Neo-Commissural Alignment by Withdrawing and Readvancing the Delivery System during Transcatheter Aortic Valve Replacement with Self-Expanding Prosthesis.

Objective: To investigate the feasibility of obtaining neo-commissural alignment by withdrawing and readvancing the delivery system during transcatheter aortic valve replacement (TAVR) with self-expanding prosthesis. Methods: TAVR was performed in five patients with severe aortic valve stenosis by the femoral approach. The delivery catheter was withdrawn and readvanced with the opposite orientation when the Venus-A plus transcatheter heart valve (THV) centre marker was found to be overlapped with or close to the left marker at the aortic annulus level on the fluoroscopic image at the projection of the right and left coronary cusps superimposing. Neo-commissural alignment was evaluated by comparing the aortic computed tomography before TAVR with it after TAVR. Results: The THV centre marker was overlapped with or close to the right marker at the aortic annulus level on the fluoroscopic image at the projection of the right and left coronary cusps superimposed in all the present five patients after withdrawing and readvancing the delivery system. The commissural angle deviation before vs. post TAVR was 12.3° ± 7.0°. Three of five patients had neo-commissural alignment. Two of the five patients had mild neo-commissural misalignment. Conclusions: It is possible to obtain the neo-commissural alignment by controlling delivery catheter insertion orientation using the markers on the inflow of the Venus-A plus valve.

Laser and light therapy combined with topical minoxidil for alopecia areata: a systematic review and meta-analysis of randomized controlled trials.

We aim to evaluate the clinical efficacy and safety of using laser and light combined with topical minoxidil for alopecia areata. We searched PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), VIP database, and Wanfang Data from their inception to September 18, 2022. The risk of bias of the included RCTs was assessed by the Cochrane Collaboration tool. RevMan 5.3 software and Stata 14.0 software were used to perform the statistical analysis. The GRADE system assessed the quality of evidence. Ten studies were enrolled finally. The results of the meta-analysis showed that compared with topical minoxidil alone, the 308-nm excimer laser/light or He-Ne laser combined with topical minoxidil could reduce the SALT (Severity of Alopecia Tool) score (MD= -5.88, 95% CI [-9.79, -1.98], P=0.003). Whether fractional CO2 laser (RR=1.29, 95% CI [1.14, 1.46], P<0.0001), 308-nm excimer laser/light (RR=1.32, 95% CI [1.12, 1.55], P=0.001), He-Ne laser (RR=1.69, 95% CI [1.07, 2.69], P=0.03), or NB-UVB (RR=1.35, 95% CI [1.07,1.70], P=0.01) combined with topical minoxidil may improve the treatment response rate, comparing with topical minoxidil only. The recurrence rate of laser and light combined with topical minoxidil was lower than that of the minoxidil alone group (RR=0.54, 95% CI [0.31, 0.93], P=0.03) when follow-up time was 1 year. In addition, the incidence of adverse events including irritant contact dermatitis, erythema, desquamation, pain, and pruritus was no significant difference between the two groups (RR=1.50, 95% CI [0.95, 2.36], P=0.08). The level of evidence for outcomes was classified as very low to moderate. Based on the available evidence, laser and light combined with topical minoxidil therapy may be effective and safe for alopecia areata. However, more high-quality trials are required for comprehensive analysis and further verification.

Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos.

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC-MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.

Determination of Optimal Fluoroscopic Angulations for Left Main Coronary Artery Ostial Interventions: 3-Dimensional Computed Tomography Validation.

