In order to further promote the standardization of the integrated traditional Chinese and western medicine treatment of atopic dermatitis(AD),the team of Professor Chen Dacan,who is honored as the Qihuang Scholar,developed the Clinical Practice Guidelines for Integrated Traditional Chinese and Western Medicine in Atopic Dermatitis(hereinafter referred to as Guidelines for AD).This paper detailed the process of development of Guidelines for AD,and analyzed the characteristics of Guidelines for AD,as well as the difficulties and countermeasures encountered during such a time.The development of Guidelines for AD follows the methodology of international guidelines for clinical trial.Experts specializing in various disciplines,such as traditional Chinese medicine,western medicine,integrated traditional Chinese and western medicine,and methodology,composed an expert group and a working group.On the basis of systematic literature research,the clinic experiences of frontline experts were well-summarized,and the draft of Guidelines for AD was formed after several meetings and discussions.In the process of developing Guidelines for AD,quite a number of problems were encountered,and the project team found the corresponding countermeasures after analyzing these problems.The countermeasures became the characteristics of Guidelines for AD:the integration of traditional Chinese medicine therapies and western medicine therapies,and the evaluation of the evidence of integrated traditional Chinese and western medicine solved the problem of traditional Chinese and western medicine diagnosis and treatment of AD lacking standardization;the adequately combination of the evidence with the experience of clinical practice solved the problems of the low overall level and the insufficiency of traditional Chinese medicine evidence for AD;the establishment of management goals and strategies for AD after taking the advantages of both traditional Chinese medicine and western medicine into account was in line with the international treatment and management concepts;the formulation of individualized traditional Chinese and western medicine therapy based on the integration of traditional Chinese medicine therapy and western medicine therapy met the clinical needs of patients with different characteristics of AD.The development process of Guidelines for AD and the analysis of problems and countermeasures during such a time will provide reference and reflection for the subsequent establishment of clinical guidelines for the integrated traditional Chinese and western medicine in other diseases.

To identify factors associated with the recurrence of polymyalgia rheumatica(PMR) within one year.

Toxoplasma gondii is an obligatory intracellular parasite which infects a variety of warm-blooded animals and causes toxoplasmosis. Toxoplasmosis seriously endangers human health and animal husbandry production. As one of the effective gene editing tools, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been widely used for knockout of genes in T. gondii. This review summarizes the applications of the CRISPR/Cas9 technology in vaccines against single- and double-gene deletion strains of T. gondii, so as to provide insights into development of toxoplasmosis vaccines.

Objective:To investigate the alterations of multilayer network and dynamic causal connectivity in patients with bilateral sudden sensorineural hearing loss.Methods:The hearing ability, neural-scale data and resting-state functional magnetic resonance imaging(fMRI)data of 60 patients with bilateral sudden sensorineural hearing loss from the Department of Otolaryngology and 60 healthy controls from Physical Examination Center, Nanjing First Hospital were collected from January 2022 to January 2024. Multilayer brain network analysis was computed to identify the nodes with abnormal switching rate. Then these abnormal nodes were used as regions of interest (ROIs) in the subsequent dynamic causal model analysis. The SPSS 26.0 software was used to analyze causal connectivity between two groups based on independent-sample Mann-Whitney U test. And Pearson correlation coefficients between fMRI results and clinical parameters were calculated. Results:Pure tone audiometry test showed that the left and right hearing thresholds of bilateral sudden sensorineural hearing loss were significantly higher than those of healthy controls( Z=-9.460, -9.462, both P<0.01). The score of depressive emotion in patients with bilateral sudden hearing loss was 6.00(2.00, 9.00).Multilayer brain network analysis showed that the switching rates in the left superior frontal gyrus (0.073(0.049, 0.102), Z=3.603, P<0.001), left anterior cingulate gyrus (0.077(0.044, 0.105), Z=3.189, P=0.001), right hippocampus (0.080(0.045, 0.116), Z=3.616, P<0.001), left para-hippocampal gyrus (0.080(0.043, 0.108), Z=3.577, P<0.001), left superior parietal gyrus (0.079(0.047, 0.103), Z=3.160, P=0.002), and right inferior parietal gyrus (0.078(0.043, 0.105), Z=3.396, P<0.001) in patients with bilateral sudden sensorineural hearing loss were lower that those in healthy controls. These six brain areas were used as ROIs to compute dynamic causal model analysis, and the results showed that the connection strength from left superior frontal gyrus to the left para-hippocampal gyrus in patients with bilateral sudden sensorineural hearing loss was significantly higher than that in healthy controls ( Z=-2.593, P<0.05). Additionally, enhanced connectivity from left superior frontal gyrus to the left para-hippocampal gyrus was positively correlated with duration of hearing loss ( r=0.376, P=0.003). Conclusions:Bilateral sudden sensorineural hearing loss patients have decreased switching rates in many brain areas, and the causal connectivity from left superior frontal gyrus to the left para-hippocampal gyrus is enhanced.

