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Vasculopathy is an important complication of type 2 diabetes mellitus (T2DM) and the leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM), which is closely related to oxidative stress and inflammation. Haptoglobin (Hp), an acute-phase protein, binds to hemoglobin (Hb) and prevents haeme-iron oxidative damage. To investigate the distribution of the frequencies of Hp genotypes and to analyse the association between Hp gene polymorphisms and vascular complications in diabetes patients. The study included 171 patients with T2DM without vascular complications and 797 patients with T2DM with vascular complications. The clinical characteristics of the studied population were recorded. Hp genotyping was performed using polymerase chain reaction–sequence specific primers (PCR-SSP). Our results showed that the frequencies of Hp genotypes in all 968 T2DM patients were as follows: Hp1-1, 4.98%; Hp2-1, 38.07%; and Hp2-2, 56.95%. Although there was no significant difference in the Hp allele or genotype frequencies among individuals with vascular complications in the T2DM groups and controls regardless of gender, we found that the distribution of the Hp2-2 genotype and allele frequency was higher in males with diabetic retinopathy than in the control group (p

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

Objective: Based on the quality analysis of Nauclea officinalis in different growth years and different months in the same year, the most suitable harvest year and the specific month in the same year were determined according to the evaluation of the active components in the stem of medicinal parts of Nauclea officinalis. Methods: LC-MS/MS method was used to investigate the quality of Nauclea officinalis from different growth years and different months in the same year, mainly including the content determination of the active ingredients in the medicine. Results: With the prolongation of production life, the content of active ingredients in stem of Nauclea officinalis increased continuously. After reaching a certain number of years, the content of active ingredients increased little;In the middle of the same year, from mid-October to mid- June of the next year, the content of iso-vincin lactam was relatively high, especially between the end of March and the end of May. The content was high and stable, and the highest point was the stem sample collected in May. Conclusion: The content of each component in the stem of Nauclea officinalis with a growth life of more than 5 years has reached a relatively high and stable level.Nauclea officinalis with a growth life of more than 5 years should be collected as raw materials for medicinal materials. The month with high and stable content of isocyanoside lactam, namely May of each year, was taken as the best harvest time of gallbladder in one year. The best harvest time was from mid-October to mid-June of the next year, or from March to May of each year.

Yu-Xiong Guo,1,2,* Hong-Xia Ma,1– 3,* Yu-Xin Zhang,2 Zhi-Hong Chen,2 Qiong-Xiang Zhai1,2 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Pediatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong-Xiang ZhaiDepartment of Pediatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, People’s Republic of ChinaTel +86-2083827812-76222Fax +86-20-8328480Email zhaiqx_241@163.comBackground: Intellectual developmental disorders (IDD) generally refers to the persistent impairment of cognitive activities and mental retardation caused by physical damage to the brain or incomplete brain development. We aimed to explore its genetic causes.Methods: In this study, 21 IDD patients were recruited. The Gesell developmental scales (GDS) and Wechsler intelligence scale for children (WISC) were used to assess the impaired level of intellectual development for all probands. A superconducting MRI scanner (Philips AcsNT 3.0 T Philips, Best, The Netherlands) was used to perform a plain MRI scan of the skull on the probands. The whole-exome sequencing was carried out using next-generation sequencing in all probands and their families.Results: Eight had seizures and four had typical characteristics of autism. Pregnancy and delivery were uneventful except for three patients. Moderate IDD (52.4%) accounted for the majority. The abnormal MRI results included ventriculomegaly, pachygyria, broadening external cerebral space, abnormal signal change and agenesis of corpus callosum. Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASKgenes. The function areas result of gene-positive group were compared to that of gene-negative group. Not significant (p> 0.05) items were revealed after this analysis.Conclusion: Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASK genes. The function areas result of gene-positive group were not significantly different from the gene-negative group.Keywords: intellectual developmental disorders, gene variant, whole-exome sequencing

Increasing evidence indicates that exposure to inflammation during pregnancy intensifies the offspring’s cognitive impairment during aging, which might be correlated with changes in some synaptic plasticity-related proteins. In addition, an enriched environment (EE) can significantly exert a beneficial impact on cognition and synaptic plasticity. However, it is unclear whether gestational inflammation combined with postnatal EE affects the changes in cognition and synaptic plasticity-related proteins during aging. In this study, pregnant mice were intraperitoneally injected with lipopolysaccharides (LPS, 50 μg/kg) or normal saline at days 15–17 of pregnancy. At 21 days after delivery, some LPS-treated mice were randomly selected for EE treatment. At the age of 6 and 18 months, Morris water maze (MWM) and western blotting were, respectively, used to evaluate or measure the ability of spatial learning and memory and the levels of postsynaptic plasticity-related proteins in the hippocampus, including postsynaptic density protein 95 (PSD-95), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 subunit, and Homer-1b/c. The results showed that 18-month-old control mice had worse spatial learning and memory and lower levels of these synaptic plasticity-related proteins (PSD-95, GluA1, and Homer-1b/c) than the 6-month-old controls. Gestational LPS exposure exacerbated these age-related changes of cognition and synaptic proteins, but EE could alleviate the treatment effect of LPS. In addition, the performance during learning and memory periods in the MWM correlated with the hippocampal levels of PSD-95, GluA1, and Homer-1b/c. Our results suggested that gestational inflammation accelerated age-related cognitive impairment and the decline of PSD-95, GluA1, and Homer-1b/c protein expression, and postpartum EE could alleviate these changes.

