To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Objective To observe the effect of Bushen Huoxue Decoction(BSHX)on PI3K/Akt/mTOR signaling pathway and explore its possible mechanism in improving synaptic plasticity in a vascular dementia(VD)rat model.Methods Sprague-Dawley rats were randomly divided into sham operation group(Sham group),model group(VD group),Bushenhuoxue decoction group(BSHXD group),nimodipine group(NMDP group),with 10 rats in each group.The VD model of rats was established by two-vessel(2-VO)occlusion method.Rats in BSHXD group were given BSHXD at a weight of 10.14 g·kg-1,while rats in the NMDP group were given nimodipine decoction at 11 mg·kg-1.The SHAM group and the VD group were given saline at a weight of 10 mL·kg-1 once a day for 4 weeks.Morris water maze was used to observe the spatial learning and memory ability of rats in each group.Nissl staining was used to observe the damage of Nissl bodies and neurons in CA1 area of hippocampus of rats.The expression of synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)in hippocampal CA1 region was detected by immunohistochemistry.Golgi-Cox staining method was used to observe the number changes of dendritic branches and spines of hippocampal neurons.Transmission electron microscopy(TEM)observed the ultrastructural change of synapses.The protein and mRNA expressions of phosphatidylinositol 3-kinase(PI3K),serine-threonine kinase(AKT)and mammalian target of rapamycin(mTOR)in rat hippocampus were detected by Western blot and Reverse transcription quantitative PCR(RT-qPCR).Results Compared with the control group,the learning and memory ability of VD rats decreased.These rats showed abnormal synaptic ultrastructure of hippocampal neurons and neuronal cell damage,and this was accompanied by a decrease in the density of dendrite branches and dendritic spines of neurons.The expression of both SYN and PSD-95 proteins in the hippocampus decreased(P<0.05),and synaptic plasticity was damaged.Both mRNA and protein expression of PI3K,Akt,and mTOR in the hippocampus decreased in the VD rats(P<0.05).Also observed in VD rats was that administration of BHSX mitigated the learning and memory impairment observed in these animals,improved the morphology and synaptic ultrastructure of hippocampal neurons,increased the mRNA and protein expression levels of PI3K,Akt,mTOR,and increased the protein levels of SYN and PSD-95(P<0.05).Conclusion BSHX can alleviate the learning and memory impairment of VD rats and increase the protein expression levels of synapse-related proteins.These effects may be related to the promotion of synaptic plasticity by BSHX through activation of PI3K/Akt/mTOR signaling.

Objective To evaluate the ability of the ratio of peripheral blood white blood cell(WBC)counts to platelet counts to predict the onset of radiation-induced thymic lymphoma(TL)in a mouse model.Methods Mice were subjected to fractionated total-body irradiation(TBI)to established a TL model before the changes of the WBC-to-platelet ratio during the development and progression of TL were investigated.Four-week-old male C57BL/6J mice were randomized into the normal(non-irradiation)group and radiation exposure group that was subjected to 1.8 Gy TBI once weekly for four consecutive weeks.The survival and TL-incidence of those two groups were compared within 370 days of TBI.Histomorphology and hematoxylin & eosin(H&E)staining of the thymus were used for definite diagnosis of TL while flow cytometry was adopted to detect the frequency changes of T cells in the thymus,bone marrow and spleen.Peripheral blood(PB)cell counts were measured to analyze the changes of peripheral hemogram during TL pathogenesis.Results No mice in the normal group were diagnosed with TL while 83％of the irradiated mic suffered from TL within 370 days of fractionated TBI(P＜0.0001).Using histopathologic technology,medium-sized tumor cells were observed in the thymus of irradiated mice diagnosed with TL.Cytometric analysis showed decreased frequencies of CD4 mono-positive cells and increased frequencies of CD8 mono-positive cells in the thymus,bone marrow and spleen of mice diagnosed with TL.PB analysis displayed a significant increase in the WBC-to-platelet ratio one week prior to the TL-caused death in the irradiated mice(P＜0.01).Conclusion Elevation of the peripheral blood WBC-to-platelet ratio can help predict the onset of IR-induced TL of mice.

