells was detected by LDH methods, and ELISA was used to measure the levels of Aβ1-40 and Aβ1-42 . Then, the gene and protein expressions of APP were detected via RT-PCR and Western blot of which the expressions of shearing fragments such as sAPPα and sAPPβ were investigated by Western blot, the same as the expressions of IDE and NEP. Addi-tionally, the level of mRNA, protein and activity of BACE1 were measured by qRT-PCR, Western blot and fluorescence detection kits respectively. Eventually, MTT assay was performed to detect the cell viability after the SH - SY 5 Y cells were treated with various concentrations of medicated serum and Aβ25-35 for 48h. Results There was no significant toxicity of TLXNET medicated serum in SH-SY5 Y-APP and SH-SY5 Y-C99 cells ( P >0 . 05 ) . TLXNET could signifi-cantly inhibit Aβ secretion in SH-SY5 Y-APP cells ( P0. 05). Additionally, TLXNET could still notably inhibit the expression of sAPPβ pro-tein in a dose-dependent way, with statistical signifi-cance ( P <0. 05 ) . Meanwhile, the level of mRNA, protein and activity of BACE1 were also significantly decreased by TLXNET (P <0. 01). Moreover, the medicated serum of TLXNET had a protective effect on SH-SY5 Y apoptosis induced by Aβ25-35 ( P <0 . 01 ) . Conclusion TLXNET could obviously inhibit β-secretase enzyme, and has an antagonistic effect a-gainst Aβneurotoxicity, which suggests that the inhibi-tion of β-secretase enzyme and antagonism against Aβneurotoxicity are the main anti-AD mechanism of TLX-NET .

Clinical Observation of Zishen Jianpi Huoxue Decoction Combined with Xiaoxintong Capsule in the Treat-ment of Type 2 Diabetes Complicating with Silent Myocardial Ischemia / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Zishen jianpi huoxue decoction combined with Xiaoxintong capsule in the treatment of type 2 diabetes complicating with silent myocardial ischemia (SMI). METHODS:126 patients with type 2 diabetes complicating with SMI were selected and randomly divided into control group(62 case)and observation group(64 cases). Both group were given diet guidance and hypoglycemic drugs as sulfonylureas,biguanides. Control group was given Xiaox-intong capsule 10 mg,tid;observation group was additionally given Zishen jianpi huoxue decoction 400-500 ml,bid. Both groups received treatment for 7 d. Therapeutic efficacy of thoracic obstruction,improvement of coronary artery branch stenosis and times and duration of electrocardiogram ST segment low voltage outlet were observed in 2 groups. ADR was compared between 2 groups. RESULTS:Therapeutic efficacy of thoracic obstruction and improvement of coronary artery branch stenosis in observation group were significantly better than in control group,with statistical significance(P<0.05);the times and duration of electrocardiogram ST segment low voltage outlet in observation group were significantly lesser shorter than in control group,with statistical signifi-cance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Zishen jianpi huoxue decoction complicating with Xiaoxintong capsule shows significantly therapeutic efficacy in the treatment of type 2 diabetes complicating with SMI with good safety.

Granzyme B-VEGF receptor-binding peptide fusion protein expressed in B. longum induces apoptosis of KDR-positive cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To express granzyme B-vascular endothelial growth factor (VEGF) receptor-binding peptide (GrB-VRB) fusion protein in Bifidobacteria longum (B. longum) and investigate the effects of this fusion protein on the proliferation and apoptosis of cells expressing VEGF receptor II, the kinase domain receptor (KDR).</p><p><b>METHODS</b>The recombinant expression vectors pBBADx-VRB, pBBADx-GrB and pBBADx-GrB-VRB were separately transformed into B. longum cells by electroporation. The expressed products were identified by enzyme-linked immunosorbent assay and Western blotting, and their effects on KDR-positive cells were analyzed using proliferation assay and TUNEL assay.</p><p><b>RESULTS</b>The expressed products were detected in both the supernatant and cellular fractions of B. longum cells. The recombinant GrB-VRB fusion protein reacted with such KDR-positive cells as human umbilical vein endothelial cells (HUVEC) and mouse colon cancer cell line CT-26, and caused obvious cell proliferation inhibition, cytotoxicity and cell apoptosis in these cells.</p><p><b>CONCLUSION</b>The recombinant GrB-VRB fusion protein secreted by the engineered B. longum cells can induce KDR-positive cell death as the result of GrB-induced cell apoptosis following the cell recognition by VRB.</p>

Value of (18)F-FDG PET/CT in the diagnosis of laryngeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the clinical value of (18)F-FDGPET/CT in the diagnosis of larynx carcinoma. Methods Forty-seven patients with larynx carcinoma or suspected larynx carcinoma underwent (18)F-FDG PET/CT examination within a week before therapy. The value of (18)F-FDG PET/CT in the diagnosis and staging of the malignancy was compared with that of unenhanced contrast CT.</p><p><b>METHODS</b>Forty-seven patients with larynx carcinoma or suspected larynx carcinoma underwent (18)F-FDG PET/CT examination within a week before therapy. The value of (18)F-FDG PET/CT in the diagnosis and staging of the malignancy was compared with that of unenhanced contrast CT.</p><p><b>RESULTS</b>Among the 47 patients, a definite diagnosis of larynx carcinomas was established pathologically in 43 patients. For detection of primary tumors, the sensitivity, specificity and accuracy of (18)F-FDG PET/CT were 95.3%, 75% and 93.6%, as compared with 74.4%, 50%, and 72.3% with unenhanced contrast CT scan, respectively, showing significant differences in the diagnostic sensitivity and accuracy between the two modalities (Χ=7.340, P=0.007; Χ=7.532, P=0.006). Twenty-six of the 43 patients were identified to have lymph node metastasis, for which (18)F-FDG PET/CT showed a significantly higher diagnostic sensitivity than unenhanced contrast CT (92.3% vs 61.5%, Χ=6.933, P=0.008). In the 46 excised lymph nodes from 19 patients, 26 were found positive for metastasis, for which (18)F-FDG PET/CT showed a diagnostic sensitivity of 92%, significant higher than that with unenhanced contrast CT (64%, Χ=5.71, P=0.017). PET/CT detected synchronous tumor in one case. (18)F-FDG PET/CT resulted in a change of staging in 34.9% of the patients, including upstaging in 14 patients and down-staging in one patient.</p><p><b>CONCLUSION</b>(18)F-FDG PET/CT can be an important means for diagnosis and initial staging of larynx carcinoma.</p>