Tripterygium wilfordii is widely used in the treatment of immune system disease and has a remarkable curative effect. Triptolide and Tripterygium glycosides are the most commonly used active ingredients in clinical practice， but their treatment window is narrow and there are many side effects. The damage involves the reproductive system， blood system， cardiovascular system， digestive system， etc. Based on clinical observations and literature summaries， the symptoms of adverse reactions mostly occur in the digestive system （liver and gastrointestinal tract）. Relevant scholars have launched a lot of studies of the manifestations of liver injury induced by T. wilfordii and the mechanism of liver injury. The mechanism is mainly related to liver cell apoptosis， induction of oxidative stress， immune injury， excessive autophagy of liver cells， abnormal fatty acid metabolism， and abnormal enzyme metabolism in liver tissues. This article reviewed and summarized relevant literature on gastrointestinal injury caused by T. wilfordii， but there are few studies on the manifestations and mechanisms of adverse reactions， which still need further research by scholars. In addition， this article also summarized the research on how to reduce toxicity and enhance efficacy of prescriptions prepared from T. wilfordii in the digestive system， mainly involving compatibility with western medicines （Methotrexate， Leflunomide， Iguratimod， etc.）， use along or combination with Chinese medicines （single Chinese medicine， Chinese medicine monomers， and Chinese medicine compounds）， acupuncture and moxibustion （electroacupuncture and moxibustion）， dosage form improvement （glycol plastid gel， self-dissolving microneedle， solid lipid nanoparticles， gastric floating sustained-release capsules， etc.）， processing （steaming， stir-frying， radish seed processing， money grass processing， licorice processing， etc.）， and other methods to reduce toxicity. To sum up， this article analyzed the manifestations， mechanisms， and methods of reducing toxicity and enhancing efficacy of T. wilfordii-induced liver injury and gastrointestinal injury by sorting out relevant literature， in order to provide a reference for the clinical application of T. wilfordii and some research ideas for the future in-depth study of T. wilfordii-induced digestive system injury.

ObjectiveTo observe the mechanism of chronic psychological stress aggravating idiopathic pulmonary fibrosis （IPF） in rats and the regulatory effect of Xiaoyaosan. MethodSixty SD rats were acclimatized for one week and then randomly divided into five groups： sham operation group， IPF group， IPF and depression model group， pirfenidone group， and pirfenidone + Xiaoyaosan group， with 12 rats in each group. The IPF group was induced by intratracheal instillation of bleomycin （5 mg·kg^-1） and administered 0.9% sodium chloride solution intragastrically. The model group was induced with bleomycin （5 mg·kg^-1） combined with chronic unpredictable mild stress to establish a rat model of IPF and depression and administered 0.9% sodium chloride solution intragastrically. Concurrently， the pirfenidone group was administered pirfenidone aqueous solution （50 mg·kg^-1） intragastrically， and the pirfenidone + Xiaoyaosan group was administered pirfenidone aqueous solution （50 mg·kg^-1） and Xiaoyaosan decoction （19.27 g·kg^-1） intragastrically. The experiment lasted for four weeks. Various parameters， including body weight， food intake， sucrose consumption rate， open field behavior， lung function， lung coefficient， pathological changes in lung tissue， and hydroxyproline （HYP） content were compared among the groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum cortisol （CORT）， corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） levels， and serotonin （5-HT） levels in serum and hippocampus. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in serum and lung tissue were also measured. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA expression of IL-1β， TNF-α， IL-6， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear transcription factor-κB p65 （NF-κB p65） in lung tissue. Western blot was used to detect the expression of proteins related to the p38 MAPK/NF-κB signaling pathway. ResultCompared with the normal group， IPF and depression model group showed slow weight gain， reduced food intake， decreased sucrose consumption rate， reduced total distance and average speed of movement in the open field test， weakened lung function， increased lung coefficient （P<0.01）， significant inflammatory cell infiltration in lung tissue by hematoxylin-eosin （HE） staining， collagen fiber deposition by Masson staining， and increased HYP content （P<0.01）. There were elevated levels of serum CORT， CRH， and ACTH （P<0.05， P<0.01）， increased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue， decreased 5-HT levels in serum and hippocampus， and increased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue （P<0.01）. Compared with the IPF and depression model group， the depression and IPF of rats in the pirfenidone + Xiaoyaosan group were effectively ameliorated， as evidenced by faster weight gain， increased food intake and sucrose consumption rate， increased total distance and average speed of movement in the open field test， enhanced lung function， reduced lung coefficient （P<0.01）， decreased inflammatory cell infiltration by HE staining， reduced collagen fiber deposition by Masson staining in lung tissue， and decreased HYP content （P<0.01）. Decreased serum CORT， CRH， and ACTH levels （P<0.05， P<0.01）， decreased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue （P<0.05， P<0.01）， increased 5-HT levels in serum and hippocampus （P<0.05， P<0.01）， and decreased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue were also noted （P<0.05， P<0.01）， with the effects of Xiaoyaosan + pirfenidone being more significant. ConclusionChronic unpredictable stress exacerbates the progression of IPF in rats. The combination of Xiaoyaosan and pirfenidone not only improves depressive-like behavior but also alleviates pulmonary fibrosis， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway and inhibition of excessive expression of inflammatory factors.