Background: Current recommendations for the best views for the left main coronary artery (LMCA) ostium intervention are empirical. Objectives: To determine the optimal projection to visualize the LMCA ostium using only fluoroscopy. Methods: The optimal projection to visualize the LMCA ostium was determined using fluoroscopic images of superimposing the lowest points of the distal ends of two J tipped wires in the noncoronary cusp (NCC) and right coronary cusp (RCC). This was validated independently using 3-dimensional computed tomography (3D-CT) reconstruction. Results: Satisfactory images of the overlapping wires in NCC and RCC could be obtained in 90% (45/50). Between the fluoroscopic and the 3D-CT reconstruction approaches, the mean difference for NCC and RCC overlapping at horizontal axes is -1.8 with a 95% limit of agreement between -3.94 and 0.34 (p=0.10) and at vertical axes -1.6 with a 95% limit of agreement between -3.46 and 0.26 (p=0.09); and the mean difference for the optimal projection to visualize the LMCA ostium at horizontal axes is -3.22 with a 95% limit of agreement between -7.26 and 0.81 (p=0.11) and at vertical axes -2.31 with a 95% limit of agreement between -5.83 and 1.21 (p=0.09). The 3D angulation deviation for the optimal projection to visualize the LMCA ostium was 8.5° ± 4.7° when the LMCA ostium faced the NCC-RCC commissure (n = 32) and 22.3° ± 16.0° (p=0.009) when it did not (n = 13). Conclusions: The optimal projection for LMCA ostial intervention can be determined using fluoroscopic images of superimposing wires in the NCC and RCC when the LMCA ostium faces the NCC-RCC commissure, as was the case in 71% of the patients studied.

Acid-base-governed deep eutectic solvent-based microextraction combined with magnetic solid-phase extraction for determination of phenolic compounds.

A sensitive method based on the use of green deep eutectic solvents (DESs) was designed for the determination of bisphenol-A, bisphenol-AF, tetrabromobisphenol-A and 4-tert.-octylphenol followed by HPLC. This method takes advantage of magnetic solid-phase extraction purification and acid-base induced DES liquid-liquid microextraction. The Mg(II)-Al(III) layered double hydroxide-coated magnetic nanoparticles were selected to purify samples. The DESs were systematically prepared by a range of medium-chain saturated fatty acids (C8-C12) and D,L-menthol. The melting point and the extraction efficiency of phenolic compounds were adjusted by changing the carbon chain length of fatty acid in suitable proportions. Acid-base induction significantly improves the extraction efficiency. The method has lower limits of detection ranging from 6 to 11 ng L-1, good linearity (0.05-500 µg L-1) and high enrichment factors (86-91). The method was successfully applied for the determination of four phenolic compounds in beverage samples. The recoveries ranged from 84.4 to 101.3%. Graphical abstract Schematic representation of the extraction of four phenolic compounds by medium chain (C8-C12) fatty acid-based eutectic solvent (DES) through acid-base-induction.

A green deep eutectic solvents microextraction coupled with acid-base induction for extraction of trace phenolic compounds in large volume water samples.

A simple, effective and convenient method for determination of phenolic compounds by acid-base induced deep eutectic solvents (DESs) microextraction was developed. The binary and ternary DESs were prepared by a range of fatty acids (C8-C12), which can act as hydrogen bond donors and hydrogen bond acceptors simultaneously. The gas-assisted mixing customization provides excellent mixing performance and concentration efficiency through the bubble adsorption mechanism for the handling of large-volume aqueous sample. In extraction process, NH3·H2O can act as the emulsifier agent and reacted with DESs to form salts with a cloudy solution, which can obviously improve the extraction efficiency. HCl can act as the phase separation agent, and there is no need to centrifuge, which increases the efficiency of analysis procedure. The factors affected on extraction efficiency were carefully optimized. At optimum conditions and molar ratio of C8:C9:C12 (3:2:1), the limit of detections (LODs), the preconcentration factor, the repeatability (RSDs%) were in the range of 0.22-0.53 µg L-1, 235-244, and 2.6-6.7%, respectively. Finally, the proposed method was applied to analyze four phenolic compounds in real water samples and the recoveries were between 87.4% and 106.6%.

Purification and Characterisation of a Fibrinolytic Enzyme from Rhizopus microsporus var. tuberosus.

