Stabilization of labile active ingredients in an oil-water emulsion cosmetics by freeze-drying.

BACKGROUND: Due to the instability in oil/water emulsion, certain labile active ingredients were often not used in cosmetics. OBJECTIVE: The present study has tested the effect of freeze-drying to stabilize an oil/water cosmetic emulsion. MATERIALS AND METHODS: A preliminary freeze-drying process was established at the basis of calorimetric and freeze-drying microscope studies. The stability of labile molecules in the cosmetic emulsion was evaluated at 48 degree C after freeze-drying. RESULTS: The accelerated stability experiment showed that the freeze-dried emulsion retained 90.1% vitamin C after 28 days at 48 degree C, whereas the oil-water emulsion retained only 28.3% vitamin C. The freeze-dried emulsion had significantly less oil oxidation than did the oil-water emulsion. CONCLUSION: Freeze-drying improved the stability of vitamin C and oily active ingredients in cosmetic emulsions. DOI: 10.54680/fr23210110312.

[Analysis on the allocation of human resources for chronic disease prevention and control in 664 district/county-level centers for disease control and prevention in China in 2020].

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.

Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

[Exploration of the high-risk factors of catheter-related thrombosis in breast cancer].

Objective: To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies. Methods: A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed. Results: The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old (OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC (OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein (OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position (OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level (OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions: The CRT problem can't be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

[Evaluation of the single stage treatment of intracranial or extracranial artery stenosis combined with intracranial aneurysm:experience from a single center].

Objective: To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm. Methods: The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded. Results: Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke. Conclusions: For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.

[Evaluation of intravascular therapy for cerebral ischemic tandem stenosis].

Objective: To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis. Methods: Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores. Results: Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients'mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2. Conclusion: Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

Research on function and mechanisms of a novel small molecule WG449E for hypertrophic scar.

BACKGROUND: Hypertrophic scars are complications of severe wound healing characterized by excessive fibrosis associated with aberrant function of fibroblasts. However, no available drugs can be utilized to effectively treat these scars. The transforming growth factor ß (TGFß) signalling pathway regulates collagen synthesis and plays an important role in scar formation. OBJECTIVES: To evaluate the anti-scar effects of TGFß inhibitors in vitro and in vivo. METHODS: Col1α2-luciferase reporter assay was used to screen the compounds suppress type I collagen gene transcription. Sulforhodamine B colorimetric assay and colony formation assay were used to test the compound's effect on cell proliferation. Wound healing and transwell assay were performed to test the cell migration and invasion. Western blotting, immunofluorescence, immunohistochemistry and Q-PCR assay were used to determine the protein and mRNA levels. 3D cell contraction assay was used to examine the cell contraction. Flow cytometry was performed to analyse cell apoptosis. Masson stain, H&E stain and immunochemistry were used to analyse the scar formation in vivo. RESULTS: WG449E, as one of the most potent inhibitors, was identified to significantly downregulate the mRNA and protein levels of collagen in hypertrophic scar-derived fibroblasts through inhibiting Smad2/3 phosphorylation. WG449E inhibited the proliferation, migration and contraction of fibroblasts in vitro and in vivo. In addition, WG449E induced cell apoptosis through the activation of cleaved-caspase3. Moreover, WG449E significantly attenuated hypertrophic scar formation and collagen deposition in a mechanical load-induced mouse model. CONCLUSIONS: WG449E is a potential candidate for the treatment of hypertrophic scars.WG449E downregulates the mRNA and protein levels of collagen in hypertrophic scar-derived fibroblasts through inhibiting Smad2/3 phosphorylation and nucleic localization. WG449E blocks HSF migration and invasion by regulating F-actin assignment. In addition, WG449E induces HSF apoptosis through the activation of cleaved-caspase3.

Clinical and economic burden of wound care in the tropics: a 5-year institutional population health review.

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5-year institutional population health review. Within our data analysis, wounds are broadly classified into neuro-ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound-related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound-related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1-year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years-old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1-year all-cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound-related 30-day re-admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789-17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.

[Exploration on endovascular treatment for symptomatic occlusion of the intracranial vertebral arteries in early non-acute stage].