Objective To explore risk factors of early lung infection after liver transplantation and to construct a prediction model of early lung infection after liver transplantation.Methods The clinical data of 269 patients who underwent orthotopic liver transplantation for the first time were retrospectively analyzed.Patients were divided into the infected group(n=97)and the non-infected group(n=172)according to whether pulmonary infection occurred within 30 days after operation.The preoperative general data,preoperative laboratory examination results,intraoperative and postoperative data of the patients were collected.Multivariate Logistic regression analysis were used to screen risk factors of pulmonary infection.Based on the results of multivariate analysis,the prediction model was constructed and the prediction efficiency of the model was evaluated.Results Univariate and multivariate Logistic regression analysis showed that preoperative PNI≤41.70(OR=1.972,95%CI:1.047-3.714,P=0.036),LMR≤1.52(OR=2.020,95%CI:1.102-3.705,P=0.023),MELD score＞10.72(OR=1.985,95%CI:1.103-3.573,P=0.022),operative time＞448.00 min(OR=2.676,95%CI:1.515-4.727,P=0.001)and intensive care unit(ICU)hospitalization time＞4.0 days(OR=2.623,95%CI:1.335-5.154,P=0.005)were independent risk factors for early pulmonary infection after liver transplantation.The ROC area under the curve(AUC)of the prediction model based on the results of multivariate Logistic regression analysis was 0.768,the sensitivity was 80.41%and the specificity was 60.47%.Conclusion The prediction model based on PNI,LMR,MELD score,operation time and ICU hospitalization time can effectively predict the occurrence of early pulmonary infection after liver transplantation.

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Xiaoyaosan， a classical prescription for mental disorder recorded in Formulary of the Bureau of Taiping People's Welfare Pharmacy（《太平惠民合剂局方》）， is composed of Bupleuri Radix， Angelicae Sinensis Radix， Paeoniae Radix Alba， Atractylodis Macrocephalae Rhizoma， Poria， Zingiberis Rhizoma Praeparatum， Menthae Haplocalycis Herba， and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. Clinical practices and experiments have proved that it can be used for primary depression， anxiety， as well as the depression induced by various somatic disorders， such as gynecological diseases， internal diseases， and digestive system diseases， as evidenced the improvement of Hamilton depression rating scale score， self-rating depression scale score， etc. Xiaoyaosan has been verified to be remarkably effective， with high compliance and no obvious adverse reactions in patients. Xiaoyaosan mainly acts on monoamine neurotransmitters 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA）， adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in hypothalamic-pituitary-adrenal axis， pro-inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factored （TNF）-α， and orexin， ghrelin， and leptin in intestinal microecology and brain-gut axis， to regulate the neurobiochemical mechanism， endocrine mechanism， immune mechanism， and abnormal brain structure， thereby preventing and alleviating depression. However， the antidepressant mechanism of Xiaoyaosan needs to be further discussed. Through literature research， this paper analyzes the clinical application and basic mechanism of Xiaoyaosan in the treatment of depression， which is expected to serve as a reference for the application of this prescription in the clinical prevention and treatment of depression and improvement of the quality of life of patients， and further research on the antidepressant mechanism of Xiaoyaosan.