The salivary glands of Panorpidae usually exhibit distinct sexual dimorphism and are closely related to the nuptial feeding behavior. In this study, the salivary glands of Neopanorpa longiprocessa were investigated using light microscopy and transmission electron microscopy. The salivary glands are tubular labial glands and consist of a scoop-shaped salivary pump, a common salivary duct, and a pair of salivary tubes. The male and female salivary glands are remarkably different in the bifurcation position of the common salivary duct and the length and shape of the secretory tubes. Compared with the simple female salivary glands, the male's are more developed as their paired elongated salivary tubes can be divided into two parts, the glabrate anterior tube and the posterior tube with many secretory tubules. The ultrastructural study shows that the male salivary tubes have strong secretory function. The existence of different secretion granules indicates that there are some chemical reactions or mixing occurring in the lumen. Based on the ultrastructural characteristics, the functions of the different regions of the salivary tube have been speculated. The relationship between the salivary glands and nuptial feeding behavior of N. longiprocessa has been briefly discussed based on the structure of the salivary glands.

AIM This study aimed to investigate the influence of single-nucleotide polymorphism in exon 26 (C3435T) of multidrug resistance 1 (MDR1) transporter gene on the concentration of methotrexate (MTX) in Chinese childhood patients with acute lymphoblastic leukemia (ALL) receiving intravenous (IV) and intrathecal (IT) high-dose methotrexate (HDMTX) chemotherapy. MATERIALS AND METHODS MDR1 C3435T polymorphism was investigated in 60 patients with Chinese childhood ALL. The study also compared the MDR1; polymorphism between the patients with Chinese childhood ALL and the published data on Americans, Mexicans, Caucasians, and Thais. The C3435T polymorphism was identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequence analysis. Cerebrospinal fluid (CSF) and plasma concentrations of MTX were measured using high-performance liquid chromatography (HPLC). MTX concentrations were compared according to MDR1 C3435T genotypes. RESULTS The frequencies of MDR1 C3435T genotype in male and female patients with Chinese childhood ALL were significantly different (p = 0.001). For the frequencies of MDR1 C3435T genotype in Hui and Han patients with Chinese childhood ALL there was no difference (p = 0.188). The distribution of allele frequencies in patients with Chinese childhood ALL was similar to the published data on Americans, Mexican, Caucasians, and Thais (p > 0.05). The CSF concentrations of MTX were found to be significantly different between the C allele (CC + CT) carriers and TT homozygous group (p = 0.04). The plasma concentrations of MTX had no significant difference between the C allele (CC + CT) carriers and TT homozygous group (p > 0.1). CONCLUSION This study showed that the polymorphism of MDR1 C3435T influenced the CSF concentration of MTX in patients with Chinese childhood ALL receiving IV and IT HDMTX treatment.

It is necessary to understand vegetation dynamics and their climatic controls for sustainable ecosystem management. This study examines the vegetation dynamics and the effect of climate change on vegetation growth in the pristine conditions of 58 woodland National Nature Reserves (NNRs) located in the upper Yangtze River basin (UYRB) in China which are little influenced by human activities. Changes in the normalized difference vegetation index (NDVI), precipitation, and temperature in the selected NNRs were observed and analyzed for the period between 1999 and 2015. The relationship between time-lag effect of climate and changes in the NDVI were assessed using Pearson correlations. The results showed three major trends. 1) The NDVI increased during the study period; this indicates an increase in the amount of green vegetation, especially due to the warmer climate during the growing season. The NDVIs in March and September were significantly affected by the temperature of the previous months. Spring temperatures increased significantly (P < 0.05) and there was a delay between climatic factors and their effect on vegetation, which depended on the previous season. In particular, the spring temperature had a delayed effect on the NDVI in summer. 2) The way in which vegetation responds to climatic factors varied significantly across the seasons. Temperature had a greater effect on the NDVI in spring and summer and the effect was greater at higher altitudes. A similar trend was observed for precipitation, except for altitudes of 1000–2000 m. 3) Temperature had a greater effect on the NDVI in spring and autumn at higher altitudes. The same trend was observed for precipitation in summer. These findings suggest that the vegetation found in NNRs in the upper reaches of the Yangtze River was in good condition between 1999 and 2015 and that the growth and development of vegetation in the region has not been adversely affected by climate change. This demonstrates the effectiveness of nature reserves in protecting regional ecology and minimizing anthropogenic effects.