Extracellular fibrinolytic enzyme from Rhizopus microsporus var. tuberosus was purified and characterised. The microorganism was isolated in a distillery from daqu, a fermentative agent used in the production of Chinese liquor and vinegar at different temperatures. The fibrinolytic enzyme was partially purified by ammonium sulphate precipitation, dialysis, DEAE Sepharose® Fast Flow ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The molecular mass of the fibrinolytic enzyme was estimated to be 24.5 kDa by SDS-PAGE. The purified enzyme showed optimal activity at pH=7.0 and 37 °C by fibrin plate method. It showed stronger resistance to the inhibition by trypsin and was stable at 37 °C retaining 96.1% residual activity after 4 h of incubation. The fibrinolytic activity of the enzyme was enhanced by Na+, Ca2+, Mg2+ and Mn2+. Conversely, Zn2+ and Cu2+ partly inhibited enzymatic activity. Using fibrin plate method, we found that the enzyme not only degrades fibrin directly, but also activates plasminogen into plasmin to degrade fibrin. The results indicate that the pure enzyme has a potential in dissolving blood clot, and the possibility for application in the treatment of thrombosis.

Does green technology transformation alleviate corporate financial constraints? Evidence from Chinese listed firms.

Green technology transformation is crucial for China to achieve its carbon peak and carbon neutrality goals. We use green transformation keywords extracted from the annual reports of listed firms to construct a green technology transformation intensity index for enterprises and investigate the impact of green technology transformation on corporate financial constraints. Our findings indicate that green technology transformation significantly mitigates corporate financial constraints, with green subsidies and debt financing as crucial mechanisms. Moreover, this effect is particularly pronounced in high-carbon-intensity industries, firms with fewer political connections, and firms affected by the carbon trading pilot. Additionally, digital and green transformations have a synergistic effect on alleviating corporate financial constraints. Therefore, we should promote the green technology transformation of enterprises and guide green finance to serve the real economy, effectively solve the financing dilemma of green enterprises, and provide strong green kinetic energy for sustainable development.

Can enterprise green transformation inhibit accrual earnings management? Evidence from China.

This study theoretically and empirically analyzes the impact and mechanism of corporate green transformation on accrual earnings management using a sample of China's A-share listed companies from 2015 to 2021. The results indicate that the green transformation of enterprises helps restrain accrual-based earnings management, especially accrual-based earnings management, which increases profits, and that the inhibition effect of enterprise green transformation on earnings management is more significant in high-tech and growth-stage enterprises. The mechanism test shows that corporate green transformation can inhibit accrual-based earnings management by increasing analyst follow-up and easing financing constraints. Using China's environmental tax law, promulgated in 2018, as an exogenous shock to construct the PSM-DID, the conclusion still holds after alleviating endogeneity. Further research has found that green transformations can also help inhibit real earnings management. This study provides new empirical evidence for a comprehensive understanding and evaluation of the governance role of corporate green transformation and provides a reference value for further comprehensively promoting the green transformation of Chinese enterprises and improving the quality of accounting information.

Causality of unsaturated fatty acids and psoriasis a Mendelian randomization study.