【Objective】 To explore the establishment methods of transgenic human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) based on the transposons, and attempt to apply it on the nude mice mode with glioma. 【Methods】 PiggyBac transposon system specially designed by us was used to prepare non-targeting and Her2-targeting hUC-MSCs that can stably express TRAIL through puromycin screening. The glioma cells expressing firefly luciferase (U87MG-LUC) were injected into the skull of the immunodeficient mice (BALB/c-nu/nu) with 1×10⁶ cells per mouse. After 7 days of injection, the mice transplanted with U87MG were detected with a small animal living imager to determine the size and location of the tumors in skull. Then we injected the glioma-transplantation nude mouse with two kinds of transgenic hUC-MSCs expressing TRAIL (named as untarget-TRAIL and target-TRAIL, respectively), or the non-transgenic hUC-MSCs (all 1×10⁶ cells per mouse) or PBS (named as WT-MSCs and PBS for negative control) respectively, and then monitored the changes of tumor signals by a small animal living imager every week for 3~4 weeks. 【Results】 After six passages to expand the cells, the both transgenic cell lines can stably express TRAIL gene. Their ratio of green fluorescent protein (GFP) positive cells can reach 93%-97%, and the positive ratio of their MSC-specific surface markers still maintained normal (CD34⁺, CD45⁺, and HLA-DR⁺ all <0.1%, CD90>99%, CD73>88%, and CD105 >60%). The median survival time (d) of U87MG-transplanted nude mice in the groups of untarget-TRAIL, target-TRAIL, WT-MSCs, and PBS was 41 vs 39 vs 24 vs 23(P<0.05). 【Conclusion】 The transgenic hUC-MSCs overexpressing TRAIL gene can significantly prolong the survival time of nude mice with brain glioma.

Objective:The aim of this study was to compare the efficacy and safety of iguratimod (IGU) or leflnomide (LEF) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods:This was a multicenter, randomized, double-blinded, double dummy and controlled clinical trial. Patients with moderate or high active RA were randomized in a 1∶1 ratio to receive IGU+MTX (Group A) or LEF+MTX (Group B) treatment. The efficacy and safety were assessed at week 12, 24 and 52, respectively. The primary endpoint was the American Colleague of Rheumatology 20 (ACR20) response rates at the 52th week. Pearson chi square test and two-way Analysis of Variance (ANOVA) were used to compare the improve- ment of ACR20 and DAS28 at 52 weeks. Pearson chi square test or Fisher exact probability test were used to compare the ACR 20 and ACR70 rate between the two groups after treatment. The measurement data of the two groups were compared by independent sample t-test or nonparametric test. Results:A total of 240 RA patients were enrolled in the present study. As a result, 84.1% and 81.0% of patients achieved ACR20 criteria at the 52th week in Group A and Group B, respectively ( χ2=0.35, P=0.56). And the ACR50/70 response rates, disease activity score 28 (DAS28), simplified disease activity index (SDAI) and the absolute decrease of DAS28 from baseline were not statistically different between the two groups at week 12, 24 and 52. The rates of adverse events were lower in Group A than those in Group B (60.0% vs 79.0%, P<0.01). The elevations of glutamic pyruvic transaminase/glutamic oxalacetic transaminase levels, concomitant use of hepatinica and white blood cell decrease were more common in Group B ( P<0.05). Conclusion:IGU in combination with MTX is an efficacious and safe treatment regimen, which is comparable in efficacy in control active RA but superior in safety to LEF combined with MTX.

Objective To explore the mediating effect of health belief on the relationship between health knowledge and health behavior among hypertensive patients with stroke.Methods The questionnaire of Stroke Knowledge Questionnaire (SKQ),Short Form Health Belief Model Scale (SF-HBMS)and health behavior scale for stroke patients (HBS-SP) were used to investigate the health knowledge,health belief and health behavior among 151 hypertensive stroke patients.The structural equation model was established using SPSS 17.0 and Mplus7.0 software.Results The total score of SKQ,SF-HBMS and HBS-SP were (86.23±.14.67),(4.26±0.54) and (3.01 ± 0.46).The Pearson r value for SKQ and SF-HBMS,SF-HBMS and HBS-SP,SKQ and HBS-SP were 0.516,0.603 and 0.449,respectively,P＜0.01.Health knowledge had no direct effect on health behavior.but had an indirect effect through health belief=0.338 (P＜0.01).The health knowledge has direct and positive effect on the health belief including perceived susceptibility,health motivation,and perceived benefit to health behaviors;the health belief of perceived seriousness to stroke has direct and positive effect on the health behavior,while perceived barrier has direct and negative effect on the health behavior,all P＜0.05.Conclusion The health belief has mediator effect between health knowledge and health behavior among hypertensive stroke patients.Stroke education efforts should be targeted at not only health knowledge but also health belief in order to increase patients’health behavior so as to prevent secondary stroke.