Objective:To further investigate the safety and efficacy of Belimumab in the treatment of patients with systemic lupus erythematosus (SLE).Methods:All SLE patients treated with Belimumab from May 1, 2020 to February 1, 2022 in Peking Union Medical College Hospital were retrospectively collected and analyzed. The clinical manifestations, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score, and laboratory test such as levels of anti-dsDNA antibody, the medication before and after Belimumab treatment, adverse events were collected. Normally distributed data were tested using the t-test, otherwise the Wilcoxon paired signed rank test was used. Results:A total of 81 patients were enrolled in this study. The use of belimumab could significantly decrease the SLEDAI-2000 score [10.00(7.75, 12.00) vs. 4.00(3.75, 6.00), Z=-5.38, P<0.001], ESR of SLE patients [19.50(12.75, 32.25) mm/1 h vs. 14.00(7.75, 20.25) mm/1 h, Z=-3.71, P=0.003], anti-dsDNA titer detected by CLIFT [300.00 (117.00, 864.00) vs. 183.00(100.00, 471.00), Z=-4.15, P=0.001], meanwhile, increase the complement C3 [0.78 (0.62, 0.97)g/L vs. 0.69 (0.55, 0.84)g/L, Z=-4.68, P<0.001], and the complement C4 [0.12 (0.08, 0.19)g/L vs. 0.10 (0.05, 0.14)g/L, Z=-4.78, P<0.001]. We also observed that with the use of Belimumab, the dosage of Glucocorticoids decreased significantly, which were [10.00(7.50, 22.50) mg vs. 7.50(5.00, 10.00) mg, Z=-4.90, P<0.001]. In addition, the antibody of IgG, IgA and IgM decreased significantly. Only one patient stopped the administration of Belimumab due to the low level of immunoglobulin. Conclusion:Belimumab can alleviate disease activity of patients with SLE and help in safely tapering the daily dose of glucocorticoid with good safety.

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

Yeast autolysis affects the flavor and quality of beer. The regulation of yeast autolysis is a need for industrial beer production. Previous studies on brewer's yeast autolysis showed that the citric acid cycle-related genes had a great influence on yeast autolysis. To explore the contribution of isocitrate dehydrogenase genes in autolysis, the IDP1 and IDP2 genes were destroyed or overexpressed in typical lager yeast Pilsner. The destruction of IDP1 gene improved the anti-autolytic ability of yeast, and the anti-autolytic index after 96 h autolysis was 8.40, 1.5 times higher than that of the original strain. The destruction of IDP1 gene increased the supply of nicotinamide adenine dinucleotide phosphate (NADPH) and the NADPH/NADP⁺ ratio was 1.94. After fermentation, intracellular ATP level was 1.8 times higher than that of the original strain, while reactive oxygen species (ROS) was reduced by 10%. The destruction of IDP2 gene resulted in rapid autolysis and a decrease in the supply of NADPH. Anti-autolytic index after 96 h autolysis was 4.03 and the NADPH/NADP⁺ ratio was 0.89. After fermentation, intracellular ATP level was reduced by 8% compared with original strain, ROS was 1.3 times higher than that of the original strain. The results may help understand the regulation mechanism of citric acid cycle-related genes on yeast autolysis and provide a basis for the selection of excellent yeast with controllable anti-autolytic performance.
Humans ; Isocitrate Dehydrogenase/genetics* ; NADP ; Reactive Oxygen Species ; Autolysis ; Adenosine Triphosphate

