Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Objective To design a pH-sensitive nintedanib liposomes(Nb-Lips)which targeted the acidic microenvironment of pulmonary fibrosis.The entrapment efficiency(EE%)was optimized by the formulation process.Methods Nintedanib liposomes were prepared by membrane hydration method,and the formulation of nintedanib liposomes were optimized by single factor experiments and response surface method(RSM).The particle size,polymer dispersity index(PDI),Zeta potential and encapsulation rate was investigated by dynamic light scattering technique and microcolumn centrifugation method.The release behavior of nintedanib liposomes in artificial lung fluid with pH 7.4 and artificial lung fluid with pH 5.3 was investigated by dialysis method.Nintedanib liposomes were atomized with a compressed air atomizer and its atomization stability and aerodynamic particle size were investigated.Results The particle size of nintedanib liposomes was(100.651±7.315)nm,the PDI was(0.328±0.026),the zeta potential was(21.633±2.004)mV,and the encapsulation rate was higher than 80%.Compared with nintedanib solution at pH 7.4,the total release of nintedanib liposomes in pH 5.3 artificial lung solution was 60.78%higher,and the release of nintedanib liposomes in pH 5.3 artificial lung solution was 48h delayed,which was much higher than that of nintedanib solution.The data reveals no significant differences in particle size,potential and PDI before and after atomization of nintedanib liposomes,and the encapsulation rate decreased 4.25%.The fine particle fraction of the atomized droplets was 37.49%.Conclusion The response surface method can effectively improve the encapsulation rate of nintedanib liposomes,and successfully prepare nintedanib liposomes that are sensitive to acidic environment,and can be inhaled and released slowly.

A rapid analytical method for simultaneous determination of 32 kinds of multi-residue veterinary drugs in eggs was developed using a modified QuEChERS technique based on a reduced graphene oxide-coated melamine sponge(r-GO@MeS)by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The influences of graphene oxide(GO)concentrations,sponge dosages,and purification modes on drug recoveries were investigated during the purification process.The optimal purification conditions involved using a GO concentration of 0.5 mg/mL,a sponge dosage of 6.0 cm3/mL,and a dynamic purification mode of 5 extrusion cycles.Separation was achieved using an Agilent Eclipse Plus C18 RRHD column(100 mm×2.1 mm,1.8 μm),and quantitative analysis was performed by the external standard method using an electrospray ionization source(ESI)in multiple reaction monitoring(MRM)mode.The results showed that all 32 kinds of veterinary drugs exhibited good linear correlation with coefficients greater than 0.999,and matrix effects(MEs)ranging from?7.8%to 18.9%.The limits of detection(LODs)and quantification(LOQs)ranged from 0.2 to 10.2 μg/kg and from 0.6 to 28.0 μg/kg,respectively.The recoveries for the three spiked levels were in the range of 66.5%?117.5%,with intra-day and inter-day precision(Relative standard deviation)below 13.3%and 16.3%,respectively.The synthetic r-GO@MeS exhibited efficient matrix purification without the need of high-speed centrifugation or strong magnetic field assistance.This significantly shorted the sample pretreatment time and improved the convenience of the matrix purification process.Combined with UPLC-MS/MS,the method was suitable for the rapid determination of multi-residue veterinary drugs in eggs.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objective:To study the feasibility of domestic flow diverter(TFD) for the treatment of unruptured internal carotid artery small- and medium-sized wide-neck aneurysms.Methods:This is a retrospective case series study.The study retrospectively evaluated consecutive 54 patients with unruptured intracranial small- and medium-sized wide-neck aneurysms treated with TFD in the Department of Cerebrovascular Disease,the Second Affiliated Hospital of Kunming Medical University between October 2019 and January 2024. There were 11 males and 43 females, and the age of patients was (54.9±9.6) years (range:36 to 74 years). There were 63 aneurysms in 54 patients,6 of which were tandem multiple small aneurysms. One case had saccular aneurysms of bilateral internal carotid artery. The maximum diameter of aneurysm was (4.1±0.8) mm (range: 1.5 to 10.0 mm).The ratio of the maximum diameter of the aneurysm to the neck width diameter was 1.3±0.4 (range:0.4 to 2.4). The surgical and follow-up data were collected. The aneurysm embolization rate at the immediate operation and follow-up,and the complications were analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade D as complete occlusion and grade C and above (C1,C2,C3 and D) as successful occlusion. Clinical outcomes of all patients were evaluated by modified Rankin scale(mRS).Results:For 63 aneurysms, 48 aneurysms were treated with TFD alone,and 15 aneurysms were treated with a combination of TFD and coiling. The immediate postoperative successful occlusion rate was 14.3% (9/63) and the complete occlusion rate was 3.2% (2/63). Follow-up results were obtained for all of the patients. The follow-up time ( M(IQR)) was 124 (182) days (range: 85 to 754 days). The time to aneurysm successful occlusion was 140.5 (151.5) days (range: 85 to 308 days). At final follow-up,the successful aneurysm occlusion rate was 68.3% (43/63) and the complete occlusion rate was 58.7% (37/63). The complete occlusion rate of the TFD group was 50.0% (24/48) and the TFD+coiling group was 13/15. All patients had no aneurysm rupture,ischemic complications and no recurrence of the aneurysm needed to retreatment during the intraoperative and follow-up period. A total of 3 mild haemorrhagic complications which were related to dual-antiplatelet agents. Twelve patients had asymptomatic mild-moderate stent stenosis. TFD covered 66 branch vessels totally. Only 6 branches were affected by the time of the last follow-up and none of the patients had relevant ischaemic symptoms. All of 54 patients were evaluated as mRS score<2 points at the last follow-up. Conclusion:Using TFD to treat internal carotid artery unruptured small and medium-sized wide-neck aneurysms can simplify the surgical procedure with low complication rate, which is a clinically optional treatment approach.