Bioglycosylation is an efficient strategy to improve the biological activity and physicochemical properties of natural compounds for therapeutic drug development. In this study, two caffeic acid phenethyl ester (CAPE) glucosides (G-CAPE and 2G-CAPE) were synthesized by transglycosylation with dextransucrase from Leuconostoc mesenteroides 0326 with CAPE as an acceptor and sucrose as a donor. The products were purified and the structures were characterized. The physicochemical properties, anti-inflammatory activity, and cytotoxicity of the two CAPE glucosides were measured. The water solubility of G-CAPE and 2G-CAPE is 35 and 90 times higher, respectively, than that of CAPE. Compared to CAPE, the monoglycoside product showed superior anti-inflammatory effects, and its inhibition rate of NO, IF-6, and TNF-α is 93.4%, 76.81%, and 56.58% in RAW 264.7 macrophages, respectively, at 20 μM. Also, the cytotoxicity of both products was significantly improved. These glycosylation-modified CAPEs circumvent some of the flaws in CAPE application in anti-inflammatory drugs.

The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13% to 45%. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase inhibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC involving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor existing in neutrophils, glial cells and neurons. Increasing researches discovered that G-CSF improved cell survival in neurodegenerative diseases by its anti-inflammatory effect. However, the effect of G-CSF in suppressing inflammation in Parkinson's disease (PD) remains unclear. Thus, the purpose of this study is to explored the anti-inflammatory effect of G-CSF in mouse model of PD.G-CSF was administrated in the PD model induced by MPTP. Subsequently, the protein of tyrosine hydroxylase (TH), ionized calcium-binding adaptor molecule 1 (Iba-1) and the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the midbrain were examined. In addition, the phosphorylated mitogen-activated protein kinases (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK in the midbrain were investigated.Compared with the MPTP group, the protein of TH in the midbrain was increased, while the Iba-1 and the inflammatory factors were decreased. In addition, the expression of phosphorylated JNK (p-JNK) in the midbrain of the MPTP + G-CSF group was decreased, while the phosphorylated ERK (p-ERK) levels were elevated.These findings emphasize that G-CSF inhibited the degradation of DA neurons. The protective effect is associated with the reduction of the inflammatory factors caused by the inhibition of the microglial activation. Moreover, G-CSF may decrease the inflammatory factors through the decrease of P-JNK and the increase of P-ERK.

Objective This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. Methods A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result. Results Gallic acid was confirmed as a direct thrombin inhibitor with IC50 of 9.07 μmol/L and showed a significant inhibitory effect on thrombin induced platelet aggregation. SPR-based binding studies demonstrated that gallic acid interacted with thrombin with a KD value of 8.29 μmol/L. Molecular dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations, the calculated binding free energies was −14.61 kcal/mol. Ala230, Glu232, Ser235, Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid, providing a mechanistic basis for further optimization. Conclusion This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect, which could provide a basis for the follow-up research and development for novel thrombin inhibitors.

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

Aims To provide evidence for the clinically rational administration of bupropion (BUP), the effects of high-fat diet and CYP2B6 mutants on BUP and hydroxybupropion (HBUP) among 44 healthy Chinese subjects. Methods The concentrations of BUP and HBUP in plasma were determined with a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. Genotypes were ascertained after amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results The maximum plasma concentration (Cmax) and time to Cmax (tmax) of BUP as well as the concentration–time curve (AUC(0→96)) and Cmax of HBUP all increased by 1.18-, 1.41-, 1.38-, and 1.33-fold in the feeding group relative to the fasting group, respectively. Interestingly, the Cmax and terminal half-life (t1/2) of BUP increased by 1.33- and 1.39-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Similarly, the apparent volume of distribution (Vd) and clearance (CL) of HBUP increased by 1.38- and 1.59-fold, respectively, while the Cmax and AUC(0→96) of HBUP decreased by 1.44- and 1.49-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Concliusion These data suggest that high-fat diet and CYP2B6 mutants can influence the pharmacokinetic parameters of BUP and HBUP, thereby offering clear evidence for the rational administration of BUP among Chinese subjects in clinical settings.