Mitophagy is a process whereby cells selectively remove mitochondria through the mechanism of autophagy, which plays an important role in maintaining cellular homeostasis. In order to explore the effect of mitophagy genes on the antioxidant activities of Saccharomyces cerevisiae, mutants with deletion or overexpression of mitophagy genes ATG8, ATG11 and ATG32 were constructed respectively. The results indicated that overexpression of ATG8 and ATG11 genes significantly reduced the intracellular reactive oxygen species (ROS) content upon H₂O₂ stress for 6 h, which were 61.23% and 46.35% of the initial state, respectively. Notable, overexpression of ATG8 and ATG11 genes significantly increased the mitochondrial membrane potential (MMP) and ATP content, which were helpful to improve the antioxidant activities of the strains. On the other hand, deletion of ATG8, ATG11 and ATG32 caused mitochondrial damage and significantly decreased cell vitality, and caused the imbalance of intracellular ROS. The intracellular ROS content significantly increased to 174.27%, 128.68%, 200.92% of the initial state, respectively, upon H₂O₂ stress for 6 h. The results showed that ATG8, ATG11 and ATG32 might be potential targets for regulating the antioxidant properties of yeast, providing a new clue for further research.
Mitophagy/genetics* ; Saccharomyces cerevisiae/genetics* ; Antioxidants ; Hydrogen Peroxide/pharmacology* ; Reactive Oxygen Species

The Gastroesophageal reflux disease(GERD)is related to the dynamic disorder of the digestive tract caused by the imbalance of the viscera and meridians.The spleen and stomach are the hub of the qi machinery,transforming the essence of water and valley into energy and regulating the Yin and Yang of all bodies.The sympathetic balance between Ren-Du and Qi is the motivity of the spleen and stomach.Interstitial cells of Cajal(ICC)are the hub of digestive motility,which can maintain mitochondrial energy metabolism through mitochondrial autophagy and improve the digestive motility.Therefore,in this paper,the molecular biological basis of GERD was discussed based on the"regulating pivot with pivot"theory that the pivots of viscera and meridians drive ICC mitochondrial energy balance.It also explains the feasibility of Qi-Shi-Sheng-Jiang-Gui-Yuan Decoction in treating GERD based on"regulating pivot with pivot",which is helpful to realize the microscopization and concretization of"regulating pivot with pivot"theory and realize the modernization of TCM theory.

Objective:To detect the levels of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in the serum of patients with early diabetic retinopathy (DR) and to explore their value in the treatment of DR.Methods:Fifty-nine patients with type 2 diabetes mellitus from March 2019 to June 2020 in the Yulin Second Hospital were collected and divided into the non-diabetic retinopathy (NDR) group (32 cases) and background stage diabetic retinopathy (BDR) group (27 cases) according to the DR grading criteria, and 29 healthy subjects were enrolled in the healthy control (HC) group. Serum VEGF levels were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA), and serum NO levels were measured by the nitrate reductase method (one-step method). Pearson analysis was used to correlate serum VEGF with NO levels in each group, and a logistic regression model was used to analyze the risk factors for DR.Results:Compared with the HC group, the differences in serum VEGF and NO levels of patients in the BDR group were statistically significant (all P < 0.05). The serum VEGF and NO levels were positively correlated in all groups (all P < 0.01). Duration of diabetes, smoking, glycated hemoglobin A1c (HbA1c), serum VEGF, and NO levels were high risk factors for DR. Conclusions:Serum VEGF and NO levels may be potential pathological mechanisms for the development of microvascular complications in patients with type 2 diabetes, and the interaction may induce or accelerate the progression of DR. This study is expected to provide a new idea of complementary or combined treatment in the treatment of DR.