To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

OBJECTIVE: To study effective methods for reducing lung V₅, V₁₀, and mean lung dose (MLD) in the design of volumetric modulated arc therapy for central lung cancer by using different arc configurations and dose-limiting blocks designs. METHODS: Five groups of plans were designed for the enrolled patients. Group A used a full-arc field. Group B used a partial-arc field. Groups C, D, and E used full-arc fields with vertical-length, semi-ring, and triangular dose-limiting blocks added respectively. The dosimetric similarities of target areas and the dosimetric differences in lung V₅, V₁₀, V₂₀, and MLD among the groups were compared. RESULTS: Compared with group A, groups B, C, D, and E had decreased homogeneity and conformity of the target area, but significantly lower V₅ and V₁₀ of the whole lung. The MLD of groups C, D, and E was lower than that of group A. CONCLUSION Using a full-arc field combined with dose-limiting blocks can effectively reduce lung V₅, V₁₀, MLD, and monitor units (MU).
Lung Neoplasms/radiotherapy* ; Humans ; Radiotherapy, Intensity-Modulated/methods* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Lung/radiation effects*

ObjectiveTo explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.MethodWe used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin (55 mg/kg), geniposide (5 mg/kg), or their 11:1 combination. Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining, Evans blue assay, enzyme-linked immunosorbent assay, and Western blot.ResultsThe results revealed that the nuclear factor-kappa B (NF-κB) signaling pathway is inhibited in combination treatment of cerebral ischemia. Ten targets were identified as key nodes in the protein–protein interaction network: interleukin 6 (IL-6), interleukin-1β, interleukin 18, C–C motif ligand 2, C–C motif ligand 4, interleukin 10, interferon-γ-inducible protein 10, C–C motif ligand 3, tumor necrosis factor-α (TNF-α), interleukin-1α. The baicalin-geniposide combination significantly reduced infarct volume, improved neurological deficits, and alleviated brain edema/blood–brain barrier leakage compared with monotherapy. Additionally, it significantly inhibited toll-like receptor 4 (TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-α and IL-6 levels.ConclusionThe baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.

Objective:To explore the radiological damage to cells induced by the delayed particles of 9C-ions for heavy ion therapy, as well as the microdosimetric distribution and biological effects of these particles on a single model of V79 Chinese hamster lung cells. Methods:The Monte Carlo program was employed to simulate the endonuclear absorbed doses of α particles with various energies (3-10 MeV) transported in cells (cell radius RC = 10 μm, nucleus radius RN = 5 μm). Then, the result were compared with the S values ( SN←N, SN←Cy, and SN←CS) derived using the medical internal radiation dose (MIRD) method to demonstrate the feasibility of Monte Carlo simulations. Finally, the energy deposition of the delayed particles of 9C-ions generated at three sites (i.e., on the surface and in the cytoplasm and nucleus of the V79 cell model) during their transport in targets was simulated, and the result ing cell surviving fraction was analyzed. Results:Monte Carlo and MIRD method yielded differences in S values of 1.91%-4.95% for SN←N (nucleus to nucleus), 1.48%-5.11% for SN←Cy (cytoplasm to nucleus), and -1.99% to 0.80% for SN←CS(surface to nucleus), indicating highly consistent S values derived using both method(differences < 6%). When a 9C-ion decayed on the surface of the V79 cell model and the produced secondary particles entered the cell, the average endonuclear absorbed dose was 10 -2 Gy orders of magnitude, with a cell surviving fraction of about 88%. In the case where decay occurred in the cytoplasm, the cell surviving fraction was about 80%. However, when the 9C ion decayed in the nucleus, α particles had short ranges and deposited most of their energy in the cell (mean endonuclear absorbed dose: 0.1 Gy). In this case, severe cell damage was induced, with the cell surviving fraction reducing to about 53%. Conclusions:9C-ions emit secondary charged particles due to decay, among which α particles cause great damage to cells when entering the nucleus and trigger evident biological effects.

