Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Cost-effectiveness analyses of denosumab for osteoporosis: a systematic review.

This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the quality of pharmacoeconomic studies in osteoporosis. INTRODUCTION: There are many pharmacoeconomic studies on denosumab for osteoporosis. However, the corresponding reviews are outdated or incomplete and need to be updated and refined. This article aims to systematically review and evaluate all retrievable pharmacoeconomic studies of denosumab for osteoporosis. METHODS: A systematic literature search was performed utilizing PubMed, EMBASE(Ovid), Proquest(EconLit), Chongqing VIP, WanFang Database, and Chinese National Knowledge Infrastructure to identify full-text articles published before September 2021. The quality of full-text articles was evaluated by the Consolidated Health Economic Evaluation Reporting Standards(CHEERS) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation guideline(ESCEO-IOF). RESULTS: In total, 21 full-text articles were eligible for inclusion. Denosumab for postmenopausal osteoporosis was not dominant compared to zoledronate and teriparatide. However, denosumab was dominant compared with strontium ranelate, raloxifene, and ibandronate in patients over 65 years. The probabilities of denosumab being cost-effective or dominant were more than 85% compared with no treatment and risedronate in patients aged over 70 years. Compared to alendronate, the highest rate of denosumab dominance occurred in patients aged 65 to 75 years, at about 65%. Most of the articles had higher CHEERS scores than ESCEO-IOF scores (converted into percentages). CONCLUSIONS: The cost-effectiveness of denosumab for the treatment of osteoporosis was influenced by multiple factors. Generally, denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the transparency, generalization, and quality of pharmacoeconomic studies in osteoporosis.

Secukinumab shows high and sustained efficacy in nail psoriasis: 2.5-year results from the randomized placebo-controlled TRANSFIGURE study.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. OBJECTIVES: To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis. METHODS: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. RESULTS: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73·3% and -63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52·4% and -18·1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2·5 years, reporting a decrease in pain and discomfort. No new safety findings were observed. CONCLUSIONS: Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2·5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.

Sustained efficacy of secukinumab in patients with moderate-to-severe palmoplantar psoriasis: 2·5-year results from GESTURE, a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Secukinumab has shown sustained efficacy and safety in several manifestations of psoriasis. OBJECTIVES: GESTURE investigated the long-term (2·5-year) safety and efficacy of 150 mg and 300 mg subcutaneous secukinumab in 205 patients with moderate-to-severe palmoplantar psoriasis. METHODS: GESTURE was a randomized, double-blind, placebo-controlled, multicentre, phase IIIb trial conducted across 15 countries. The study was 140 weeks long and consisted of four periods: screening (up to 4 weeks), treatment period 1 (16 weeks), treatment period 2 (116 weeks) and post-treatment follow-up (8 weeks). Eligible patients were aged ≥ 18 years with moderate-to-severe palmoplantar psoriasis and at least one plaque outside of the palms and soles. Efficacy was assessed via a palmoplantar Investigator's Global Assessment (ppIGA) and the palmoplantar Psoriasis Area and Severity Index (PASI). RESULTS: The primary end point, a ppIGA score of 0 or 1, was met at week 16. The effect was sustained over 2·5 years with 59% [95% confidence interval (CI) 43·5-74·1] and 53% (95% CI 35·1-69·6) of patients in the secukinumab 300 mg and 150 mg groups, respectively, achieving clear or almost clear palms and soles (ppIGA 0 or 1). At 2·5 years, the mean palmoplantar PASI percentage was reduced in both the secukinumab 300 mg group (-74·7%) and the secukinumab 150 mg group (-61·6%). A total of 17% (secukinumab 300 mg group) and 18% (secukinumab 150 mg group) of patients experienced no difficulty in hands and feet functionality, as indicated by the palmoplantar quality of life instrument overall scores. The safety profile was favourable. CONCLUSIONS: GESTURE revealed that secukinumab provides a strong and sustained response over 2·5 years in challenging-to-treat palmoplantar psoriasis.

