Interplay between diabetes mellitus and atopic dermatitis.

Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. METHODS: After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. RESULTS: Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. CONCLUSION: Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.

A multicentre randomized double-blind placebo-controlled phase III study of the efficacy and safety of xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200 mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.

Evaluation of the analytical and clinical performance of a new high-sensitivity cardiac troponin I assay: hs-cTnI (CLIA) assay.

OBJECTIVES: Cardiac troponin (cTn) is the key biomarker for diagnosis of acute coronary syndrome (ACS). We performed a complete assessment of the high-sensitivity cardiac troponin I (hs-cTnI) (CLIA) assay on the analytical performance and clinical diagnostic performance, which was compared with Abbott ARCHITECT hs-cTnI assay. METHODS: Sex-specific 99th percentile upper reference limits (URLs) were determined from a healthy population of 424 males and 408 females. High-sensitivity performance was assessed by examining the imprecision at sex-specific URLs and the detectable results above LoD in a cohort of healthy population. The diagnostic performance of the hs-cTnI (CLIA) assay was validated in a population of 934 patients with suspected ACS. RESULTS: The 99th percentile URLs were 15.3 ng/L for female, 31.3 ng/L for male and 24.2 ng/L for overall population. The total imprecision near the sex-specific 99th percentile URLs were <5 %. 76.74 % of females, 97.12 % of males and 86.69 % of overall population had cTnI values exceeding the LoD, which met the criteria of high-sensitivity troponin assay. No cross-reactivity or interference was identified. The diagnostic sensitivity, specificity, PPV, NPV, and AUC of hs-cTnI (CLIA) assay were 97.97 , 90.70, 79.02, 99.21 % and 0.9885, respectively, which were comparable to ARCHITECT hs-cTnI assay. CONCLUSIONS: hs-cTnI (CLIA) assay is a high-sensitivity troponin I method with high precision, sensitivity and specificity. The clinical diagnostic performance of hs-cTnI (CLIA) is comparable to the established ARCHITECT hs-cTnI assay. Mindray's hs-cTnI (CLIA) assay is an attractive alternative for diagnosis of myocardial infarction with a high level of accuracy and safety.

Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, placebo-controlled phase 3 trial.

BACKGROUND: Vunakizumab, a novel anti-interleukin-17A antibody, has shown promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. OBJECTIVE: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. METHODS: Six hundred ninety subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4, and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16, and every 4 weeks thereafter). The co-primary endpoints were ≥90% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. RESULTS: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%), and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P < .0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. LIMITATIONS: Chinese subjects only; no active comparator. CONCLUSION: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Preventive and Therapeutic Benefits of Natural Ingredients in Photo-Induced Epidermal Dysfunction.

BACKGROUND: The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet (UV) irradiation. UV irradiation, mainly UVB at wavelength of 280-315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. SUMMARY: While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. KEY MESSAGE: Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms.

A pilot restoration of Enhalus acoroides by transplanting dislodged rhizome fragments and its effect on the microbial diversity of submarine sediments.

Enhalus acoroides, the largest seagrass species in terms of morphology, has been observed to be declining significantly. In an effort to restore seagrass meadows, we conducted a transplantion utilizing dislodged rhizome fragments of E. acoroides as the donor materials. The growth of transplanted seagrass was monitored over a period of three years, and the impact of seagrass recolonization on sedimentary environment was assessed through analysis of sediment microbial diversity. The transplanted plants displayed notable growth, resulting in the successful recolonization of experimental plots by seagrass. The 3-year data also revealed the following findings: 1) the new shoot recruitment rate (per year) (NSR) of transplanted seagrass was 2.33 in the first year, 1.36 in the second year, and 0.83 in the third year, indicating a rapid initial growth rate of E. acoroides that subsequently slowed down; 2) the numbers of shoots and aboveground biomass of transplanted seagrass had increased by 13.0 and 15.9-fold, respectively, whereas only 3.3 and 5.3-fold increases of the natural seagrass were observed, suggesting that the transplantation of seagrass leads to a significantly accelerated recovery compared to its natural regeneration process. Furthermore, the restoration of E. acoroides resulted in a higher microbial diversity in the submarine sediments within the restoration area, as compared to the adjacent unvegetated area. This suggests that the re-vegetation of E. acoroides has a positive influence on the overall health of the sedimentary environment. This study strongly advocates for the active transplantation of dislodged E. acoroides plants resulting from human activities as a potential approach for future coastal management, specifically for the restoration of E. acoroides meadows.

