ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD).Methods:A exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before.Results:Retinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow- white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up.Conclusion:Subretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.

Humans ; Soft Tissue Neoplasms ; Mesenchymoma/diagnostic imaging* ; Paraneoplastic Syndromes/pathology*

Objective:To observe the imaging features of fundus lesions associated with COVID-19.Methods:A observational case series study. Twenty eyes of 10 patients with fundus lesions associated with COVID-19 at Xiamen Eye Center of Xiamen University from December 10, 2022 to January 20, 2023 were included in this study. There were 1 males and 9 females, aged from 17 to 49 years, with the median age of 26 years. The time of ocular symptoms after the diagnosis of COVID-19 was 0-2 days. The time from the onset of ocular symptoms to seeing a doctor was 1-14 days. All patients were examined by best-corrected visual acuity (BCVA), intraocular pressure, color fundus photography, infra-red fundus photography (IR), optical coherence tomography (OCT). Serum D-dimer examination was performed in 3 patients. The median BCVA was 0.4. There was no abnormalities in intraocular pressure and anterior segment examination. Among 20 eyes of 10 patients, there were 10 eyes of 5 patients with acute macular neuroretinopathy (AMN), 6 eyes of 3 patients with Purtscher-like retinopathy (PLR), 4 eyes of 2 patients with central retinal vein occlusion (CRVO). The imaging features of fundus were observed and analyzed.Results:Retinal lesions included AMN, paramacular central medial retinopathy (PAMM), PLR, cotton wool spots, hemorrhage, optic disc edema, macular edema. AMN was found in 10 eyes, with reddish-brown and wedge-shaped lesion in the fovea, dark area in IR and hyper reflectivity in outer nuclear layer and outer plexiform layer by OCT. The cotton wool spot showed hyper reflectivity on retinal nerve fiber layer whereas PAMM showed band-shape hyper reflectivity in inner nuclear layer by OCT. The Purtscher spot was seen at the posterior pole and/or peripapillary in 6 eyes of PLR. By OCT examination, the retinal nerve fiber layer corresponding to Purtscher flecken was significantly thickened and the reflex was enhanced. Among 6 eyes of PLR, there were 4 eyes combined with AMN, 1 eye with PAMM and macular edema. In 4 eyes of CRVO, vitreous cells, optic disc edema, retinal flame, spot hemorrhage, and atypical cotton wool spots were seen in 2 eyes.Conclusions:The manifestations of fundus lesions associated with COVID-19 are varied. The multilayer structure of retina is involved, and the microvessels of retina and choroidal capillary layer are damaged.

OBJECTIVE: To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS). WETHODS: Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein. RESULTS: Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein. CONCLUSION The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.
DNA Mutational Analysis ; Exons ; Fibrillin-1 ; genetics ; Fibrillins ; Humans ; Marfan Syndrome ; genetics ; Mutation ; Pedigree

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.

Objective To explore the effects of hospital drug self-management training on medication compliance in patients with cardiovascular disease after discharge. Methods From March 2016 to February 2017, a total of 120 patients with cardiovascular disease in the Department of Internal Cardiovascular of Wuxi People's Hospital were selected and randomly divided into experimental group and control group, with 60 cases in each. The patients in the experimental group were trained with medication self-management mode, while the patients in the control group were treated in routine care. The scores of medication administration and the scores of 2 weeks, 1 month and half year after discharge were recorded, and the satisfaction of medication management and education mode were compared between the two groups. Results The scores of medication administration of 2 weeks, 1 month and half year after discharge, and the satisfaction of medication management and education mode after discharge 2 weeks were all higher than those of the control group (t=5.900, 7.058, 11.412, 4.693;P<0.001). Conclusions The hospital drugs self-management training can effectively improve the medication compliance in cardiovascular disease patients after discharge.

Atherosclerosis (As) is an important pathological basis of cardiovascular and cerebrovascular diseases. The pathogenesis studies of As have been a hot topic in the field of vascular biology research. The inflammation is known as a major participant in the development process of As. And monocyte-macrophage plays a central role in inflam-mation. In recent years, with the deepening research on inflammatory mechanisms, the As macrophage polarization is attracting researchers' attention. Under different environmental inductions, macrophages develop into M1 and M2 phenotypes. M1 macrophages (classical type), which can stimulate the secretion of pro-inflammatory cytokines, is generally considered as pro-inflammatory subtypes and can facilitate the progress of As. Whereas, M2 macrophages (alternative type), which can inhibit pro-inflammatory factor production, function as anti-inflammatory subtypes and likely to inhibit the progression of As. The mechanisms of As, macrophage polarization in As, and opportunities for herbal medicines will be summarized in this review.