Background: Many observational studies have identified a link between unsaturated fatty acids and psoriasis. However, they contain reverse causality and confounding factors, and there is no definite causal study between unsaturated fatty acids and psoriasis. Objectives: Analysis of causality between unsaturated fatty acids and psoriasis by Mendelian randomization. Methods: We used IEU Open GWAS Project, omega-3 PUFA and omega-6 PUFA data from 114,999 subjects, MUFA data from 13,535 subjects, and psoriasis data from 4,510 cases and 212,242 controls were included. We employed the inverse-variance weighted (IVW) method as the primary analytical approach and four additional MR methods. Moreover, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Q and MR-Egger intercept tests, respectively. Finally, we performed sensitivity analyses to enhance our findings' precision and veracity. Results: IVW results showed no causal effect of omega-3 PUFA on psoriasis (p = 0.334; OR, 0.909; 95% CI, 0.748-1.104), omega-6 PUFA cause psoriasis (p = 0.046; OR, 1.174; 95% CI, 1.003-1.374), MUFA cause psoriasis (p = 0.032; OR, 1.218; 95% CI, 1.018-1.457), no causal effect of omega-3 PUFA in psoriasis (p = 0.695; OR, 0.989; 95% CI, 0.937-1.044), no causal effect of omega-6 PUFA in psoriasis (p = 0.643; OR, 1.013; 95% CI, 0.960-1.068), psoriasis is not causal to MUFA (p = 0.986; OR, 1.000; 95% CI, 0.949-1.055). Heterogeneity, horizontal pleiotropy, and sensitivity analyses showed reliable results. Conclusion: We found that circulating omega-6 PUFA and MUFA cause psoriasis, while omega-3 PUFA do not. Treatments that lower circulating omega-6 PUFA and MUFA are effective in psoriasis. After a better understanding of fatty acid intake and circulation, the population can be advised to regulate their diet.

Bibliometric analysis and description of research trends in the treatment of psoriasis with biologic agents in the past two decades (2004-2023).

BACKGROUND: Biologics are essential in treating psoriasis. In recent years, the pathogenesis exploration and development of new target drugs have provided a more complete evidence-based foundation for the biological treatment of psoriasis. This study aims to use bibliometrics to analyze the research status and development trends of biologics in psoriasis. METHODS: The bibliometric analysis of publications related to biologics in psoriasis from 2004 to 2023 was conducted using the Web of Science Core Collection (WoSCC) database as the search data source. To perform the bibliometric analysis and create visual knowledge graphs, CiteSpace, the Bibliometrix R package, and VOSviewers were utilized. RESULTS: The study included a total of 3800 articles. The United States had the highest number of publications. The leading authors and institutions were Steven R. Feldman and the University of Manchester, respectively, in the global partnership. The cluster plot divided all keywords into 11 categories. Currently, Secukinumab and Guselkumab are representative biological agents being studied due to their considerable efficacy and long-term safety. CONCLUSIONS: Targeted therapy has emerged as a significant trend in the current treatment of psoriasis. Early and active use of biologics can effectively control disease progression, prevent or delay the occurrence of comorbidities, and may even alter the natural course of psoriasis. However, further investigation is required to fully understand the specific mechanisms of psoriasis and the use of biological agents.

Disseminate and Recurrent Infundibular Folliculitis: Case Report and Literature Review.

We retrospectively analyzed the clinical data of 1 case of disseminate and recurrent infundibular folliculitis (DRIF) in our hospital and 31 cases of DRIF reported in previous domestic and international studies. There were 32 cases, including 22 males and 10 females, with a mean age of onset of 24.72 ± 13.68 years. Skin lesions were more likely to occur on the trunk and proximal extremities and may involve the face, neck, and genitals. Typical histopathology revealed mild thickening and spongy edema of the spinous layer, different degrees of pigmentation increase in the basal layer, and mild to moderate spongy edema and inflammatory cell infiltration (predominantly lymphocytes and neutrophils) in the infundibulum and around the hair follicle. DRIF is a chronic disease more prevalent in young men of African descent and individuals with Fitzpatrick skin types 4-6. This disease is diagnosed based on clinical features and histopathology and is preferentially treated with retinoids.