[Compound matrine injection reduces morphine tolerance of the mice with lung cancer by inhibiting expression of multidrug resistance gene 1 and P-glycoprotein].

Objective: To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp). Methods: A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA). Results: The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group (P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group (P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group (P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB (P>0.05). Conclusion: Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

Effect of secukinumab on the clinical activity and disease burden of nail psoriasis: 32-week results from the randomized placebo-controlled TRANSFIGURE trial.

BACKGROUND: Nail psoriasis is associated with functional impairment, pain and reduced quality of life. OBJECTIVES: To demonstrate the superiority of secukinumab over placebo in clearing nail psoriasis as assessed by the Nail Psoriasis Severity Index (NAPSI) at week 16 and over time up to week 132. Presented here is the week 32 interim analysis. Impact on quality of life was assessed by Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) patient questionnaires. METHODS: TRANSFIGURE is a double-blind, randomized, placebo-controlled study in patients with moderate-to-severe plaque and nail psoriasis. RESULTS: The primary objective of this study was met: both doses of secukinumab were superior to placebo at week 16 (NAPSI improvements of -45·3%, -37·9% and -10·8% for secukinumab 300 mg and 150 mg and placebo, respectively, P < 0·001). Significant improvements were seen in patients' quality of life: the NAPPA-Quality of Life total score median decreases at week 16 were 60·9%, 49·9% and 15·8% for secukinumab 300 mg and 150 mg and placebo, respectively (P < 0·001). Improvement in nail psoriasis continued to week 32: NAPSI percentage change reached -63·2% and -52·6% for secukinumab 300 mg and 150 mg, respectively. Skin clearance measured by ≥ 90% improvement in Psoriasis Area and Severity Index was significant (rates of 72·5%, 54·0% and 1·7% for secukinumab 300 mg and 150 mg and placebo at week 16, respectively, P < 0·001) and was sustained to week 32. The most common adverse events were nasopharyngitis, headache and upper respiratory tract infections. CONCLUSIONS: Secukinumab demonstrated significant and clinically meaningful efficacy and quality-of-life improvements for patients with nail psoriasis up to week 32. What's already known about this topic? Nail psoriasis is understudied and there is a lack of effective treatment options. Nail psoriasis is correlated with more severe psoriatic disease and the development of psoriatic arthritis. What does this study add? TRANSFIGURE is one of the few prospective placebo-controlled trials specifically in nail psoriasis and includes nail-specific quality-of-life measures such as Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA)-Quality of Life and NAPPA-Patient Benefit Index. In this trial, secukinumab demonstrates significant efficacy and quality-of-life improvements in this difficult-to-treat population.

[Molecular analysis of gene mutations in eight patients with Glanzmann's thrombasthenia].

Objective: To analyze the gene sequencing in eight patients with Glanzmann's thromboasthenia(GT), and combined with clinical manifestations and laboratory findings to investigate the molecular mechanism of GT. Methods: Eight patients who were diagnosed as GT based on platelet aggregation test and flow cytometry were enrolled, as well as 4 pedigrees. Next-generation sequencing was used to analyze all the exons and flanking sequences of αⅡ band ß3 gene and also platelet-type bleeding disorders related genes. Gene polymorphism was excluded by retrievaling HGMD and PubMed databases and relative literature. Mutations were confirmed by sanger sequencing. Results: All the eight patients had relatively normal platelet counts and coagulation profiles. But their platelet response to ADP was impaired, and their platelet response to ristocetin was relatively normal. Flow cytometry showed that of the 8 patients, platelet surface αⅡb/ß3 was lower than 5% of the normal value in 5 cases, and in 2 cases was 5% to 20% of normal value, and in 1 case there was no significant platelet surface αⅡb/ß3 reduction compared with normal level. Gene analysis revealed that five mutations in ITGA2B gene were identified, including c. 1750C>T(p.Arg584Ter), c.1882C>T(p.Arg628Ter), c.814G>C(p.Val272Leu), c.2333A>C(p.Gln778Pro), c.432G>A(p.Trp144Ter). Six mutations in ITGB3 gene, including c. 719G>A(p.Arg240Gln), c.2248C>T(p.Arg750Ter), c.1495T>C(p.Cys499Arg), c.1728delC(p.Ser577ProfsTer92), c.877C>T(p.Gln293Ter), c. 1260G>A were identified. In addition, mutations in genes such as RUNX1, HPS4, MYH9, ACTN1, HPS3 and SETBP1 were identified in patients with GT. Conclusions: Rather than homozygous mutations, heterozygous mutations, especially compound heterozygous mutations, are more common in patients with GT. The pathogenesis of GT may relate to gene mutations such as RUNX1 in addition to the ITGA2B gene and the ITGB3 gene.