Introduction: though endoscopic and percutaneous drainage have emerged as the most common minimally invasive treatments for pancreatic fluid collections (PFCs), estimates of therapeutic superiority for either treatment have yielded inconsistent results. Methods: we retrieved studies comparing the efficacy and safety of these two approaches in PubMed, Embase, and the Cochrane Library. Primary outcomes were differences in technical success, clinical success, and adverse events, and secondary outcomes included differences in reintervention, need for surgical intervention, mortality, recurrence rate, and length of hospital stay. Results: there were nonsignificant differences in technical success rate (OR 0.54; CI: 0.15-1.86), clinical success rate (OR 1.39; CI: 0.82-2.37), adverse events rate (OR 1.21; CI: 0.70-2.11), mortality rate (OR 0.81; CI: 0.30-2.16), and recurrence rate (OR 1.94; CI 0.74-5.07) between the two groups. Reintervention rate (OR 0.19; CI: 0.08-0.45) and percentage of need for surgical intervention (OR 0.08; CI: 0.02-0.39) in the endoscopic drainage group were much lower than in the percutaneous drainage group. Total length of hospital stay (standard mean difference [SMD] -0.60; CI: -0.84 to -0.36) in the endoscopic drainage group was shorter; however, there was a nonsignificant difference in the length of post-procedure hospital stay (SMD: -0.30; CI: -1.05-0.44) between the two groups. Conclusion: endoscopic drainage is effective for PFCs, and superior in terms of lower reintervention and need for surgery rates over traditional percutaneous drainage, despite a similar clinical efficacy and safety compared with traditional percutaneous drainage.

Purpose The aim of this was to discover disease‐causing gene mutations linked to genetic epilepsy with febrile seizures plus (GEFS+) in a family in the Southern Chinese Han population. Of a three‐generation pedigree of 18 members in this family, 4 were affected with GEFS+. Method Blood samples of 7 family members—3 affected and 4 unaffected individuals—were collected. Whole‐exome sequencing was performed to assess for genetic mutations in two of the affected individuals and two of the unaffected individuals. Results Fourteen potentially consequential mutations were found in the two affected individuals and were validated with the Sanger sequencing method. Blood DNA tested in polymerase chain reaction with KCNAB3 primers revealed that one novel missense mutation, c.773A>G (p.H258R) in the KCNAB3 gene, which encoded the potassium voltage‐gated channel subfamily A regulatory β subunit 3 (KCNAB3), was shared by all three affected and one unaffected family member. However, this mutation did not appear in 300 unrelated control subjects. According to the bioinformatics tools SIFT and PROVEAN, p.H258R was thought to affect protein function. Functional verification showed that the KCNAB3 mutation could accelerate the inactivation of potassium channels, thus inhibiting potassium current, increasing neuronal excitability, and promoting epileptic convulsion. Conclusions These results reveal that mutations in the KCNAB3 gene may be associated with GEFS+., A novel missense mutation in KCNAB3 was found in sufferers of a Chinese Han GEFS+ family using whole‐exome sequencing. Functional verification showed that KCNAB3 mutation could accelerate the inactivation of potassium channels, thus inhibiting potassium current, improving neuronal excitability, and promoting epileptic convulsion. It is the first report about mutation in KCNAB3 gene relating to GEFS+, and these findings may provide a new insight that mutations in the KCNAB3 gene may be the pathology of GEFS+.

BACKGROUND Bupropion (BUP) is an antidepressant and its pharmacological activity is mediated by its major metabolite, hydroxybupropion (HBUP). We investigated the effects of genetic polymorphisms of CYP2B6 on BUP and HBUP to provide certain evidence on the clinical rational administration of BUP. MATERIAL AND METHODS Plasma BUP and HBUP concentrations were assayed using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS A total of 23 healthy volunteers (eleven participants with CYP2B6*1/*1, 7 participants with CYP2B6*1/*6, 3 participants with CYP2B6*4/*6, and 2 participants with CYP2B6*1/*4) received orally administered 150 mg of BUP according to protocol. Blood samples were obtained up to 96 hours after administration. The whole blood was subject to genotyping by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The concentration-time curve (AUC(0→96)), maximum plasma concentration (Cmax), and terminal half-life (t1/2) values of BUP in CYP2B6*1/*4 were lower than those of CYP2B6*1/*1. By contrast, the time to Cmax (tmax) value of the former was higher than that of the latter. The HBUP AUC(0→96) values in CYP2B6*4/*6 and CYP2B6*1/*4 increased to values 1.12-fold and 1.98-fold, compared with CYP2B6*1/*1 carriers. However, the HBUP AUC(0→96) value in CYP2B6*1/*1 was 1.51-fold higher than that in CYP2B6*1/*6. Similarly, the HBUP Cmax values in CYP2B6*4/*6 and CYP2B6*1/*4 increased by 1.12-fold and 1.97-fold, whereas the HBUP Cmax value in CYP2B6*1/*6 decreased to a value 1.64-fold lower than that in CYP2B6*1/*1. CONCLUSIONS Genetic polymorphisms of CYP2B6 influence the pharmacokinetic parameters of BUP and HBUP and thus establish rational BUP administration for Chinese patients in clinical settings.