Objective: To examine the clinical efficacy of endovascular treatment on symptomatic occlusion of intracranial vertebral artery (ICVA) in early non-acute stage. Methods: Nine consecutive patients who presented with aggressive ischemic events in the early non-acute stage of ICVA occlusion from January 2014 to December 2019 and received endovascular treatment at Department of Neurosurgery, Peking University First Hospital were retrospectively reviewed.There were 7 males and 2 females, aged 63.4 years old(range: 52 to 72 years).The average preoperative modified Rankin scale(mRS) was 4.3(range: 4 to 5), the National Institute of Health stroke scale(NIHSS) was 12.3(range: 8 to 18). Among them, 2 patients received a single stage endovascular treatment, and the other 7 patients received staged endovascular treatment.The strategy of staged treatment was as follows: firstly, the occlusion part was passed through by a micro-guidewire and dilated with balloons to maintain the blood flow above Thrombolysis In Cerebral Infarction grade 2b. Then, the intravascular large load thrombus was eliminated by the fibrinolytic system and strengthened antiplatelet drugs. After that, a second stage of angioplasty with stenting was performed on the severe residual stenosis part.The complications and the recanalization rate were collected, and the National NIHSS and mRS after endovascular treatment and in follow-up period were recorded. Results: In the 2 cases received single stage endovascular treatment, although revascularization was achieved lastly, one patient suffered embolus translocation and the other suffered re-occlusion after mechanical thrombectomy during the operation, respectively.Technical success was achieved in 6 of the 7 patients received staged endovascular treatment.On discharge, the average NIHSS scores was 5.7(range: 3 to 4) of the patients. Three months after operation,the average mRS was 1.6(range:0 to 3) and it was 0.9(range: 0 to 2) at the latest follow-up, which were better than preoperative status. Conclusions: Staged endovascular treatment might be a safe, efficient, viable option in carefully selected patients with symptomatic ICVA occlusion in early non-acute stage. It needs to be confirmed by further investigation, preferably in a large controlled setting.

Instability of brain connectivity during nonrapid eye movement sleep reflects altered properties of information integration.

Nonrapid eye movement (NREM) sleep is associated with fading consciousness in humans. Recent neuroimaging studies have demonstrated the spatiotemporal alterations of the brain functional connectivity (FC) in NREM sleep, suggesting the changes of information integration in the sleeping brain. However, the common stationarity assumption in FC does not satisfactorily explain the dynamic process of information integration during sleep. The dynamic FC (dFC) across brain networks is speculated to better reflect the time-varying information propagation during sleep. Accordingly, we conducted simultaneous EEG-fMRI recordings involving 12 healthy men during sleep and observed dFC across sleep stages using the sliding-window approach. We divided dFC into two aspects: mean dFC (dFCmean ) and variance dFC (dFCvar ). A high dFCmean indicates stable brain network integrity, whereas a high dFCvar indicates instability of information transfer within and between functional networks. For the network-based dFC, the dFCvar were negatively correlated with the dFCmean across the waking and three NREM sleep stages. As sleep deepened, the dFCmean decreased (N0~N1 > N2 > N3), whereas the dFCvar peaked during the N2 stage (N0~N1 < N3 < N2). The highest dFCvar during the N2 stage indicated the unstable synchronizations across the entire brain. In the N3 stage, the overall disrupted network integration was observed through the lowest dFCmean and elevated dFCvar, compared with N0 and N1. Conclusively, when the network specificity (dFCmean ) breaks down, the consciousness dissipates with increasing variability of information exchange (dFCvar ).

γ-Aminobutyric Acid (GABA) Induced in Vitro Differentiation of Rat Pancreatic Ductal Stem Cells into Insulin-Secreting Islet-Like Cell Clusters.