Efficacy of fire needle combined with 308 nm excimer laser therapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitiligo is a common depigmenting skin disorder. This work is performed to systematically evaluate the efficacy and safety of fire needles combined with 308 nm excimer laser therapy in treating vitiligo. METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on fire needles combined with 308 nm excimer laser therapy with 308 nm excimer laser therapy alone for vitiligo were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes. RESULTS: In this study, 10 RCTs and 1333 patients were included. The results showed that compared with 308 nm excimer laser therapy alone, fire needle combined with 308 nm excimer laser therapy is more effective in improving clinical effective rate (RR = 1.36, 95% CI [1.24, 1.50], p < 0.00001), serum CD4+ level (MD = 3.12, 95% CI [2.50, 3.74], p < 0.00001), CD4+/CD8+ ratio (MD = 0.24, 95% CI [0.09, 0.39], p = 0.001), and quality of life measured by the Dermatology Life Quality Index (DLQI) (MD = 3.76, 95% CI [3.33, 4.19], p < 0.00001), and reducing the Vitiligo Area Score Index (VASI) (MD = -5.47, 95% CI [-6.56, -4.37], p < 0.00001). The reported adverse events, including redness, swelling, pain, blisters, and itching, were controllable, and all these events were well tolerated. CONCLUSION: The current evidence indicates that fire needle combined with 308 nm excimer laser therapy is effective and safe for vitiligo. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

Digital financial inclusion and quality of economic growth.

Recently, digital financial inclusion has experienced rapid growth, introducing transformative changes to the finance industry. Its attributes of low cost, extensive coverage, and efficient cross-temporal and spatial information dissemination have had a significant impact on both economic growth and social development. This study, using China's provincial panel data, measures the quality of economic growth based on technological innovation, coordinated development, environmental protection, opening to the outside world, and people's livelihood. It verifies the impact of digital financial inclusion on the quality of economic growth by utilizing the panel fixed effect model, mediation effect model, panel threshold model, and spatial Durbin model. Digital financial inclusion has a positive impact on the quality of economic growth, particularly in the eastern region and regions with high marketization. It can effectively promote the quality of economic growth by stimulating entrepreneurial vitality, and has had a positive and increasing non-linear effect on the quality of economic growth over the past few years. Moreover, digital financial inclusion can promote the quality of economic growth in neighboring regions. Therefore, the quality of economic growth can be significantly improved by expanding the coverage breadth and usage depth of digital financial inclusion.

Effects and safety of fire needle adjuvant chemical peels therapy in acne vulgaris: a systematic review and meta-analysis.

BACKGROUND: Acne vulgaris (AV) is a common skin disease. Fire needle is a method of quickly piercing the local skin lesions with red-hot needles for AV. This work aimed to evaluate the efficacy and safety of fire needle combined with chemical peels for AV. METHODS: Eight databases including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Internet, Wanfang, Sinomed, and VIP databases were searched to enrolled randomized controlled trials (RCTs) comparing fire needle therapy combined with chemical peels with chemical peels alone. The risk of bias was evaluated by the Cochrane Collaboration's tool. Statistical analysis was completed by RevMan 5.3 and Stata 14.0. RESULTS: Altogether 18 studies including 1213 patients were enrolled. Compared with chemical peels alone, fire needle adjuvant chemical peels therapy improved the total effective rate (RR = 1.37,95% CI [1.26,1.48], p < 0.00001) and skin lesions (MD = -2.11, 95% CI [-2.74, -1.47], p < 0.00001), and reduced the recurrence rate (RR = 0.50,95% CI [0.33,0.76], p = 0.0009).The application of fire needle was associated with few adverse reactions, all of which were well tolerated and transient. CONCLUSION: Fire needle adjuvant chemical peels therapy is effective and safe for AV. Nevertheless, more large-scale, well-designed clinical studies are warranted to provide evidence-based medical support.

Good coronary collateral circulation is not associated with better prognosis in patients with chronic total occlusion, regardless of treatment strategy.

