ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

OBJECTIVE To explore the relationship between severe cardiotoxicity caused by oxaliplatin combined with capecitabine and genetic polymorphism， thereby providing references for safe clinical medication use. METHODS Clinical pharmacists conducted a correlation analysis on a case of severe cardiotoxicity in a rectal cancer patient at Qilu Hospital of Shandong University following first-time treatment with standard doses of oxaliplatin combined with capecitabine. Case reports of cardiotoxicity caused by oxaliplatin and capecitabine were retrieved from the Chinese and English databases such as CNKI and PubMed.Basic patient information， drug treatment plan， and cardiotoxic manifestations were extracted and summarized. Combined with the patient’s genetic polymorphism test results related to the metabolism and excretion of platinum-based and fluorouracil drugs， potential mechanisms and prevention strategies for cardiotoxicity induced by oxaliplatin and capecitabine were discussed. RESULTS The patient exhibited homozygous mutations in ABCB1 C3435T and G2677T/A， a heterozygous mutation in MTHFR A1298C， and a heterozygous mutation in GSTP1 A105G， indicating impaired metabolism and excretion of oxaliplatin and capecitabine. The pharmacists recommended discontinuing oxaliplatin and reducing capecitabine to 50% of the original dose for subsequent treatment. The physicians adopted this advice， and the patient experienced no further severe adverse reactions with stable disease progression. CONCLUSIONS Oxaliplatin and capecitabine may cause severe cardiotoxicity. Medical institutions with adequate resources should perform genetic polymorphism test related to drug metabolism and excretion in patients prescribed these agents. For patients with multiple gene mutations， close monitoring and appropriate dose reductions are recommended to ensure medication safety and efficacy.

Objective To explore the effect of Tianma Gouteng Yin combined with butylphthalein(NBP)on symptom improvement and vascular elasticity in patients with acute cerebral infarction(ACI).Methods Eighty-two ACI patients admitted to Lu'an Hospital of Traditional Chinese Medicine were included in this study,and they were randomly separated into the single group and the combination group,with 41 cases in each group.The single group was given intravenous infusion of NBP sodium chloride injection,and the combination group was given treatment with Tianma Gouteng Yin on the basis of the single group.Cerebrovascular reserve function,endothelial function,neurological function,independent living ability,hemodynamic indicators,vascular elasticity,clinical efficacy and incidence of adverse reactions were compared between the two groups of patients at 1 day after admission(T0)and 14 days after treatment(T1).Results There were no significant differences in cerebrovascular reserve function,endothelial function,National Institutes of Health Stroke Scale(NIHSS)scores,independent living ability scores,hemodynamic indicators and vascular elasticity indicators at T0 between the two groups(P＞0.05).At T1,levels of cerebrovascular reactivity(CVR),nitric oxide(NO),nitric oxide synthase(NOS),large artery elasticity index(C1)and small artery elasticity index(C2)were significantly increased in both groups,and levels were higher in the combined group than those of the single group(P＜0.05).At T1 moment,levels of ET-1,vascular endothelial growth factor(VEGF),NIHSS score,MRS score,red blood cell count,whole blood viscosity,platelet adhesion rate and arterial pressure were reduced in both groups,and levels were lower in the combined group than those of the single group(P＜0.05).The total effective rate was higher in the combination group(80.5%)than that of the single group(46.3%).The overall incidence of adverse reactions was lower in the combined group than that in the single group(P＜0.05).Conclusion Tianma Gouteng Yin combined with NBP can effectively improve the cerebral vascular reserve function,endothelial function and neurological damage in ACI patients,increase vascular elasticity and improve hemodynamic levels.