Identification of novel immune subtypes and potential hub genes of patients with psoriasis.

BACKGROUND: Psoriasis is a common, chronic and relapsing immune-related inflammatory dermal disease. Patients with psoriasis suffering from the recurrences is mainly caused by immune response disorder. Thus, our study is aimed to identify novel immune subtypes and select targeted drugs for the precision therapy in different subtypes of psoriasis. METHODS: Differentially expressed genes of psoriasis were identified from the Gene Expression Omnibus database. Functional and disease enrichment were performed by Gene Set Enrichment Analysis and Disease Ontology Semantic and Enrichment analysis. Hub genes of psoriasis were selected from protein-protein interaction networks using Metascape database. The expression of hub genes was validated in human psoriasis samples by RT-qPCR and immunohistochemistry. Further, novel immune subtypes of psoriasis were identified by ConsensusClusterPlus package and its association with hub genes were calculated. Immune infiltration analysis was performed, and its candidate drugs were evaluated by Connectivity Map analysis. RESULTS: 182 differentially expressed genes of psoriasis were identified from GSE14905 cohort, in which 99 genes were significantly up-regulated and 83 genes were down-regulated. We then conducted functional and disease enrichment in up-regulated genes of psoriasis. Five potential hub genes of psoriasis were obtained, including SOD2, PGD, PPIF, GYS1 and AHCY. The high expression of hub genes was validated in human psoriasis samples. Notably, two novel immune subtypes of psoriasis were determined and defined as C1 and C2. Bioinformatic analysis showed C1 and C2 had different enrichment in immune cells. Further, candidate drugs and mechanism of action that applicable to different subtypes were evaluated. CONCLUSIONS: Our study identified two novel immune subtypes and five potential hub genes of psoriasis. These findings might give insight into the pathogenesis of psoriasis and provide effective immunotherapy regimens for the precise treatment of psoriasis.

Nighttime hypoxia effects on ATP availability for photosynthesis in seagrass.

Hypoxia is a major emerging threat to coastal ecosystems, which is closely related to the decline in seagrass meadows, but its damage mechanism is still unclear. This study found that hypoxia at night significantly reduced the photosynthetic capacity of Enhalus acoroides after reillumination. Photosystem II (PSII) was damaged by high-light stress during daytime low-tide exposure, but high-light-damaged PSII of E. acoroides could recover part of its activity indark normoxic seawater to maintain the normal operation of photosynthesis after reillumination during the next day. However, hypoxia inhibited the recovery of damaged PSII under darkness. By transcriptomic analysis and inhibitor verification experiments, dark hypoxia was shown to inhibit respiration, thereby reducing ATP production and preventing ATP from being transported into chloroplasts, which, in turn, led to an insufficient supply of energy required for PSII to recover. This study demonstrated that hypoxia has several negative impacts on the photosynthetic apparatus of E. acoroides at night reducing photosynthetic capacity after reillumination, which may be an important factor leading to the decline of the seagrass meadows.

A case of Vagococcus fluvialis isolated from the bile of a patient with calculous cholecystitis.