[Analysis of the quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving pan-retinal photocoagulation].

Objective: Quality of life and the influencing factors in patients with diabetic retinopathy before and after receiving treatment of pan-retinal photocoagulation (PRP) were studied. Methods: Prospective study. A total of 55 diabetic retinopathy patients were collected at Beijing Friendship Hospital, Capital Medical University from November 2016 to August 2017 and were surveyed using Vision Function Questionaire (VFQ-25) to evaluate their quality of life before and 3 months after treatment with PRP. According to diagnostic criteria, the patients were divided into two groups: severe nonproliferative diabetic retinopathy(NPDR) and proliferative diabetic retinopathy group(PDR). SPSS was used for statistical analysis. Results: The score of VFO-25 general health before PRP treatment was 62.73±14.20, obviously lower the other sub scale scores of VFO-25. The results of variance analysis there was significant statistical difference between the composite score and the different educational levels (F=2.94, P<0.05), but there was no statistical difference for diabetes duration (F=3.01, P<0.05). The composite score was significantly significance between the severe NPDR and PDR group(t=8.95, P<0.05). The patients with hyperlipidemia (t=-3.21, P<0.05), hypertension(t=-2.32, P<0.05) and renal insufficiency(t=-2.05, P=0.045) has lower composite score. There was high relationship for age among the factors of worse logMAR vision, better logMAR vision and age (r=-0.47, P<0.05; r=-0.38, P<0.05; r=-0.26, P<0.05). The scores of VFQ-25 subscale of social function (t=-2.07, P<0.05) , role limitations (t=-2.38, P<0.05) , dependency (t=-2.99, P<0.05) and mental health (t=-2.26, P<0.05) was significantly increased after treatment of PRP. The score of ocular pain was obviously decreased (t=4.19, P<0.001) ; there were no significance in other sub scale scores. Conclusions: This study showed that the degree of visual acuity, the severity of DR and age were an important factor affecting the quality of life in DR patients. PRP therapy could improve the mental health and social field of DR patients, but failed to improve the scores of other visual functions in the patients. (Chin J Ophthalmol, 2018, 54:611-616).

Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study.

BACKGROUND: Secukinumab has demonstrated significant efficacy with a good safety profile through 1 year in plaque psoriasis. Given the chronic nature of this disease, long-term follow-up is needed to evaluate psoriasis therapies fully. OBJECTIVES: To determine the long-term (3-year) efficacy and safety of secukinumab in moderate-to-severe psoriasis. METHODS: Patients completing 52 weeks of secukinumab treatment in the SCULPTURE core study entered an extension in which they continued the same double-blind regimens. Dosing regimens included a fixed-interval schedule (FI; every 4 weeks) and retreatment as needed (RAN), in which patients were withdrawn from secukinumab and received placebo until the start of relapse, at which time secukinumab every 4 weeks was reinitiated. The study was registered with number NCT01640951. RESULTS: In total 168 patients receiving secukinumab 300 mg FI and 172 receiving secukinumab 300 mg RAN entered the extension. Secukinumab 300 mg FI sustained high efficacy: at the end of year 3, the proportion of responders achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) was 63·8%, and of PASI 100 responders it was 42·6%. The mean absolute PASI remained low (2-4) from week 52 to week 152 with 300 mg FI, with approximately two-thirds of patients reporting no impact of skin disease on their lives (Dermatology Life Quality Index of 0 or 1). Improvements in overall and subscale scores on all quality-of-life instruments were well sustained. As in the core study, FI dosing was consistently more efficacious than RAN. No new safety signals were identified to year 3. CONCLUSIONS: Secukinumab 300 mg FI sustained high responses and improved quality of life with no new safety concerns through 3 years.