BACKGROUND Laparoscopic Spiegel lobectomy is difficult due to its deep location and being surrounded by gross vessels. Extrahepatic Glissonean pedicle transection method has been proposed by Takasaki during open liver resections. This approach can be successfully performed during laparoscopic anatomic hepatectomy. Here we describe pure laparoscopic Spiegel lobectomy using the extrahepatic Glissonean approach. METHODS The patient was a 25-year-old male with a background of hepatitis B. A 1.5 cm×1.7 cm mass was detected in liver Spiegel lobe and highly suspected to be an hepatocellular carcinoma. The liver function was normal (Child-pugh 5), and alpha-fetoprotein was within the normal ranges. Laparoscopic Spiegel lobectomy using extrahepatic Glissonean approach was proposed. The hilar plate was partly detached from liver parenchyma, and 2 Glissonean pedicles of the Spiegel lobe were dissected, clamped and divided. Liver parenchymal transection was performed using the harmonic scalpel. RESULTS The operation time was 196 minutes without Pringle's maneuver. Estimated blood loss was

As a widely used anticancer drug in the clinic, cisplatin has obvious side effects, especially nephrotoxicity. Previous studies have suggested that the accumulation of intracellular reactive oxygen species (ROS) is a hallmark of cisplatin-induced acute kidney injury. This study aimed to investigate the relationship between ROS accumulation induced by cisplatin and 5-HT degradation. In vivo, by HE and TUNEL staining, we found that cisplatin-induced renal lesions and apoptotic regions, which were located in proximal tubular epithelial cells, were also the regions in which tryptophan hydroxylase 1 (Tph1), aromatic l -amino acid decarboxylase (AADC), 5-HT2A receptor (5-HT2AR) and monoamine oxidase A (MAO-A) were overexpressed, as determined by immunohistochemistry. Notably, the 5-HT2AR antagonist sarpogrelate hydrochloride (SH) and the AADC inhibitor carbidopa (CDP) significantly attenuated cisplatin-induced increases in serum creatinine and blood urea nitrogen levels, renal ROS levels, oxidative stress (SOD activity and MDA), proinflammatory cytokine levels (NF-κB, TNF-α and IL-1β), proapoptotic factor levels (Bax, Bcl-2, C-caspase 3 and C-caspase 9) and the phosphorylation of p38 and STAT3, as well as renal lesions and apoptosis. The combination of SH and CDP could almost abolish the effects of cisplatin challenge. In vitro, the effects of cisplatin challenge and the inhibitory effects of SH and CDP were also observed in HK-2 cells. Additionally, similar to the combination of SH and CDP, the MAO-A inhibitor clorgyline could also abolish the effects of cisplatin challenge. More importantly, by western blotting, we detected that the upregulation of Tph1, AADC and MAO-A expression induced by cisplatin both in vivo and in vitro could be obviously suppressed by SH to decrease 5-HT synthesis and mitochondrial 5-HT degradation. Altogether, these findings suggested that cisplatin-induced nephrotoxicity is due to the activation of the 5-HT degradation system in proximal tubular epithelial cells, including 5-HT2AR and 5-HT synthesis and degradation. 5-HT2AR plays a role by mediating the expression of MAO-A and the 5-HT synthases Tph1 and AADC.

Aims To explore the relationship between renal ischemia/reperfusion injury (RIRI) and the activation of the renal 5-HT degradation system, including 5-HT2A receptor (5-HT2AR), 5-HT synthases and monoamine oxidase-A (MAO-A). Main methods Rat RIRI was induced by removing the right kidney, causing ischemia of the left kidney for 45 min and reperfusion for different times. RIRI model (ischemia for 45 min and reperfusion for 24 h) was pretreated with 5-HT2AR antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthase inhibitor carbidopa. In HK-2 cells, cellular damage was induced by hypoxia (24 h)/reoxygenation (12 h) (H/R) and treated with SH, carbidopa or the MAO-A inhibitor clorgyline. Hematoxylin-eosin, immunohistochemistry, TUNEL and fluorescent probe staining, RT-qPCR, western blotting, ELISA, etc. were used in the tests. Key findings The development of RIRI and the emergence of the RIRI peak were consistent with renal 5-HT degradation system activation. The highest expression regions of the 5-HT degradation system overlapped with those of the most severe lesions in the kidney, which were in proximal renal tubules. Rat RIRI and HK-2 cell damage, including oxidative stress, inflammation and apoptosis, could be almost abolished by synergistic inhibition of SH and carbidopa. Clorgyline also abolished the cellular damage induced by H/R. H/R–induced production of mitochondrial ROS in HK-2 cells was due to MAO-A–catalyzed 5-HT degradation, and 5-HT2AR was involved by mediating the expression of 5-HT synthases and MAO-A. Significance These findings revealed a close association between RIRI and activation of the renal 5-HT degradation system.