Objective To assess the filtration efficiency of two N95 filtering-facepiece respirators(FFRs)for the decomposition products of sulfur hexafluoride (SF6).Methods Two types of N95 FFRs (the particulate and the acid-proof respirators) were selected in this study.The decomposition products of SF6,including particles,hydrogen fluoride (HF) and sulfur dioxide (SO2),were measured under experimental condition by using TSI PortaCount Plus,fluorine ion-selective electrodes and spectrophotometer separately.The filtration efficiency was then calculated and compared.Results Both two models of N95 respirators had lowest filtration efficiency larger than 95％ for particles under airflow ranged from 10 to 95 L/min.When exposed to different concentrations of HF (low:0.00～ 1.99 mg/m3,middle:2.00～3.99 mg/m3,high:＞4 mg/m3),the acid-proof N95respirator was more effective than the particulate respirator (P＜0.05) with a filtration efficiency of 98.83％,99.08％,and 99.03％ versus 48.44％,45.71％,and 47.31％.For four SO2 concentration ranges (0.00～2.49 mg/m3,2.50～4.99 mg/m3,5.00-9.99 mg/m3,and ＞10.00 mg/m3),the acid-proof respirator showed a high filtration efficiency within exposure to 1.5 hours:95.73％,98.67％,98.14％,and 97.78％,respectively,when exposure duration extended to 4 hours,the filtration efficiency of the acid-proof respirator decreased to 91.97％,82.28％,70.12％,and 58.56％,respectively.Conclusion Both the particulate and the acid-proof N95 FFRs met national standards on the particulate filtration efficiency.The acid-proof N95 respirator demonstrates to be more effective in filtering HF and SO2 than the particulate respirator.The filtration efficiency could decrease to an unsafe condition under longer exposure duration,timely replacement of respirator is recommended at the workplace.

Objective To assess the filtration efficiency of two N95 filtering-facepiece respirators(FFRs)for the decomposition products of sulfur hexafluoride (SF6).Methods Two types of N95 FFRs (the particulate and the acid-proof respirators) were selected in this study.The decomposition products of SF6,including particles,hydrogen fluoride (HF) and sulfur dioxide (SO2),were measured under experimental condition by using TSI PortaCount Plus,fluorine ion-selective electrodes and spectrophotometer separately.The filtration efficiency was then calculated and compared.Results Both two models of N95 respirators had lowest filtration efficiency larger than 95％ for particles under airflow ranged from 10 to 95 L/min.When exposed to different concentrations of HF (low:0.00～ 1.99 mg/m3,middle:2.00～3.99 mg/m3,high:＞4 mg/m3),the acid-proof N95respirator was more effective than the particulate respirator (P＜0.05) with a filtration efficiency of 98.83％,99.08％,and 99.03％ versus 48.44％,45.71％,and 47.31％.For four SO2 concentration ranges (0.00～2.49 mg/m3,2.50～4.99 mg/m3,5.00-9.99 mg/m3,and ＞10.00 mg/m3),the acid-proof respirator showed a high filtration efficiency within exposure to 1.5 hours:95.73％,98.67％,98.14％,and 97.78％,respectively,when exposure duration extended to 4 hours,the filtration efficiency of the acid-proof respirator decreased to 91.97％,82.28％,70.12％,and 58.56％,respectively.Conclusion Both the particulate and the acid-proof N95 FFRs met national standards on the particulate filtration efficiency.The acid-proof N95 respirator demonstrates to be more effective in filtering HF and SO2 than the particulate respirator.The filtration efficiency could decrease to an unsafe condition under longer exposure duration,timely replacement of respirator is recommended at the workplace.