Ammonia exposure affects the mRNA and protein expression levels of certain Rhesus glycoproteins in the gills of climbing perch.

The freshwater climbing perch, Anabas testudineus, is an obligate air-breathing and euryhaline teleost capable of active ammonia excretion and tolerant of high concentrations of environmental ammonia. As Rhesus glycoproteins (RhGP/Rhgp) are known to transport ammonia, this study aimed to obtain the complete cDNA coding sequences of various rhgp isoforms from the gills of A. testudineus, and to determine their mRNA and protein expression levels during 6 days of exposure to 100 mmol l-1 NH4Cl. The subcellular localization of Rhgp isoforms in the branchial epithelium was also examined in order to elucidate the type of ionocyte involved in active ammonia excretion. Four rhgp (rhag, rhbg, rhcg1 and rhcg2) had been identified from the gills of A. testudineus They had conserved amino acid residues for NH4+ binding, NH4+ deprotonation, channel gating and lining of the vestibules. Despite inwardly directed NH3 and NH4+ gradients, there were significant increases in the mRNA expression levels of the four branchial rhgp in A. testudineus at certain time points during 6 days of ammonia exposure, with significant increases in the protein abundances of Rhag and Rhcg2 on day 6. Immunofluorescence microscopy revealed a type of ammonia-inducible Na+/K+-ATPase α1c-immunoreactive ionocyte with apical Rhag and basolateral Rhcg2 in the gills of fish exposed to ammonia for 6 days. Hence, active ammonia excretion may involve NH4+ entering the ionocyte through the basolateral Rhcg2 and being excreted through the apical Rhag, driven by a transapical membrane electrical potential generated by the apical cystic fibrosis transmembrane conductance regulator Cl- channel, as suggested previously.

Cigarette Smoke and DNA Cleavage Promote Lung Inflammation and Emphysema.

Smoking-related lung diseases are among the most preventable and incurable ailments in the world. Smokers are at increased risk of developing chronic obstructive pulmonary disease that can be further complicated by emphysema and lung cancer. A subset of former smokers shows persistent lung inflammation and progressive loss of lung function, indicating a role for activation of acquired immunity in smoking-induced lung diseases. In addition to the well-established noxious effects of volatile compounds in cigarette smoke, incomplete combustion of tobacco generates nano-sized carbon black (nCB) that accumulate in lung myeloid dendritic cells and macrophages. Experimentally, intra-nasal instillation nCB can cause airway inflammation and emphysema in mice, underscoring their pathogenic role in inflammatory lung diseases. High throughput analyses of macrophages that have engulfed nCB reveal de novo activation of DNA repair enzymes, and histological studies provide evidence for DNA double-stranded breaks. Emphysematous lung myeloid dendritic cells that contain nCB express pro-inflammatory cytokines, and can efficiently differentiate naive CD4 T cells to interferon-g-secreting T helper 1 and interleukin 17A expressing cell subsets. Together these findings indicate that nCB accumulation in lung innate immune cells can initiate and sustain lung inflammation and promote emphysema development.

[The preparation and evaluation of the quality control materials for detection of platelet membrane glycoproteins by flow cytometry].