The theory of "yang transforming qi and yin shaping up body" comes from Huangdi Neijing (Inner Canon of Yellow Emperor),which describes the basic form of human metabolism dominated by "yang transforming qi":the effect of " yang transforming qi" leads the energy metabolism of human body,while the effect of "yin shaping up body" leads the material metabolism. Metabolic syndrome is a clinical syndrome with metabolic disorders of protein,fat and carbohydrate. The theory of "yang transforming qi and yin shaping up body" has a strong guiding value for the pathogenesis analysis and clinical differentiation and treatment of metabolic syndrome. Yin and yang represent the two basic trends of the change and development of things,and the functions of "transforming qi" and "shaping up body" are the main manifestations of them in metabolism. From this perspective,this paper suggests that the key pathogenesis of metabolic syndrome should be "insufficiency of yang transforming qi and impairment of yin shaping up body" based on the mutual assistance of yin and yang. On this basis we take "coordinating yin-yang and promoting the reproduction of them" as the main directions of therapy,which provides a new idea for the treatment of metabolic syndrome.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To study the effects of gantry acceleration limitations of a linear accelerator (linac) on the dosimetry of volumetric modulated arc therapy (VMAT) plans, machine efficiency, and dose verification result of VMAT plans and to explore the optimal selection of gantry motion models in the Pinnacle treatment planning system.Methods:Ten cases of nasopharyngeal carcinoma, non-small cell lung cancer, sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, and invasive ductal carcinoma of the breast were each selected for this study. Then two models were set up in the Pinnacle v9.10 treatment planning system, namely the one allowing gantry acceleration and the one limiting gantry acceleration. The same field arrangement, optimized target parameters, and optimized weights of VMAT plans were adopted in the two models, in order to analyze the dosimetric variations in targets and organs at risk (OARs) and compare the differences in treatment time and gamma passing rates.Results:The treatment time of the enrolled patients under the model allowing gantry acceleration was significantly lower than that of the patients under the model limiting gantry acceleration was adopted ( t=-6.751, -0.209, -19.523, -28.999; P< 0.05) and decreased by 15.27%, 18.07%, 19.71%, and 28.75%, respectively. Meanwhile, the conformity and uniformity of target areas were affected, while there was no statistical significance in the gamma passing rates in the validation of VMAT plans ( P>0.05). For the cases of nasopharyngeal carcinoma (NPC), the maximum dose to brainstem PRV increased by 1.25%. For the cases of lung cancer, the maximum dose to the spinal cord and lung V20 increased by 1.19% and 1.21%, respectively, while lung V5 decreased by 1.21%. For the cases of sigmoid adenocarcinoma with retroperitoneal lymph node metastasis, the mean doses to bilateral kidneys, livers, small intestine, and colon all increased. For the cases of breast cancer, lung V10 on the opposite side of cancer increased by 1.66% and the mean dose to the lungs on the same side of cancer decreased by 7.45%. Conclusions:The model allowing gantry acceleration allows the treatment time to be significantly shortened and the treatment efficiency improved. Although this model had the shortcomings such as affecting the conformity and uniformity of target areas to a certain extent and increasing the doses to some OARs, clinical requirements for dosimetry were still met. Therefore, it is recommended to use the model allowing gantry acceleration in the Pinnacle planning system.

Ion channels are crucial in the generation and modulation of excitability in the nervous system.Recent studies have demonstrated that 977 genes are associated with epilepsy,among which more than 60 genes encode ion channels predominantly,mainly including voltage-gated channel genes:sodium channel (SCALA,SCN1B,SCN2A),potassium channel (KCNA2,KCNC1,KCNT1,KCNQ2,KCNQ3),chloride channel (CLCN2),calcium channel (CACNA1H,CACNA1A),and ligand-gated ion channel genes,which include GABA receptor genes (GABRA1,GABRB3,GABRD and GABRG2),neuronal nicotinic receptor genes (CHRNA4,CHRNB2) and other genes (HCN1,LGI1 and PRRT2).This review mainly focuses on the advances in ion channel genes and genetics of epilepsy,in order to assist the diagnoses and treatment in clinic.