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Objective To investigate the effect of very-long-chain saturated fatty acids on Tau protein phosphorylation and membrane fluidity in human neuroblastoma SH-SY5Y cells,and to explore its role in the pathogenesis of Alzheimer's disease(AD).Methods Human neuroblastoma SH-SY5Y cells in logarithmic growth phase were randomly divided into control group,C22∶0 group,and C24:0 group.Cells in the control group were routinely cultured,while cells in the C22:0 and C24:0 groups were treated with culture medium containing 10 μmol·L-1very-long-chain saturated fatty acids C22:0 and C24:0,respectively.After 24 hours of incubation,cells were collected.The expression levels of total Tau protein,phosphorylated Tau protein at serine 396 site(p-Tau-ser396),glycogen synthase kinase 3β(GSK-3β),and phosphorylated GSK-3 β protein at serine 9 site(p-GSK-3β-Ser9)in cells of each group were detected by using Western blot.The malondialdehyde(MDA)level in cells of each group was determined by using the thiobarbituric acid method.The fluorescence recovery rate and diffusion coefficient of cell membranes were measured by using fluorescence recovery after photobleaching technique,and the fluidity of cell membranes was evaluated.Results The total Tau protein level in SH-SY5Y cells showed no statistically significant difference among the three groups(F=1.807,P＞0.05).However,there was a statistically significant difference in the level of p-Tau-ser396 in SH-SY5Y cells among the three groups(F=18.397,P＜0.05).Specifically,the level of p-Tau-ser396 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly higher than that in the control group(P＜0.05),and the level of p-Tau-ser396 in SH-SY5Y cells in the C24:0 group was significantly higher than that in the C22:0 group(P＜0.05).There was no statistically significant difference in the GSK-3 β protein level in SH-SY5Y cells among the three groups(F=0.351,P＞0.05).However,there was a statistically significant difference in the level of p-GSK-3β-Ser9 in SH-SY5Y cells among the three groups(F=13.330,P＜0.05).Specifically,the level of p-GSK-3β-ser9 in SH-SY5Y cells in the C22:0 and C24:0 groups was significantly lower than that in the control group(P＜0.05),and there was no statistically significant difference in the level of p-GSK-3β-ser9 in SH-SY5Y cells between the C22:0 group and C24:0 group(P＞0.05).The MDA level in SH-SY5Y cells in the C24:0 group was significantly higher than that in the control group and C22:0 group(P＜0.05);there was no statistically significant difference in the MDA level in SH-SY5Y cells between the control group and C22:0 group(P＞0.05).The fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells in the C22:0 and C24:0 groups showed a decreasing trend compared to the control group,but there was no statistically significant difference in the fluorescence recovery rate and diffusion coefficient of SH-SY5Y cells among the three groups(F=3.891,3.649,P＞0.05).Conclusion Very-long-chain saturated fatty acids C22:0 and C24:0 can promote hyperphosphorylation of Tau protein,induce cellular oxidative damage,and tend to reduce the fluidity cell membranes.Very-long-chain saturated fatty acids may be one of the factors that cause the onset of AD.

Waardenburg syndrome is a rare genetic disease of auditory pigmentation. The main symptom is sensorineural hearing loss. Pigment disorders and other developmental defects in skin, hair, iris, fundus and other parts are specifically divided into four different subtypes, each of which corresponds to different pathogenic genes, which encode transcription factors and signaling molecules that play a key role in the development process of neural crest cells into melanocytes. Because there are multiple subtypes of Waardenburg syndrome, different subtypes exhibit different symptoms, signs and ocular manifestations. Patients with Waardenburg syndrome are often first treated in ENT head and neck surgery due to hearing loss. Lack of theoretical knowledge related to Waardenburg syndrome by ophthalmologists may lead to misdiagnosis or missed diagnosis. Although there are currently limited treatments for the disease, with the continuous development of gene therapy and hearing management methods, the future treatment prospects will be broader.