5-hydroxytryptamine (5-HT) is involved in the pathological processes of several liver diseases. Acute liver injury underlies the development of many liver diseases, but the mechanism remains unclear. We aimed to investigate the role of 5-HT in carbon tetrachloride (CCl4)-induced acute liver injury. Acute liver injury was induced with CCl4 (10 mg/kg) in mice pretreated with the 5-HT2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP). LO2 cells were treated with CCl4, 5-HT or 2,5-dimethoxy-4-idopametamine and pretreated with SH, CDP or the monoamine oxidase A (MAO-A) inhibitor clorgyline. Hematoxylin-eosin staining, immunohistochemistry, Real-time quantitative PCR, western blotting, fluorescent probe and biochemical markers were used to evaluate liver compromise. 5-HT2A receptor, 5-HT synthetase and MAO-A were expressed in hepatocytes; their gene and protein expression were upregulated by CCl4, which led to the degradation of mitochondrial 5-HT and overproduction of reactive oxygen species (ROS). Hepatic injury may be aggravated by ROS, which induce oxidative stress and the phosphorylation of p38 mitogen-activated protein kinase, Jun N-terminal kinase, extracellular regulated protein kinase, signal transducer and activator of transcription 3 and nuclear factor kappa-B. 5-HT2A receptor may contribute to acute liver injury by modulating 5-HT synthase and MAO-A expression. The synergistic action of SH and CDP treatment may inhibit CCl4-induced acute liver injury in a dose-dependent manner. Hence, CCl4-induced acute liver injury is due to an increase in mitochondrial ROS production caused by increased 5-HT degradation and probably involves increases in 5-HT2A receptor expression and 5-HT synthesis.

While Ag nanoparticles hold great promise for broad spectrum antibacterial activity, the potential risks of Ag nanoparticles (NPs) on human health remain a challenge. In this study, Ag/Fe3 O4 composites have been successfully prepared and characterized by transmission electron microscopy, X-ray powder diffraction, and Fourier-transform infrared spectroscopy, and their magnetic and antibacterial properties have been assessed. In vivo results show that the antibacterial effect of 500 μg/mL Ag/Fe3 O4 nanocomposites was significantly higher than that of 1000 μg/mL AgNPs after 72 h of treatment (p

The Zn2+ doped In2.77S4 (Zn–In2.77S4) photocatalyst has been synthesized via a one-step hydrothermal method. The tetracycline was adopted to measure the photocatalytic performance of the as-fabricated Zn–In2.77S4 composites. The probable photocatalytic degradation mechanism of the as-prepared composites was also discussed. Experimental results reveal that doping Zn2+ into In2.77S4 can broaden the light absorption range and improve the recycle ability as well as the separation efficiency of photo-generated electron–hole pairs of pure In2.77S4. Moreover, as the doping amount of Zn2+ increased the photocatalytic efficiency of the as-obtained Zn–In2.77S4 composites appears the tendency of firstly increasing and then decreasing. When the molar ratio of Zn2+ to In3+ is 0.04:1 (4%), in 15 min, the photocatalytic efficiency of the as-developed Zn–In2.77S4 photocatalyst reaches to the maximum of 90.0%. It is higher than 31.8% of pure In2.77S4. Furthermore, superoxide radicals and holes play major roles in the process of photodegradation tetracycline. This research can supply a promising guide to solve antibiotics pollution in water under sunlight.

Purpose This study aimed to identify disease-causing gene mutations in individuals belonging to the Southern Chinese Han population diagnosed with fever-associated seizures or epilepsy (FASE). Methods Blood samples and clinical data were collected from 78 children with FASE. All subjects were screened for mutations using whole-exome sequencing, and mutations were validated using the Sanger sequencing method. Results Three novelSCN9A heterozygous missense mutations (I775M, R429C and A442T) were noted, which are associated with febrile seizures (FS), febrile seizures plus (FS+) and genetic epilepsy with febrile seizures plus (GEFS+), respectively. The R429C and A442T mutations are located in the large cytoplasmic loop between transmembrane topological domains, whereas I775M is located in the topological domain DIIS2. The I775M and R429C mutations have highly evolutionarily conserved residues and are predicted to affect the SCN9A protein function according to bioinformatics tools. These three mutations were not identified in 300 unrelated control subjects. Conclusions Mutations in theSCN9A gene may be linked with FASE.

ObjectiveTo observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage (HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible.MethodsA total of 120 newborn SD rats aging 7 d were randomly divided into control group, model group, TPO group and G-CSF group, using the method of blockingleft carotid artery to establish HIBD model. The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment and G-CSF treatment were adopted in the model group, TPO group and G-CSF group respectively. Then 10 rats of 4 groups were executed at Day 3, 7, 14 after modeling, brain tissue was extracted to observe the brain damage; Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein (nestin) expression.ResultsInjured brain mass of model group, TPO group and G-CSF group were significantly higher than that of control group at corresponding time point (P