The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.

Objective:To study the feasibility of domestic flow diverter(TFD) for the treatment of unruptured internal carotid artery small- and medium-sized wide-neck aneurysms.Methods:This is a retrospective case series study.The study retrospectively evaluated consecutive 54 patients with unruptured intracranial small- and medium-sized wide-neck aneurysms treated with TFD in the Department of Cerebrovascular Disease,the Second Affiliated Hospital of Kunming Medical University between October 2019 and January 2024. There were 11 males and 43 females, and the age of patients was (54.9±9.6) years (range:36 to 74 years). There were 63 aneurysms in 54 patients,6 of which were tandem multiple small aneurysms. One case had saccular aneurysms of bilateral internal carotid artery. The maximum diameter of aneurysm was (4.1±0.8) mm (range: 1.5 to 10.0 mm).The ratio of the maximum diameter of the aneurysm to the neck width diameter was 1.3±0.4 (range:0.4 to 2.4). The surgical and follow-up data were collected. The aneurysm embolization rate at the immediate operation and follow-up,and the complications were analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade D as complete occlusion and grade C and above (C1,C2,C3 and D) as successful occlusion. Clinical outcomes of all patients were evaluated by modified Rankin scale(mRS).Results:For 63 aneurysms, 48 aneurysms were treated with TFD alone,and 15 aneurysms were treated with a combination of TFD and coiling. The immediate postoperative successful occlusion rate was 14.3% (9/63) and the complete occlusion rate was 3.2% (2/63). Follow-up results were obtained for all of the patients. The follow-up time ( M(IQR)) was 124 (182) days (range: 85 to 754 days). The time to aneurysm successful occlusion was 140.5 (151.5) days (range: 85 to 308 days). At final follow-up,the successful aneurysm occlusion rate was 68.3% (43/63) and the complete occlusion rate was 58.7% (37/63). The complete occlusion rate of the TFD group was 50.0% (24/48) and the TFD+coiling group was 13/15. All patients had no aneurysm rupture,ischemic complications and no recurrence of the aneurysm needed to retreatment during the intraoperative and follow-up period. A total of 3 mild haemorrhagic complications which were related to dual-antiplatelet agents. Twelve patients had asymptomatic mild-moderate stent stenosis. TFD covered 66 branch vessels totally. Only 6 branches were affected by the time of the last follow-up and none of the patients had relevant ischaemic symptoms. All of 54 patients were evaluated as mRS score<2 points at the last follow-up. Conclusion:Using TFD to treat internal carotid artery unruptured small and medium-sized wide-neck aneurysms can simplify the surgical procedure with low complication rate, which is a clinically optional treatment approach.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

OBJECTIVE: To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. METHODS: Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. RESULTS: Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01). CONCLUSIONS WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.