BACKGROUND: Chronic cholecystitis, characterized by persistent inflammation of the gallbladder, predominantly stems from the prolonged presence of gallstones. Calculous cholecystitis has demonstrated a consistent escalation in its incidence over time.Gallbladder stones have been recognized as a predisposing factor for the development of biliary tract infections.Concomitantly, there have been substantial shifts in the distribution and resistance profiles of pathogenic microorganisms responsible for biliary tract infections. The timely acquisition of bile samples for pathogen analysis is of paramount importance, given its critical role in guiding judicious clinical pharmacotherapy and enhancing patient prognosis. CASE PRESENTATION: We present a case involving a 66-year-old female patient who had previously undergone subtotal gastrectomy due to diffuse large B-cell lymphoma. The patient was admitted to our institution with complaints of abdominal pain. Subsequent diagnostic evaluation revealed concurrent choledocholithiasis and cholecystolithiasis. The patient underwent surgical cholecystectomy as the therapeutic approach. Histopathological examination of the excised gallbladder disclosed characteristic features indicative of chronic cholecystitis. Subsequent laboratory analysis of the patient's bile specimen yielded Gram-positive cocci, subsequently identified through biochemical assays, mass spectrometry, and 16 S rRNA analysis as Vagococcus fluvialis. Further in vitro antimicrobial susceptibility testing using disk diffusion and microfluidic dilution showed that this strain exhibited inhibition zone diameters ranging from 12.0 to 32.0 mm in response to 26 antibiotics, including ampicillin, cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefepime, ampicillin/sulbactam, piperacillin, ciprofloxacin, cefoperazone/sulbactam, imipenem, meropenem, piperacillin/tazobarb, penicillin, erythromycin, chloramphenicol, vancomycin, methotrexate/sulfamethoxazole, teicoplanin, linezolid, tigecycline, cefoxitin, ceftazidime, levofloxacin, minocycline and tobramycin. However, the inhibition zone diameters were 6.0 mm for amikacin, oxacillin, clindamycin, and tetracycline. The patient received ceftazidime anti-infective therapy both preoperatively and within 24 h postoperatively and was discharged successfully one week after surgery. CONCLUSION: In this study, we present the inaugural isolation and identification of Vagococcus fluvialis from bile specimens of patients afflicted with calculous cholecystitis. This novel finding lays a substantial experimental groundwork for guiding clinically rational antimicrobial therapy and advancing the exploration of relevant pathogenic mechanisms pertaining to Vagococcus fluvialis infections.

Value of Combined Detection of PCT, CRP, and FIB in Differentiating Viral Infection from Bacterial Infection in Severe Pneumonia.

BACKGROUND: The aim was to explore the value of combined detection of PCT, CRP, and FIB in differentiating severe pneumonia from viral infection and bacterial infection. METHODS: A total of 100 patients with severe pneumonia admitted to Hebei General Hospital from August 2020 to November 2021 were selected as the research objects, including 50 patients with viral pneumonia (as the viral group, n = 50) and 50 patients with bacterial pneumonia (as the bacterial group, n = 50). At the same time, the clinical data of 50 healthy people in the hospital were selected as the healthy group (n = 50). All the subjects in the three groups were tested for PCT, CRP, and FIB. The difference of each index level among the three groups was compared. The diagnostic efficacy of each index for pneumonia was analyzed by drawing receiver operating characteristic curves, and the independent predictors of pneumonia were determined by logistic regression model. RESULTS: There were no statistically significant differences in gender, age, course of disease, body mass index (BMI), and other general data among the three groups (p > 0.05). Compared with the healthy group, the levels of serum PCT, CRP, and FIB in the viral group and the bacterial group were significantly increased, and the levels of serum PCT, CRP, and FIB in the bacterial group were significantly higher than those in the viral group, and the differences were statistically significant (p < 0.05). The positive rates of FIB, CRP, and PCT in bacterial group and viral group were increased in turn, and the differences were statistically significant (p < 0.05), and the positive rates of combined detection in the two groups were significantly higher than the positive rates of single index detection (p < 0.05). Taking etiological examination as the gold standard, the sensitivity (92.59%) and specificity (90.17%) of the three combined detection methods were significantly higher than those of PCT, CRP, and FIB alone. Kappa test showed that the results of the combined detection and etiological examination were in good agreement (Kappa value = 0.847, p < 0.05). ROC curve analysis showed that the AUC of combined prediction of the three was 0.964, which was higher than that of single detection of 0.859, 0.832, and 0.871. Logistic regression analysis showed that serum PCT, CRP, and FIB were independent predictors of bacterial pneumonia, and the differences were statistically significant (p < 0.05). Pearson's correlation analysis showed that FIB level in the bacterial group was positively correlated with PCT and CRP. PCT was positively correlated with CRP. CONCLUSIONS: Compared with viral pneumonia, the levels of serum PCT, CRP, and FIB in patients with bacterial pneumonia are higher. Biochemical indexes can be used as independent predictors for the diagnosis of bacterial pneumonia, and have high diagnostic value. The combined detection of the three has the highest diagnostic efficiency, which is conducive to the clinical differential diagnosis of the early types of pneumonia infection.