Objective: To prepare the quality control material for detection of platelet membrane glycoproteins by flowcytometry and evaluate the appearance traits, homogeneity and stability of it. Methods: Fresh platelets from the blood group O donors were fixed by the certain concentration of aldehyde solution and then washed by the imidazole buffer. After that, adding certain concentration of lyophilized protection solution into the preparations. The preparations were dispensed to be lyophilized and then were kept refrigerated in 2-8 ℃.According to the protocol of control of lyophilized biological products, the quality indicator for monitoring the prepared process, containing the appearance traits, the residual water, the platelet recovery and the rehydration quality were evaluated. The homogeneity and stability of these preparations were evaluated according to the CNAS-GL03 Guidance on evaluating the homogeneity and stability of samples used for proficiency testing and the ISO Guide 35 Reference material-general and statistical principles for certification. Results: The appearance traits and the rehydration quality of the quality control materials meeted the requirements, with the residual water distributed between 3.96% to 4.04% and the platelet recovery rate ranged from 68% to 72%.The homogeneity evaluation showed that there was no significant difference among the groups(P>0.05). The stability test indicated that the positive rate of platelet membrane glycoproteins CD42b, CD41 and CD62P of the quality control material was -0.14%, -0.14% and 0.74%, respectively, at 16 weeks after storage. There was no linear trend between the percentage of positive platelets with membrane glycoproteins and time(P>0.05). Conclusions: The quality control material for detection of platelet membrane glycoproteins by flow cytometry prepared by us meets the needs of the appearance traits, the residual water, the rehydration quality, the homogeneity and the longtime stability.It is hopeful to be used as internal quality control of the assay in clinic laboratory, the external quality assessment and proficiency evaluation.

[Comparison of two kinds of artificial tears on the dry eye after phacoemulsification].

Objective: To compare the curative effect of two different artificial tears on dry eye after phacoemulsification. Methods: Prospective randomized controlled clinical trial. From March to June in 2012, 102 patients (102 eyes) with age-related cataract were treated with phacoemulsification at Beijing Tongren Hospital, Capital University of Medical Sciences, and these eyes were randomly divided into blank group (group A ) 32 cases, treatment group 1 (group B) 35 cases and treatment group 2 (group C) 35 cases. Group A was treated with conventional antibiotics. Group B was sodium hyaluronate eye drop, group C was lipid-containing carbomer gel respectively. All patients finished a dry eye questionnaire called Ocular Surface Disease Index (OSDI), and Schimmer's test (SIt), break up time (BUT) and fluorescein staining (FL) tests were performed before surgery and at 7, 30 and 90 days after surgery respectively. Optometry were performed at 90 days after surgery. The χ(2) test was used to analyze the sex of the patients, and the age of the patients was analyzed by one-way ANOVA. Partial data in eye tests and in OSDI does not meet the normal distribution. Therefore, they were analyzed by Kruskal-Wallis H test. If significant difference existed, these data were then analyzed by independent sample Wilcoxon rank sum test. Results: Twelve patients were lost to visit within 3 months. A total of 90 patients were followed up for 90 days. The mean age of all patients was (69.5±9.5) years (46.0-89.0 years), 38 males and 64 females. There were 30 patients in Group A, group B and group C respectively. The prevalence of dry eye was 56. 7% (60/102). There was no significant difference among the three groups (P>0.05). OSDI questionnaire showed that OSDI score was significantly different among the three groups at 7, 30 and 90 days after operation (H=9.89, 55.53, 45.43, P<0.05). At 30 and 90 days after operation, the median OSDI scores were 12.50 and 10.42 in group C, respectively, which were better than those of group A scores 27.09 and 20. 8 (Z=- 6.30, -5.94, P<0.05), and were better than those of group B scores 17.71 and 13. 54 (Z=-3.40, -3.52, P<0.05). At 90 days after operation, the median BUT of B and C treatment groups was 9. 00, which was better than that of group A (4.00). The difference was statistically significant (H=21.51, P<0.05), There was no significant difference between group B and group C (Z=-0.34, P>0.05). Conclusion: The treatment of artificial tears with lipid composition in the early stage after phacoemulsification is beneficial to the improvement of postoperative symptoms and signs of dry eye. (Chin J Ophthalmol, 2017, 53: 445-450).

Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE).