OBJECTIVE: This study aimed to assess the effects of coronary collateral circulation (CCC) on the prognosis of patients with chronic total occlusion (CTO) under different treatment strategies. METHODS: We analyzed a total of 1124 patients who were diagnosed with CTO and divided them into groups with good CCC (grade 2 to 3, n = 539) or poor CCC (grade 0 to 1, n = 531). The primary outcome was cardiac death during follow-up; the secondary outcome was major adverse cardiovascular events (MACEs). We also performed subgroup analyses in groups with and without CTO revascularization (CTO-R and CTO-NR, respectively), and sensitivity analyses excluding patients who received failed CTO-PCI to further investigate the effect of CCC. RESULTS: During a median follow-up duration of 23 months, we did not detect any significant differences between the good CCC group and the poor CCC group in terms of cardiac death (4.2% vs 4.1%; adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.56-1.83; p = 0.970) and MACEs (23.6% vs 23.2%; adjusted HR, 1.07; 95% CI, 0.84-1.37; p = 0.590). Subgroup analyses according to CTO revascularization showed similar results. In addition, we observed no differences in sensitivity analyses when patients who received failed CTO-PCI were excluded. CONCLUSION: Good CCC was not associated with a lower risk of cardiac death or MACEs among patients with CTO, regardless of whether the patients received CTO revascularization treatment.

Effect of complete percutaneous revascularization on improving long-term outcomes of patients with chronic total occlusion and multi-vessel disease.

BACKGROUND: Limited data are available on the comparison of clinical outcomes of complete vs. incomplete percutaneous coronary intervention (PCI) for patients with chronic total occlusion (CTO) and multi-vessel disease (MVD). The study aimed to compare their clinical outcomes. METHODS: A total of 558 patients with CTO and MVD were divided into the optimal medical treatment (OMT) group ( n = 86), incomplete PCI group ( n = 327), and complete PCI group ( n = 145). Propensity score matching (PSM) was performed between the complete and incomplete PCI groups as sensitivity analysis. The primary outcome was defined as the occurrence of major adverse cardiovascular events (MACEs), and unstable angina was defined as the secondary outcome. RESULTS: At a median follow-up of 21 months, there were statistical differences among the OMT, incomplete PCI, and complete PCI groups in the rates of MACEs (43.0% [37/86] vs. 30.6% [100/327] vs. 20.0% [29/145], respectively, P = 0.016) and unstable angina (24.4% [21/86] vs. 19.3% [63/327] vs. 10.3% [15/145], respectively, P = 0.010). Complete PCI was associated with lower MACE compared with OMT (adjusted hazard ratio [HR] = 2.00; 95% confidence interval [CI] = 1.23-3.27; P = 0.005) or incomplete PCI (adjusted HR = 1.58; 95% CI = 1.04-2.39; P = 0.031). Sensitivity analysis of PSM showed similar results to the above on the rates of MACEs between complete PCI and incomplete PCI groups (20.5% [25/122] vs. 32.6% [62/190], respectively; adjusted HR = 0.55; 95% CI = 0.32-0.96; P = 0.035) and unstable angina (10.7% [13/122] vs. 20.5% [39/190], respectively; adjusted HR = 0.48; 95% CI = 0.24-0.99; P = 0.046). CONCLUSIONS: For treatment of CTO and MVD, complete PCI reduced the long-term risk of MACEs and unstable angina, as compared with incomplete PCI and OMT. Complete PCI in both CTO and non-CTO lesions can potentially improve the prognosis of patients with CTO and MVD.

Efficacy and safety of Runzao Zhiyang capsule for chronic urticaria: a systematic review and meta-analysis of randomized controlled trials.