In vitro produced ß-like cells can provide promising cell therapy for curing the epidemic of diabetes. In this context, we aimed to investigate the effects of different concentrations of γ-aminobutyric acid (GABA) on the differentiation of rat pancreatic ductal epithelial-like stem cells (PDESCs) into ß-like cells. The PDESC line cells were cultured in the basal media (DMEM/F12 + 10% FBS + 1% penicillinstreptomycin) supplemented with 0 µM, 5 µM, 50 µM, 500 µM, and 5 mM of GABA for 28 days to induce their differentiation. The differentiated cells were detected by cell morphology, dithizone (DTZ) staining, immunofluorescence staining, real-time polymerase chain reaction (qPCR), and glucose-stimulated insulin secretion (GSIS) assay to validate their identity. At the end of 28 days, compared with the control group, enrichment of induced cells was high among the 5 µM, 50 µM, 500 µM, and 5 mM GABA induction groups. The formation of islet-like cell clusters (ICCs) began at 14 days, and the cell clusters showed a growth trend with the culture time. The induced ICCs were positive for DTZ staining, while the control group showed negative results for DTZ staining and the differentiated cells were also positive for ß-cell-specific markers (Ins1 and Pdx1). GSIS assay of 50 µM induction group cells at 28 days showed significantly higher levels of C-peptide and insulin secretion than the control, 5 µM, 500 µM, and 5 mM GABA-treated groups (P < 0.01). At the same time, the 50 µM induction group cells also showed significantly higher levels of Ins1, Pdx1 and Nkx6.1 mRNA as compared to the 5 µM, 500 µM and 5 mM GABA groups (P < 0.01). Thus, the addition of GABA to the basal medium effectively induced differentiation of adult rat PDESCs into insulin-secreting ß-like cells, and 50 µM was the most effective concentration for the induction.

[Microsurgical treatment of paraclinoid aneurysms].

Objective: To explore the microsurgical treatment of paraclinoid aneurysms and evaluate its safety and efficacy. Methods: The data of 21 patients with 22 paraclinoid aneurysms receiving craniotomy between Jan. 2010 and Dec. 2017 in Peking University First Hospital were retrospectively analyzed. According to the Barami K classification, 2 aneurysms were type Ⅰa, 6 type Ⅰb,7 typeⅡ,6 type Ⅲa,1 type Ⅳ. Out of the 17 cases of saccular aneurysms, 16 aneurysms were clipped and one aneurysm was trapped following high-flow EC-IC bypass. Out of the 5 cases of blood blister like aneurysms, 2 aneurysms were wrap-clipped, 2 aneurysms were trapped following high-flow EC-IC bypass and 1 aneurysm was trapped following STA-MCA bypass. The patients were reexamined with CT angiography (CTA) or digital subtraction angiography (DSA) and followed up in outpatient or by phone call. Results: Seventeen patients with 18 paraclinoid aneurysms had received aneurysm clipping. Aneurysmal neck remnant was found in 2 cases, parent artery stenosis was found in 2 cases. In all of the four bypass cases, graft artery patency was confirmed and no recurrence of aneurysm was observed. The obliteration rate of the paraclinoid aneurysm was 91%(20/22). Eight cases with preoperative vision defect had recovered to some extent. New vision defect occurred in two cases. At discharge, 12 patients scored with Glasgow outcome scale 5, 6 patients scored 4, 2 patients scored 3, and one patient scored 1. Conclusion: Microsurgical treatment for paraclinoid aneurysm is a safe and effective method with high aneurysm obliteration rate and low aneurysm recurrence rate, and is thus a reasonable and effective complementary method for endovascular treatment.

A rare case of association between Budd-Chiari syndrome and sea-blue histiocytosis.

Budd-Chiari syndrome (BCS) is a rare disease characterized by obstruction of hepatic venous outflow tract with diversified etiologies. Sea-blue histiocytosis (SBH) is a kind of storage diseases defined by the deposition of abundant sea-blue histiocytes in various organs and can lead to hepatosplenomegaly, cirrhosis, or even liver failure. The association between BCS and SBH has never been reported before. Here, we report a patient with BCS presenting with hepatosplenomegaly, portal hypertension, and pancytopenia who was later confirmed to also have SBH.

Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment.

BACKGROUND/OBJECTIVES: To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone. SUBJECTS/METHODS: Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment. RESULTS: mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ~55% and ~4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone. CONCLUSIONS: Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.192.

Protease sensitivity and redistribution of CD71 and glycophorin A on K562 cells.