Primary hepatic carcinoma, hepatic carcinoma for short, is a common gastrointestinal tumor with an insidious onset and rapid progression, and its incidence rate is increasing year by year, seriously threatening the life and health of our people. At present, there is still a lack of specific markers for early diagnosis and treatment of hepatic carcinoma, so the research on its biological characteristics and pathogenesis has become very urgent. Metabolic reprogramming is one of the main characteristics of tumor cells, and lipid metabolic reprogramming is involved in the occurrence and development of hepatic carcinoma. Therefore, the key metabolic enzymes and regulatory molecules in the process of lipid metabolism are considered as important targets for the diagnosis and treatment of hepatic carcinoma. This paper mainly focuses on the signaling pathways and regulatory molecules related to hepatocellular carcinoma lipid metabolism, as well as the related anti-hepatoma drugs, so as to provide new ideas for the prevention and treatment of hepatic carcinoma.

Objective:To solve the problems in intensity-modulated radiation therapy (IMRT) planning, such as large labor cost and high dependence on the experience of physicists and great inconsistency in the quality of plan, and to discuss an unsupervised automatic treatment planning procedure of IMRT.Methods:The eclipse scripting application programming interface (ESAPI) within the Eclipse treatment planning system (TPS) 15.6 and optimization parameters tree search algorithm (OPTSA) were used to emulate and realize the whole planning process. Interacted with the TPS through ESAPI, relevant dosimetric parameters were input and output. The OPTSA evaluated the plan qualities based on dosimetric parameters of the targets and organs at risk (OARs) and iteratively adjusted the optimization objective parameters to achieve a progressively improving IMRT plan. In order to verify the effectiveness of the automatic planning, twenty historical rectum cancer cases were selected from the clinical database, and the dose distribution and specific dosimetric parameters were compared between the plans generated by the OPTSA and the manual plans under the same constraints.Results:All the auto plans have met clinical requirements. Furthermore, 90% and 10% of the auto plans were deemed as clinically improved and equally compared with the manual plans, respectively. The average CI for the PTV was 0.88 and 0.80 for the auto and manual plans respectively. Compared with the manual plans, the mean doses of all the OARs in the auto plans were reduced by 11% in average. The average elapsed time of automatic planning and manual planning was (28.15±3.61) and (36.7±4.6) min, respectively.Conclusions:The plans created by the proposed algorithm have been shown to be at least as good as the manual plans. In addition, this method can shorten the labor time in plan designing while ensuring the plan quality and consistency of the plan.

Objective:To investigate the performance of W2 plastic scintillator in megavolt photon and electron beams.Methods:The photon and electron beam energy provided by linear accelerator was used to collect data of the W2 scintillator. The parameters include the electrometer reading stability, W2 dose and dose rate linearity, and angular response. And the dose uncertainty of the W2 correction factors was also investigated.Results:The standard deviation of the electrometer reading stability was between 0.03 and 0.47. The linear regression factors of W2 dose were all 1.0; the maximum deviation of the dose rates was 0.61%. The Cerenkov light radiation correction factor(CLR) for 6 and 10 MV were 0.741 and 0.746, respectively, and the CLR for 6, 9, 12 and 15 MeV were 0.750, 0.753, 0.757 and 0.757, respectively. The maximum deviation of dose uncertainty for 15 MeV was 3.15%.Conclusions:The signal obtained by the blue and green channel was no angular dependence, the same as the high-energy electron beam, which verified that the Cerenkov radiation correction factor has good linearity. W2 plastic scintillator can be applied to non-coplanar radiotherapy dosimetry.