BACKGROUND: Secukinumab is a fully human anti-interleukin-17A monoclonal antibody. OBJECTIVE: Determine the efficacy, safety and usability of secukinumab administered via autoinjector/pen. METHODS: This phase III trial randomized subjects with moderate to severe plaque psoriasis to secukinumab 300 mg, 150 mg or placebo self-injection once weekly to Week 4, then every 4 weeks. Co-primary end points at Week 12 were ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) and clear/almost clear skin by investigator's global assessment 2011 modified version (IGA mod 2011 0/1). Secondary end points included autoinjector usability, assessed by successful, hazard-free self-injection and subject-reported acceptability on Self-Injection Assessment Questionnaire. RESULTS: Week 12 PASI 75 and IGA mod 2011 0/1 responses were superior with secukinumab 300 mg (86.7% and 73.3%, respectively) and 150 mg (71.7% and 53.3%, respectively) vs. placebo (3.3% and 0%, respectively) (P < 0.0001 for all). All subjects successfully self-administered treatment at Week 1, without critical use-related hazards. Subject acceptability of autoinjector was high throughout 12 weeks. Adverse events were higher with secukinumab (300 mg, 70.0%; 150 mg, 63.9%) vs. placebo (54.1%), with differences largely driven by mild/moderate nasopharyngitis. CONCLUSION: Secukinumab delivered by autoinjector/pen is efficacious, well-tolerated and associated with high usability in moderate to severe plaque psoriasis.

Bionanoparticles as candidate reference materials for mobility analysis of nanoparticles.

We propose bionanoparticles as a candidate reference material for determining the mobility of nanoparticles over the range of 6 × 10(-8)-5 × 10(-6) m(2)V(-1)s(-1). Using an electrospray differential mobility analyzer (ES-DMA), we measured the empirical distribution of several bionanoparticles. All of them show monomodal distributions that are more than two times narrower than the currently used calibration particles for mobility larger than 6 × 10(-8) m(2)V(-1)s(-1) (diameters less than 60 nm). We also present a numerical method to calculate corrected distributions of bionanoparticles by separating the contribution of the diffusive transfer function. The corrected distribution is about 20% narrower than the empirical distributions. Even with the correction, the reduced width of the mobility distribution is about a factor of 2 larger than the diffusive transfer function. The additional broadening could result from the nonuniform conformation of bionanoparticles and from the presence of volatile impurities or solvent adducts. The mobilities of these investigated bionanoparticle are stable over a range of buffer concentration and molarity, with no evidence of temporal degradation over several weeks.

Variations in water use efficiency and carbon and nitrogen concentrations in red heart Chinese fir.

Temperature can significantly (P < 0.05) affect plant growth by modifying water use strategies, which are determined by intrinsic water use efficiency (WUEi). Red Heart Chinese Fir (Cunninghamia lanceolata) is one of the most important ecological and economic plantation species in China. However, the C. lanceolata water use strategy in response to increased temperatures and uneven temporal distribution of precipitation during the growing season is rarely reported. In a 7-year-old C. lanceolata plantation, differences in WUEi and C and N concentrations in different organs were analysed by anova, and the δ13C stable isotope, C, and N concentrations in stems determined at different tree heights. Stepwise regression and variance inflation factor were used to remove autocorrelated factors, and structural equation modelling was then used to explore relationships between WUEi and climate and biological factors. WUEi differed significantly between leaf and branch at different standardized precipitation evapotranspiration indices (SPEI). WUEi and N concentration decreased with age. The highest WUEi in branches and leaves were 92.7 and 88.4 µmol·mol-1 in 2020 (SPEI = 0.00), respectively. δ13C increased with relative tree height but N concentration and C/N ratio were not affected. Air temperatures has increased in between 2014 and 2020. WUEi and N concentration decreased with increasing branch and leaf age, but C concentration increased. SPEI significantly positively affected WUEi (P < 0.05), and WUEi was significantly negatively related to C concentration, which is consistent with the trade-off between C and water.

Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3. RESULTS: 51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813). CONCLUSIONS: Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.

Protective role of γδ T cells in cigarette smoke and influenza infection.

Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited γδ T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild-type mice, expressed increased IFNs, made protective influenza-specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke-exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses. Cigarette smoke induces IL-17A expression in the lungs and inhibits γδ T-cell-mediated protective anti-viral immune responses.