Transmembrane proteins are delivered to plasma membrane from the endoplasmic reticulum and Golgi complex by vesicular transport along with the cytoskeletal network. Disruption of this process likely affects transmembrane protein expression. K562 cells were digested with Streptomyces griseus protease for different periods of time, and then re-cultured with different cytoskeletal and glycosylation inhibitors. Cell viability and surface expression of transferrin receptor (CD71) and glycophorin A (GPA) were analyzed before and after re-culture by flow cytometry. We found that digestion with protease almost completely removed extracellular CD71 and GPA but their expression recovered to the initial levels after re-culture for 8 h and 24 h, respectively. The microtubule depolymerizer colchicine promoted cell surface recovery of CD71 but inhibited that of GPA; the microtubule stabilizer paclitaxel inhibited cell surface recovery of CD71 but promoted that of GPA; the microfilament depolymerizer cytochalasin D had no effect on cell surface recovery of CD71 and GPA; the microfilament stabilizer phalloidin inhibited cell surface recovery of GPA. The glycosylation inhibitor tunicamycin inhibited the recovery of both CD71 and GPA, and BADGP inhibited the recovery of GPA. These studies show differential sensitivities of surface proteins on K562 cells to proteases, and suggest molecular mechanisms of transmembrane protein transport and cycling.

The Reliability, Validity and Responsiveness of Two Disease Scores (BPDAI and ABSIS) for Bullous Pemphigoid: Which One to Use?

A significant obstacle in guiding evidence-based management of bullous pemphigoid (BP) is the lack of a standardised, validated scoring system for the condition. The aim of this study is to evaluate the suitability of the Bullous Pemphigoid Disease Area Index (BPDAI) and the Autoimmune Bullous Skin disorder Intensity Score (ABSIS) as outcome measures for BP in clinical trials. Thirty-two BP patients were repeatedly assessed over four years using Physician Global Assessment (PGA), anti-BP180 ELISA titres, BPDAI, ABSIS, BPDAI-Pruritus, Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The reliability, validity, responsiveness, and minimal clinically important differences (MCIDs) were calculated. For inter-rater reliability, the intraclass correlation coefficients (95% CI) were: BPDAI 0.957 (0.901-0.982) and ABSIS 0.881 (0.736-0.949). Compared to ABSIS, BPDAI was better correlated with PGA(r = 0.875, p < 0.001), BPDAI-Pruritus (r=0.632, p = 0.004), ABQOL (r = 0.521, p = 0.011) and TABQOL (r=0.538, p = 0.008). MCIDs for BPDAI were 4-points for assessing clinical improvement and 3-points for deterioration. ABSIS demonstrated less responsiveness with MCIDs at 8.6-points for improvement and 4-points for deterioration. These results indicate that BPDAI demonstrated excellent reliability, validity and responsiveness, while ABSIS had moderate to good reliability, validity and responsiveness.

[Trigemino-cardiac reflex in skull base surgery].

OBJECTIVE: To explore the mechanism, clinical features, and prognosis of Trigemino-cardiac reflex (TCR) during skull base operations. METHODS: A retrospective analysis was performed on 291 patients with skull base disease from Jan. 2009 to Oct. 2015 in Peking University First Hospital. By reviewing the patients' operative data and anaesthetic electrical record, and we picked out all the patients who suffered from TCR during the operation and analyzed their surgical procedures, clinical features, influence factors, and prognosis. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. RESULTS: In all the 291 patients receiving skull base surgery, 9 patients suffering TCR for 19 times during the operation were found. These 9 cases included three acoustice schwannomas, one trigeminal schwannoma, one petroclival meningioma, one epidermoid cyst in cerebellopontine angle, one cavernous sinus cavernous hemangioma, one pituitary adenoma, and one trigeminal neuralgia. The trigger of TCR was related to manipulation, retraction, and stimulation of the trunk or branches of trigeminal nerve. The baseline heart rate was 62-119/min [mean (79.4±14.6) /min] and dropped about 29.0%-66.4% (mean 44.3%) to 22-60 /min [mean (44.2±9.6) /min] after TCR. The baseline mean arterial blood pressure was 75-103 mmHg [mean (87.5±7.8) mmHg] and dropped about 23.4%-47.2% (mean 37.3%) to 45-67 mmHg [mean (54.9±6.3) mmHg] after TCR. During the 19 times of TCR, heart rate and blood pressure could return to baseline in a short time while stopping manipulation (8 times), using atropine (8 times, dose 0.5-1.0 mg, mean 0.69 mg), using ephedrine hydrochloride (one time, 15 mg), using epinephrine (one time, 1 mg), and using dopamine (one time, 2 mg). TCR also could be triggered again by a second stimulation. There was no relative cardiologic complication or neurological deficit in the postoperative 24 hours. CONCLUSION: TCR is a short neural reflex with a drop in blood pressure and heart rate coinciding with the manipulation of the trigeminal nerve in skull base surgery. Correct recognition, intensive observation, and essential management of TCR will lead to a good prognosis.