Progesterone (PROG) has recently been shown to have a neuroprotective effect and improve cognitive outcome in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. This study was aimed to investigate the inhibitory effects of PROG on inflammation and apoptosis in the hippocampus after TBI and its influence on the cognitive outcome. In this study, the model of TBI was established by modified Feeney's weight-dropping method. The PROG was given in a dose of 16 mg/kg by intraperitoneal injection 1 h post injury and subsequent injections subcutaneously at 6 h and 12 h after TBI. Brain samples were extracted at 24 h after trauma. The expression of COX-2 and caspase-3 was measured by immunohistochemistry and western blot technique. The cognitive outcome was assessed by Morris water maze test (MWM). The results revealed that the expression of COX-2 and caspase-3 in TBI-PROG group was distinctly less than those of the TBI group (p < 0.05). In addition, the performance of Morris water maze showed that progesterone treatment exhibited shorter latencies, more platform crossings and more time swimming in the quadrant area in the TBI + PROG rats compared to the TBI rats. In conclusion, post-TBI PROG administration may attenuate inflammation and apoptosis in the hippocampus, and this may be one of the mechanisms by which PROG improves cognitive outcome following TBI.

To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage.Sixty SD rat aged 9-12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins.The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods (P 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group (P 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group (P 0.05).Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.

Direct radical additions of ethers to terminal alkynes were investigated by using Me2Zn/O2 as radical initiator to afford 2-vinyl ether derivatives with high E-selectivity, while reversed E/Z selectivity is obtained with Et3B/O2. Two competitive pathways are suggested for the formation of vinyl radical B: zinc-radical exchange (route a) followed by protonation provides E-configuration products exclusively through Zn(II) complexation. Hydrogen abstraction by vinyl radicals (route b) yields mainly Z isomers.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The widely recognized neuroprotective effect of iron chelators is contributed by their ability to prevent reactive oxygen species (ROS) generation via the Fenton reaction, which sequesters redox-active Fe. An additional neuroprotective mechanism of iron-chelating compounds is to regulate the transcriptional activator hypoxia-inducible factor 1α (HIF-1α). In the present study, we observed that intranasal administration of deferoxamine decreased beta-amyloid (Aβ) deposition and rescued synapse loss in the brain of Aβ precursor protein and presenilin-1 (APP/PS1) double transgenic mice. We found that deferoxamine (DFO) up-regulated HIF-1α mRNA expression and its protein level, and further induced the proteins that are encoded from HIF-1-adaptive genes, including transferrin receptor (TFR), divalent metal transporter 1 (DMT1), and brain-derived neurotrophic factor (BDNF). The effects of DFO on the induction and stabilization of HIF-1α were further confirmed in vitro. This was accompanied by a decrease of Fe in the CA3 region of the hippocampus. Western blotting studies revealed that DFO differentially enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. The results suggest that the DFO may up-regulate several HIF-1-dependent neuroprotective-adaptive genes in AD via activating P38/HIF-1α pathway, which may serve as important therapeutic targets to the disease.

OBJECTIVES To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects. METHODS All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05). CONCLUSION CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

Qi Qi,1,2 Yuxin Zhang,1 Lin Shen,1 Rui Wang,1 Jiansheng Zhou,1 Hezuo Lü,1,3 Jianguo Hu1,3 1Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 2Department of Histology and Embryology, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China Purpose: Our purpose was to systematically investigate the expression pattern and role of Olig1 in neural cells during rat spinal cord development.Animals and methods: Spinal cord tissues were dissected from Sprague–Dawley rats at embryonic day 14.5 (E14.5) and E18.5, postnatal day 0 (P0), P3, P7, postnatal 2 weeks (P2W), P4W, and adults (more than 2 months after birth), respectively. The expression of Olig1 was determined by Western blot and immunostaining. To observe expression of Olig1 in different neural cell types, a double immunohistochemical staining was performed using antibodies against Olig1 with O4, ß-tubulin, glial fibrillary acidic protein (GFAP), and myelin basic protein, respectively.Results: The expression of Olig1 protein shows a significant level change in rat spinal cord at different developmental time points. Starting with E14.5, the expression gradually increased and peaked at E18.5. Olig1 decreased gradually from P3 and reached its lowest level on P7. However, interestingly, the Olig1 expression increased again from P2W, until adulthood. Olig1 was coexpressed with O4-positive oligodendrocyte progenitor cells (OPCs) and β-tubulin-positive neurons at all time points during development. Olig1 was also coexpressed transiently with GFAP-positive astrocytes at only E14.5. Olig1 was localized in the cytoplasm of O4- and β-tubulin-positive cells during the period from E14.5 to adult.Conclusion: The expression of Olig1 in OPCs and neurons at all time points during development and in astrocytes at E14.5 suggests that Olig1 may play an important role in the generation and maturation of specific neural cells during development of spinal cord. Our results contribute to understanding the mechanism underlying developmental regulation of neural cells by Olig1. Keywords: Olig1, spinal cord, development, neural cells