Intracranial inflammatory myofibroblastic tumor: a report of two cases.

We report two cases of Intracranial inflammatory myofibroblastic tumor (IMT) with recurrent, cystic, and venous sinus occlusion. The cases show imaging progression from a small lesion (case 1) or absence of lesions (case 2). One of cases recurred 2 years after surgery and was treated with corticosteroids but the tumor was still growing and was resected again. We think the best treatment for IMT is surgical resection.

A simple model predicting in-hospital death in patients with type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (TAAAD) is a destructive cardiovascular disease, with high morbidity and mortality rates. Identifying the high-risk TAAAD patients at an early stage is urgently necessary. METHODS: A retrospective study of 160 patients was carried out. The admission data were retrospectively gathered. Logistic regression analysis and receiver operator characteristic curve (AUC) was utilized. RESULTS: Compared with the survivor group, the nonsurvivor group was older, had higher D-dimer levels, red blood cell distribution width (RDW) levels and platelet distribution width (PDW) levels, and lower fibrinogen levels, platelet levels and plateletcrit levels. Multivariate analysis displayed that four independent factors, age (hazard ratio (HR): 7.877, 95% confidence interval (CI) 2.740-22.641, p < 0.001), D-dimer (HR: 3.791, 95% CI 1.520-9.452, p = 0.004), RDW (HR: 3.300, 95% CI 1.109-9.825, p = 0.032), PDW (HR: 3.755, 95% CI 1.436-9.815, p = 0.007) were incorporated into the model. The predict accuracy of the model (AUC 0.861, 95% CI 0.798-0.911, p < 0.001) was best. CONCLUSIONS: Age, D-dimer, RDW and PDW are independent markers of in-hospital death in TAAAD patients and the newly established model has better performance in predicting high-risk patients. This model can be used as a quick screening tool to assess the prognosis of patients in individualizing.

Identification and characterization of the chemical components of Iris tectorum Maxim. and evaluation of their nitric oxide inhibitory activity.

RATIONALE: Iris tectorum Maxim. is a traditional medicinal herb that is commonly used to treat inflammatory conditions. The present study investigated the fragmentation patterns of isoflavone glycosides and their qualitative analysis. In addition, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to evaluate the anti-inflammatory properties of I. tectorum Maxim. samples collected at different time points during the year. METHODS: High-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (HPLC/QTOF-MS/MS) and HPLC with diode-array detection were employed for qualitative and quantitative analysis. The fragmentation patterns of the isoflavones were observed in negative electrospray ionization mode with collision-induced dissociation (CID). Their anti-inflammatory activity was assessed via nitric oxide (NO) production in LPS-treated RAW264.7 macrophages. RESULTS: A total of 15 chemical components were observed and tentatively identified using HPLC/QTOF-MS/MS. At low collision energy, the relative abundances of the aglycone radical anions Y0 - , [Y0 - H]-• , [Y0 - CH3 ]-• and [Y0 - H- CH2 ]-• were used for the structural characterization of tectoridin and tectorigenin-4'-O-ß-D-glucoside. The radical ions [Y0 - CH3 ]-• and [Y0 - H - 2CH3 ]-• were also employed to differentiate between iristectorin A and iristectorin B based upon their high-energy CID spectra. Levels of 9.02 mg/g of tectoridin and 1.04 mg/g of tectorigenin were found in samples collected in June, which exhibited 69.7% NO inhibitory activity. CONCLUSIONS: The characteristic fragmentation patterns enabled us to reliably identify isoflavone glycosides. The results of the quantitative determination and NO inhibitory activity offer insight into the optimal I. tectorum Maxim. harvesting time.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

MRPL35 Is Up-Regulated in Colorectal Cancer and Regulates Colorectal Cancer Cell Growth and Apoptosis.

Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial cells. Higher MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC patients. In vitro, down-regulation of MRPL35 led to increased production of reactive oxygen species (ROS) together with DNA damage, loss of cell proliferation, G2/M arrest, a decrease in mitochondrial membrane potential, apoptosis, and autophagy induction. MRPL35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse model. Furthermore, overexpression of MRPL35 or treatment of cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest, and apoptosis in vitro. These findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.

Chemical inhibition of Chlorella sp. by rotifers.