[Effect of intermittent negative pressure on matrix metalloproteinase 9 and transforming growth factor ß of tendon-bone interface and joint fluid after reconstruction of anterior cruciate ligament in rabbits].

Objective: To study the effect of intermittent negative pressure on matrix metalloproteinase 9 (MMP)-9 and transforming growth factor ß of tendon-bone interface and joint fluid after reconstruction of anterior cruciate ligament in rabbits. Methods: A total of twenty-four New Zealand white rabbits were randomly selected hind leg of negative group, contralateral hind leg as control.Reconstruction of the anterior cruciate ligament was done by autogenous semitendinosus of rabbit.Joint of the negative pressure side placed drainage tube connecting the micro-negative pressure aspirator, and maintained an intermittent, low-intensity negative pressure.Control side placed ordinary drainage tube.Drainage tube of both sides was pulled out at the same time after 5 days.After 6 weeks, joint fluid and femur-ligament-tibia complex were obtained for study of expression of MMP-9 and TGF-ß in joint fluid and tendon-bone interface. Result: Twenty-three rabbits were included in the study because of one rabbit joint infections.Detection of joint fluid showed that MMP-9 content is significantly lower in negative group than that in the control group, and the difference is statistically significant [(8.9±1.3) pg/L vs (12.3±1.8) pg/L (P=0.002)]. TGF-ß content is significantly higher in negative group in joint fluid than that in the control group, and the difference is statistically significant [(19.0±2.2) pg/L vs (15.2±1.4) pg/L (P=0.000)]. Study of immunohistochemistry in tendon-bone interface found that expression of MMP-9 is lower in negative pressure group than that in the control group, and the difference is statistically significant (P=0.000). TGF-ß expression is significantly higher in negative group in tendon-bone interface than that in the control group, and the difference is statistically significant (P=0.000). Conclusion: Intermittent negative pressure may reduce content of MMP-9 in joint fluid and expression of MMP-9 in tendon-bone interface, increase content of TGF-ß in joint fluid and expression of TGF-ß in tendon-bone interface after reconstruction of anterior cruciate ligament in rabbits.

Association studies of genomic variants with treatment response to risperidone, clozapine, quetiapine and chlorpromazine in the Chinese Han population.

Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers. A total of 77 single-nucleotide polymorphisms of 25 genes have been investigated for four commonly used antipsychotic drugs in China: risperidone, clozapine, quetiapine, and chlorpromazine. Significant associations with treatment response for several genes, such as CYP2D6, CYP2C19, COMT, ABCB1, DRD3 and HTR2C have been verified in our study. Also, we found several new candidate genes (TNIK, RELN, NOTCH4 and SLC6A2) and combinations (haplotype rs1544325-rs5993883-rs6269-rs4818 in COMT) that are associated with treatment response to the four drugs. Also, multivariate interactions analysis demonstrated the combination of rs6269 in COMT and rs3813929 in HTR2C may work as a predictor to improve the clinical antipsychotic response. So our study is of great significance to improve current knowledge on the pharmacogenomics of schizophrenia, thus promoting the implementation of personalized medicine in schizophrenia.The Pharmacogenomics Journal advance online publication, 18 August 2015; doi:10.1038/tpj.2015.61.

Sequence analysis of peste des petits ruminants virus from ibexes in Xinjiang, China.

Peste des petits ruminants (PPR) is an infectious disease caused by peste des petits ruminants virus (PPRV). While PPR mainly affects domestic goats and sheep, it also affects wild ungulates such as ibex, blue sheep, and gazelle, although there are few reports regarding PPRV infection in wild animals. Between January 2015 and February 2015, it was found for the first time that wild ibexes died from PPRV infection in Bazhou, Xinjiang, China, where a total of 38 ibexes (including young and adult ibexes) were found to have died abnormally from PPR-related issues. First, we tested for the presence of the F gene of PPRV by RT-PCR. Then, we compared the sequence of the isolated F gene from the ibex strain, termed PPRV Xinjiang/Ibex/2015, with those previously identified from small domestic ruminants from local areas near where the reported isolate was collected as well as those from other regions. The current sequence was phylogenetically classified as a lineage IV virus, and shared a high level of sequence identity (99.7%) with a previously described Xinjiang PPRV isolate.