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Objective:To evaluate the efficacy and safety of a China-made disposable peroral cholangioscope in animal cholangioscopy.Methods:Six healthy Bama minipigs underwent the domestic disposable peroral cholangioscopy after anesthesia. The operation performance and image quality of the products were evaluated, and intraoperative and postoperative complications were recorded.Results:All 6 animals received the domestic disposable peroral cholangioscopy. The cholangioscope showed good operating performance and could smoothly enter the biliary tract through the duodenoscope. The water injection, suction and instrument channels were unobstructed. The cholangioscopic image was clear, the color resolution was good, and there was no image distortion. The lumen and the mucosal surface could be accurately assessed. During the examination, there was no operative injuries such as bleeding, perforation, or adverse events such as respiratory depression or cardiac arrest. All pigs survived the operation with no adverse reaction.Conclusion:The China-made disposable peroral cholangioscope is safe, with good operability and high-quality image.

OBJECTIVE：To study the m edical insurance budget impact analysis （BIA）guidelines or nomative documents of some European countries ，and to provide the suggestions for the formulation and implementation of medical insurance BIA guidelines in China. METHODS ：Medical insurance BIA guidelines or related documents in European countries such as Ireland ， France，Poland，Belgium and UK were retrieved to summarize and comparatively analyze the general analysis framework and special specification. The formulation of medical insurance BIA guideline in China and the suggestions were put forward. RESULTS & CONCLUSIONS ：The above-mentioned medical insurance BIA guidelines or documents of the five European countries generally study the impact of the cost of health technology on resources within 3-5 years from the perspective of budget holders. The analysis framework of the guidelines or documents is basically the same ，but the guidelines or documents are adjusted according to the characteristics of national health system in terms of the positioning of medical insurance BIA ，the scope of cost data inclusion ， model design ，population subgroup analysis and so on. For example ，Ireland had special requirements on cost data inclusion ， sensitivity analysis and data source ，while France had detailed regulations on medical insurance BIA model ，sensitivity analysis and presentation of medical insurance BIA results. Our country should pay attention to the role of medical insurance BIA in medical and health decision-making ，formulate China ’s medical insurance BIA guidelines to standardize empirical research ，and combine the characteristics of China ’s health system when formulate the guideline. It is suggested that China ’s medical insurance BIA guidelines should at least include research perspective ，research time limit and discount ，reference situation ，target population ， cost，market share ，data source ，uncertainty analysis and other overall framework or basic elements to ensure the smooth operation of medical and health funds.

Objective:To investigate the effects of different lymph node dissection methods in radical resection of intrahepatic cholangiocarcinoma (ICC) on the number of harvested lymph nodes and prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 57 patients with ICC who underwent radical resection in the Second Affiliated Hospital of Nanchang University from January 2011 to January 2016 were collected. There were 25 males and 32 females, aged from 45 to 72 years, with an average age of 59 years. Of the 57 patients, 36 undergoing en bloc fusion lymph node dissection and 21 undergoing conventional lymph node dissection were allocated into observation group and control group, respectively. Observation indicators: (1) intraoperative situations; (2) results of postoperative pathological examination; (3) postoperative complications; (4) follow-up. Follow-up using outpatient examination or telephone interview was performed once every six months after hospital discharge to detect survival of patients up to January 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was done using the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was analyzed by the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact propability. Comparison of ordinal data between groups was analyzed using the Mann-Whitney U test. The survival curve and rate were drawn and calculated using the Kaplan-Meier method, and survival of patients was analyzed by the Log-rank test. Results:(1) Intraoperative situations: operation time, volume of intraoperative blood loss, hepatic portal occlusion time, cases with <3 segments of hepatectomy and ≥3 segments of hepatectomy for the observation group were (218±53)minutes, (266±24)mL, (21±9)minutes, 5, 31, respectively, versus (207±45)minutes, (270±23)mL, (19±8)minutes, 2, 19 for the control group, showing no significant difference in the above indicators between the two groups ( t=-0.530, 0.774, 0.590, χ2=0.004, P>0.05). (2) Results of postoperative pathological examination: the number of harvested lymph nodes and percentage of positive lymph nodes of the observation group were 11±3 and 16.58%(66/398), respectively, versus 5±2 and 6.80%(7/103) of the control group, showing significant differences in the above indicators between the two groups ( t=-9.454, 2.148, P<0.05). (3) Postoperative complications: cases with Clavien-Dindo grade Ⅰ-Ⅱ complications or Clavien-Dindo grade Ⅲ-Ⅳ complications, cases with bile leakage, cases with postoperative hemorrhage, cases with incision infection, cases with gastroparesis were respectively 35, 1, 6, 1, 8, 0 in the observation group and 19, 2, 3, 1, 1, 2 in the control group. There was no significant difference in the cases with complications of Clavien-Dindo classification, cases with bile leakage, cases with incision infection between the two groups ( χ2=0.236, 0.000, 1.870, P>0.05) and no significant difference in the cases with postoperative hemorrhage, cases with gastroparesis between the two groups ( P>0.05). (4) Follow-up: 57 patients were followed up for 5-42 months, with a median time of 36 months. The survival time and postoperative 3-year survival rate were respectively 36 months (range, 8-42 months) and 66.7% of the observation group, versus 23 months (range, 5-39 months) and 38.1% of the control group, showing significant differences in the above indicators between the two groups ( Z=-2.253, χ2=5.317, P<0.05). Conclusion:For radical resection of ICC, the en bloc fusion lymph node dissection is beneficial to increase the number of harvested lymph nodes and improve survival rate of patients.

