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.

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 compare the clinical outcomes of thoracic endovascular aortic repair (TEVAR) using self-radiopaque marker guided physician modified fenestration with stent-graft in situ fenestration technology with or without the implantation of branch stents for the treatment of aortic arch diseases.Methods:The clinical data of 653 patients with aortic arch diseases who underwent TEVAR using fenestration from Dec 2015 to Jun 2023 at two vascular surgery centers were retrospectively analyzed.Results:A total of 454 patients received branch stent implantation, while 199 did not. The incidence of non-aortic-related complications within 30 days post-operation was higher in the branch stent implantation group compared to the non-implantation group (8.6% vs. 3.5%, P=0.020). The overall follow-up rate was 93.8%, with median follow-up time of 37 months and 52 months for the branch stent implantation group and non-implantation group, respectively. Kaplan-Meier survival analysis showed no significant statistical difference between the two groups in terms of cumulative all-cause survival ( P=0.223), free from endoleak ( P=0.106), and free from branch artery occlusion ( P=0.130). Conclusions:The implantation of branch stents following in situ fenestration with stent-graft technology in TEVAR did not significantly affect overall survival, endoleak incidence, or branch artery occlusion rates in patients with aortic arch diseases. Therefore, the decision to implant branch stents should be tailored according to the specific pathology and anatomical characteristics of the aortic arch.

Objective:To compare the clinical outcomes of thoracic endovascular aortic repair (TEVAR) using self-radiopaque marker guided physician modified fenestration with stent-graft in situ fenestration technology with or without the implantation of branch stents for the treatment of aortic arch diseases.Methods:The clinical data of 653 patients with aortic arch diseases who underwent TEVAR using fenestration from Dec 2015 to Jun 2023 at two vascular surgery centers were retrospectively analyzed.Results:A total of 454 patients received branch stent implantation, while 199 did not. The incidence of non-aortic-related complications within 30 days post-operation was higher in the branch stent implantation group compared to the non-implantation group (8.6% vs. 3.5%, P=0.020). The overall follow-up rate was 93.8%, with median follow-up time of 37 months and 52 months for the branch stent implantation group and non-implantation group, respectively. Kaplan-Meier survival analysis showed no significant statistical difference between the two groups in terms of cumulative all-cause survival ( P=0.223), free from endoleak ( P=0.106), and free from branch artery occlusion ( P=0.130). Conclusions:The implantation of branch stents following in situ fenestration with stent-graft technology in TEVAR did not significantly affect overall survival, endoleak incidence, or branch artery occlusion rates in patients with aortic arch diseases. Therefore, the decision to implant branch stents should be tailored according to the specific pathology and anatomical characteristics of the aortic arch.

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.

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.

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 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.