This study aims to investigate clinical therapeutic measures for women with urinary incontinence (UI) complicated with diabetes mellitus (DM). We performed a retrospective cohort study, including 462 female patients with UI complicated with DM (group A) and 901 patients with UI without DM (group B). Both A and B groups were divided into three subgroups according to their UI types (pure stress UI, mixed UI dominated by urge UI, and by overactive bladder syndrome) and received corresponding treatments. The subjective and objective effective rates were analyzed statistically. The overall subjective effective rates were 62.99% and 85.23% and the overall objective effective rates were 67.53% and 87.24% for groups A and groups B, respectively; the subjective and objective effective rates were 73.68% and 89.47% for group A1 (patients with pure stress UI in group A). There was no statistical difference in group A1 between subjective and objective effective rates. Unsatisfactory clinical therapeutic efficacy was observed in women with UI complicated with DM; surgical operation should be deliberated cautiously for women with SUI complicated with DM.

Accumulating evidence implicates activation (phosphorylation) of mitogen-activated protein kinases (MAPK) during nonlethal ischemic preconditioning in the protection of hippocampal CA1 neuron against subsequent ischemic events. In this paper, we undertook to identify the role of extracellular signal regulated kinase (ERK) 5 in cerebral ischemic preconditioning (CIP). Three minutes of ischemia was induced as preconditioning stimulus. Three days later, 6 min of ischemia was induced. The levels of ERK5 protein expression and its activation were detected with or without the CIP in hippocampal CA1 and the dentate gyrus (DG) regions. Our results showed that ERK5 was activated selectively in hippocampal CA1 region with, but not without, the ischemic preconditioning. Notably, during the later phase of reperfusion, the rise in ERK5 activation was strong and persistent with a peak occurring at the third day. The activation peak was effectively prevented and ERK5 protein expression was significantly decreased by intracerebroventricular infusion of ERK5 antisense oligonucleotide (every 24 h for 3 days before the preconditioning), but not by sense oligonucleotide or vehicle. Subsequently, the CA1 neuronal loss was largely elevated. Moreover, both MK801 (10 microM), an antagonist of NMDA receptor, and EGTA (100 mM, but neither 50 nor 150 mM), an extracellular Ca2+ chelator, not only effectively inhibited the ERK5 activation but also markedly abolished CIP-induced survival of the CA1 neurons. These results suggested that activation of the ERK5 pathway by CIP was at least partly dependent on moderate Ca2+ influx via NMDA receptor, which might contribute to ischemic tolerance in hippocampal CA1 region of rats.

To investigate the effects of resuscitation with three different oxygen concentrations on cerebral intra- and extra-cellular calcium, sodium and potassium changes in asphyxiated rat fetuses.Fifty-six fetal rats of gestational age of 20 days were randomly assigned into five study groups: sham operation group (control, n = 11), room-air resuscitation group (n = 10), and 3 oxygen-resuscitated groups (n = 14, 11, and 10 respectively). Different inhaled oxygen concentrations and different timings of oxygen delivery were assigned. Except for control all fetal rats were rendered ischemic and hypoxic in utero by interrupting the placental circulation. After re-circulation, intra- and extra-cellular concentrations of calcium, sodium, and potassium in the brains were measured for each individual group.The mean intracellular free calcium concentration of fetal rat brains was similar for the room-air resuscitation group (552.1 +/- 93.5 nmol/L) and the group resuscitated with 92.8% oxygen (520.6 +/- 79.1 nmol/L) and both were significantly higher than in the control (315.3 +/- 86.9 nmol/L) (P0.001). After resuscitation with 65% oxygen, be it instituted before or immediately after hypoxia, their mean intracellular free calcium concentrations in the brain cells (441.5 +/- 47.9 and 452.9 +/- 36.4 nmol/L respectively) were significantly lower than those in the room-air resuscitation (P0.01) and 92.8% oxygen group (P0.05), though still higher than in the control (P0.05). There was no difference in the total concentrations of calcium, sodium, or potassium among all groups.Resuscitation with 92.8% oxygen or room air exerted a similar effect on the parameters measured, indicating that resuscitation of asphyxiated neonates using 100% oxygen might not be superior to using room air. Resuscitation with 65% oxygen resulted in lower cerebral intracellular calcium concentrations and might produce a better outcome than using 100% oxygen or room air.

ObjectiveTo explore the protective effects of ginseng mixture on myocardial fibrosis (MF) in rats.MethodsA total of 60 Wistar rats were randomly divided into control group without modeling operation, and another 4 groups using subcutaneous injections of isopropyl adrenaline for 10 d to set up the MF model: model group with saline lavage treatment after modeling, captopril group with captopril lavage, ginseng mixture group A and group B with low and high dose mixture treatment respectively. After treatment for 14 d, abdominal aorta and myocardial tissue were extracted to observe the pathological morphological changes and heart weight index in each group.ResultsThe left ventricular weight and heart heavy index of captopril group and group B were significantly lower than that of model group and group A (P