Objective To investigate the effect of low salt diet on vascular remodeling of rat induced by high fructose(HF).Methods Wistar male rats weighed 180-200 g were fed for 8 weeks and randomly divided into 6 groups:(1) control group was given the normal fodder and distilled water;(2) high fructose group(HF) was given normal fodder (0.5 ％ NaCl,w/w) and fructose water(10 ％,w/v);(3) high-salt group (HNa) was given high salt fodder (7 ％ NaCl,w/w) and distilled water;(4) high fructose combined with high salt diet group(HFNa) was simultaneously given high salt fodder and 10 ％ fructose water;(5)high fructose combined low salt group(HFLNa) was simultaneously given low salt fodder and 10％ fructose water;(6) high fructose combined with spirotaclone group(HFE) was given 10％ fructose water for 4 weeks and then added with spirotaelone(50 mg · kg-1 · d-1 by tube feeding) for continuous 4 weeks.The changes of arterial blood pressure,vascular wall histological evaluation and expression of α-SMA and fibronectin in vascular wall were detected in each group.Results (1) Compared with the blood pressure[(111.03 ±9.17) mm Hg] in the control group,the blood pressure in the HF and HNa groups were (133.94± 5.86) mm Hg and (128.09±7.56) mm Hg respectively,which were significantly increased(P＜0.05);(2) HF mainly caused the hyperplasia of vascular wall middle layer smooth muscle.The a-SMA expression results in the HF group was (0.006 3 ±0.000 21),which in the control group was (0.004 6 ± 0.000 31),the difference was statistically significant(P＜0.05),moreover which promoted the elastic fibers increase;while HNa mainly stimulated the elastic fibers to thicken and extracellular matrix deposition,the fibronectin expression was 0.002 6 ± 0.000 2 in the HNa group and (0.004 7±0.000 2)in the HF group,compared with(0.001 3±0.000 1)in the normal group,which were significantly increased(P＜0.001);(3) the blood pressure was (106.04±9.59) mm Hg in the HFLNa group,(103.99±7.12) mm Hg in the HFE group,compared with(133.94±5.86) mm Hg in the HF group,showing that the blood pressure in the HFLNa group and HFE group was significantly decreased compared with the HF group (P＜0.05);moreover the vascular remodeling in the HFLNa group(0.006 8±0.000 2) and HFE group (0.004 2±0.000 4) was improved,and compared with the HF group(0.006 3±0.000 2),α-SMA expression was significantly decreased (P＜0.05).Conclusion Low salt diet can effectively improve vascular remodeling induced by HEF.

Objective: To explore the short and mid-term efficacy of device closure of patent foramen ovale (PFO) for treating the patients with PFO combining cryptogenic stroke (CS) and transient ischemic attack (TIA). Methods: A total of 56 PFO patients with CS and TIA receiving device closure in our hospital from 2009-05 to 2015-12 were retrospectively studied. Transthoracic echocardiography (TTE), electrocardiogram (ECG), chest X-ray were examined at 24h, 1 month, 3 and 6 months after theoperation; telephone visit was conducted every 6 months thereafter. Results: There were 54/56 PFO patients combining CS and 2 combining TIA; 53 (94.6%)patients received PFO occluder from Starway medical technology. Aspirin was used for 6 months after the operation. The patients were followed-up for the average of (34.67±23.24) months. No body suffered from post-operative stroke and TIA; no residual shunt was observed. Conclusion: The short and mid-term efficacy of device closure has been satisfactory for treating the patients with PFO combining CS and TIA; its overall clinical value should be further investigated in large population and long-term study.