To test the hypothesis that rotifers release one or more chemical microalgal growth inhibitors in addition to devouring the microalgal cells, the effects of different concentrations of filtered, bacteria-free, rotifer culture filtrate (RCF) on the growth and physiological parameters of Chlorella sp., and the response of Chlorella sp. at different starting cell densities to 10% RCF, were studied. The results show that RCF significantly decreased Chlorella cell densities during the incubation, suggesting that rotifers release some chemical(s) that inhibit microalgal cell growth. Chlorella cell densities decreased with increasing RCF concentration. Increasing the initial cell density of Chlorella dispersed the inhibitory chemical(s) present in 10% RCF over more cells, reducing their effect. The results confirm that the action of the chemical(s) released by rotifers on microalgal cell growth was dependent on both the RCF concentration and the exposure time. They also demonstrate that ≥10% RCF significantly inhibited photosynthesis and respiration, which would account for some of the decreased Chlorella cell growth in the presence of RCF. Calculations based on the data indicate that the rotifer-derived chemical(s) released hourly from each rotifer inhibits growth by 45.5 microalgal cells in addition to the rotifer predation, with a 48 h LC50 value of 18.8% RCF. Based on these results, fresh medium instead of the old culture medium was contaminated by the rotifers.

A two-thresholds policy for a Filippov model in combating influenza.

This work designs a two-thresholds policy for a Filippov model in combating influenza, so as to estimate when and whether to take control strategies, including the media coverage, antiviral treatment of infected individuals and vaccination of susceptible population. By introducing two tolerance thresholds [Formula: see text] and [Formula: see text] of susceptible and infected individuals, the two-thresholds policy is designed as: a vaccination program is implemented when the number of susceptible individuals is above [Formula: see text]; an antiviral treatment strategy is taken and the mass media begins to report information about influenza when the infection number is larger than [Formula: see text]; no control strategies are required in other cases. Furthermore, the global dynamics of the model are analyzed by varying these two thresholds, including the existence and dynamics of sliding mode, and the existence and global stability of equilibrium. It is shown that the model solutions ultimately converge to a pseudoequilibrium or a pseudoattractor on the switching surface, or a real equilibrium. The obtained results indicate that, by choosing susceptible and infected thresholds properly, the infection number can be remained below or at an acceptable level.

Chinese Patients With Heart Valve Replacement Do Not Benefit From Warfarin Pharmacogenetic Testing on Anticoagulation Outcomes.

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry; yet, its utility in Chinese patients with heart valve replacement remains unresolved. METHODS: A total of 2264 patients who underwent heart valve replacement at Wuhan Asia Heart Hospital were enrolled in this study. Patients were randomly divided into 2 groups, namely, a genotype-guided and a traditional clinically guided warfarin dosing group. In the genotype-guided group (n = 1134), genotyping for CYP2C9 and VKORC1 (-1639 G→A) was performed using TaqMan genotyping assay. Warfarin doses were predicted with the International Warfarin Pharmacogenetics Consortium algorithm. Patients in the control group (n = 1130) were clinically guided. The primary outcome was to compare the incidence of adverse events (major bleeding and thrombotic) during a 90-day follow-up period between 2 groups. Secondary objectives were to describe effects of the pharmacogenetic intervention on the first therapeutic-target-achieving time, the stable maintenance dose, and the hospitalization days. RESULTS: A total of 2245 patients were included in the analysis. Forty-nine events occurred during follow-up. Genotype-guided dosing strategy did not result in a reduction in major bleeding (0.26% versus 0.63%; hazard ratio, 0.44; 95% confidence interval, 0.13-1.53; P = 0.20) and thrombotic events (0.89% versus 1.61%; hazard ratio, 0.56; 95% confidence interval, 0.27-1.17; P = 0.12) compared with clinical dosing group. Compared with traditional dosing, patients in the genotype-guided group reached their therapeutic international normalized ratio in a shorter time (3.8 ± 2.0 versus 4.4 ± 2.0 days, P < 0.001). There was no difference in hospitalization days (P = 0.28). CONCLUSIONS: Warfarin pharmacogenetic testing according to the International Warfarin Pharmacogenetics Consortium algorithm cannot improve anticoagulation outcomes in Chinese patients with heart valve replacement.