Background: Chronic urticaria (CU) is a commonly seen skin disorder featured by recurring wheals, with or without angioedema, lasting for at least 6 weeks. Runzao Zhiyang capsule (RZC) has been widely applied to treat patients with CU. This study is aimed at systematically evaluating the efficacy and safety of RZC in treating CU. Materials and Methods: Randomized controlled trials (RCTs) of RZC on treating CU from Chinese and English databases were searched. Data were collected by two independent researchers. The Cochrane Collaboration tool was adopted for evaluating the risk of bias. The meta-analysis was performed with Review Manager 5.3 software. Sensitivity analysis and publication bias assessment were conducted by Stata 14.0 software. Results: Totally 27 studies were included in the analysis, involving 2,703 patients. The pooled results showed that compared with second-generation H1-antihistamines (sgAHs) therapy alone, RZC combined with sgAHs is more effective in improving the total effective rate (RR = 1.32, 95% CI: 1.25 to 1.39, p < 0.00001), the quality of life measured by Dermatology Life Quality Index (DLQI) (MD = -2.63, 95% CI: -3.68 to -1.58, p < 0.00001) and the serum IFN-γ level (SMD = 3.10, 95% CI: 1.58 to 4.62, p < 0.0001), and reducing the recurrence rate (RR = 0.39, 95% CI: 0.27 to 0.55, p < 0.00001), the serum total IgE level (SMD = -2.44, 95% CI: -3.51 to -1.38, p < 0.00001), the serum IL-4 level (SMD = -2.96, 95% CI: -4.10 to -1.83, p < 0.00001), and the incidence of adverse events including dizziness, fatigue, dry mouth, and constipation (RR = 0.53, 95% CI: 0.33 to 0.85, p = 0.009; RR = 0.46, 95% CI: 0.26 to 0.84, p = 0.01; RR = 0.57, 95% CI: 0.34 to 0.95, p = 0.03; RR = 0.24, 95% CI: 0.07 to 0.85, p = 0.03). Conclusion: The current evidence indicates that RZC may be an efficient therapeutic regimen in patients with CU. Nevertheless, owing to the suboptimal quality of the included studies, more large-scale, well-designed RCTs are required to verify the obtained findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier: CRD42022313177.

Prognostic value of nicotinamide N-methyltransferase in human cancers: Evidence from a meta-analysis and database validation.

BACKGROUND: Previous studies indicated that dysregulated expression of nicotinamide N-methyltransferase (NNMT) contributed to the tumor progression and predicted poor prognosis in various cancers. However, there was no exact conclusion on account of the contradictory results across studies. METHODS: The relevant studies up to December 7, 2020 were searched in PubMed, Web of Science, and Embase. The association between NNMT expression and prognostic outcomes was explored, including overall survival (OS), disease-free survival (DFS), and clinicopathological features. The bioinformatics database was used to validate the findings. RESULTS: Thirteen retrospective studies containing 2,591 patients with cancers were included in this analysis. High NNMT expression was significantly associated with shorter OS (hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.42-2.86, and P < 0.01) and DFS (HR = 1.59, 95% CI = 1.23-2.05, and P < 0.01) compared to low NNMT expression in cancers. Compared to patients with low NNMT expression, patients with high NNMT expression tended to have worse tumor differentiation (P = 0.03), earlier lymph node metastasis (P = 0.01), earlier distant metastasis (P = 0.02), and more advanced clinical stage (P < 0.01). CONCLUSION: High NNMT expression is an unfavorable factor of various cancers. NNMT is a promising indicator to predict the prognosis of various cancers and can serve as a potential therapeutic target in various cancers.

Specific gene module pair-based target identification and drug discovery.

Identification of the biological targets of a compound is of paramount importance for the exploration of the mechanism of action of drugs and for the development of novel drugs. A concept of the Connectivity Map (CMap) was previously proposed to connect genes, drugs, and disease states based on the common gene-expression signatures. For a new query compound, the CMap-based method can infer its potential targets by searching similar drugs with known targets (reference drugs) and measuring the similarities into their specific transcriptional responses between the query compound and those reference drugs. However, the available methods are often inefficient due to the requirement of the reference drugs as a medium to link the query agent and targets. Here, we developed a general procedure to extract target-induced consensus gene modules from the transcriptional profiles induced by the treatment of perturbagens of a target. A specific transcriptional gene module pair (GMP) was automatically identified for each target and could be used as a direct target signature. Based on the GMPs, we built the target network and identified some target gene clusters with similar biological mechanisms. Moreover, a gene module pair-based target identification (GMPTI) approach was proposed to predict novel compound-target interactions. Using this method, we have discovered novel inhibitors for three PI3K pathway proteins PI3Kα/ß/δ, including PU-H71, alvespimycin, reversine, astemizole, raloxifene HCl, and tamoxifen.