Objective： ：To explore a novel chimeric antigen receptor (CAR)-T cell treatment to treat Multiple Myeloma (MM) via target B cell maturation antigen (BCMA). Methods： ：A CAR-BCMA molecular was constructed based on mouse originated BCMA scFv, and was packaged into lentiviral vector and transfected into T cells from healthy donors to construct CAR-BCMA-T cells. The BCMApositive cell lines A549-BCMA, A549-BCMAOFP and K562-BCMA were constructed as target cells. Then, the CAR-BCMA-T cells were co-incubated with the constructed target cells and human myeloma U266 cells, and the cytotoxic effects of CAR-BCMA-T cells were evaluated via CCK-8 and FACS. Finally, the CAR-BCMA-T cells originated from MM patients were constructed, and its cytotoxicity against A549-BCMA were examined; in addition, the IFN-γ release level in CAR-BCMA-T cells was evaluated by ELISA and FACS. Results: After 11 days’incubation, the CAR-BCMA-T cells originated from healthy donors amplified 300 times with a positive rate of 43%. The BCMApositive target cell lines were constructed successfully. Under an effector : target ratio of 5:1, the killing rates of CARBCMA-T cells against A549-BCMA, K562-BCMA and U266 were about 80%, 60%, and 80%, respectively, which were significantly higher than those against BCMA negative cells; and the cytotoxicity was related to the BCMA expression level in target cells. What’ s more, at the effector : target ratio of 20:1, the CAR-BCMA-T cells originated from MM patients were demonstrated to exhibit a killing rate of more than 95% againstA549-BCMApositive cells, and produced large amount of IFN-γ. Conclusion: CAR-BCMA-T cells originated from both healthy and MM donors were successfully constructed, and they can effectively and specifically kill BCMA positive tumor cells.

Objective: To investigate the correlation between sleep quality and the use of smart phone before bed in middle school students, and to provide a reference for relevant prevention and control. Methods: A total of 3 749 students from 4 middle school which were randomly selected by stratified cluster sampling method were assessed with selfdesigned questionnaire for the students’ general information,smart phone usage before bed,as well as the Epworth Sleepiness Scale(ESS),and Insomnia Severity Index(ISI). Results: A total of 63.17% of students in the seventh grade used mobile phones before going to bed. 67.04% in the eighth grade, 81.18% in the ninth grade, 83.54% in the first grade of high school and 80.11% in the second grade of high school. Mobile phones usage before bed gradually increased with grade. Students with ≥2 h smart phone usage before bed(group 2) had higher scores than those with <2 h smart phone usage before bed(group 1) in each item of ESS, except dozing during traffic jam(P<0.01). The group 2 had higher scores than group 1 in ESS and ISI scores(P<0.01). Conclusion Smart phone usage before bed in middle school students is very common. The risk of sleep disorders increased with the duration of smart phone usage before bed. Parental supervision should be involved in the intervention of smart phone usage before bed among middle school students.