ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

AIM:To compare the efficacy and safety of early combination therapy with ranibizumab and dexamethasone intravitreal implants versus ranibizumab monotherapy for the treatment of macular edema secondary to retinal vein occlusion(RVO-ME).METHODS: A retrospective cohort study was conducted on a total of 62 cases(64 eyes)of patients who were first diagnosed with RVO-ME at the Eye Centre of the Affiliated Hospital of Shandong Second Medical University between February 2022 and February 2023. The subjects were divided into two groups according to the different treatment regimens: 32 cases(34 eyes)in the monotherapy group received only ranibizumab [3+pro re nata(PRN)regimen], and 30 cases(30 eyes)in the combination therapy group were injected with ranibizumab once first, followed by dexamethasone intravitreal implant 3 wk later(1+DEX regimen). The best corrected visual acuity(BCVA), central retina thickness(CRT), foveal avascular zone(FAZ)area, macular vascular density(MVD)at the level of the deep vascular complex(DVC)of the retina, the incidence of ocular adverse effects, the number of drug injections, and the total cost between the two groups were compared before and after treatment.RESULTS: At 3 wk, 3 and 6 mo, and at the final follow-up of the two groups of patients, the improvement in BCVA, CRT, and MVD in the DVC layer was significantly better than that before treatment(all P<0.05); there were differences in the comparisons of BCVA and CRT between the two groups at 6 mo and the final follow-up(all P<0.05), and the increase in the number of letters of BCVA was the most pronounced in the combination therapy group at 6 mo of treatment. Statistical significant difference was observed in the comparison of MVD in the DVC layer between the two groups at 3 and 6 mo after treatment and at the final follow-up(all P<0.05). However, no significant change in FAZ area was evident before and after treatment in both groups(P>0.05). The combination therapy group exhibited a reduced number of injections and total cost in comparison to the monotherapy group. The combination therapy group exhibited a slightly higher incidence of high intraocular pressure and cataract progression compared to the monotherapy group, with no statistical significant difference(all P>0.05). Furthermore, no serious adverse events were observed in either group following treatment.CONCLUSION:Compared with ranibizumab alone, ranibizumab combined with dexamethasone intravitreal implant significantly improved vision, reduced macular edema, and lowered the frequency of injections and total treatment cost in patients with RVO-ME. CRT and MVD in the DVC layer are reliable prognostic indicators for patients with RVO-ME.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

This article presents the diagnosis and treatment processes, and morphological and genetic testing of Gongylonema pulchrum in a case with G. pulchrum found in the oral mucosa. In addition, this article reviews publications pertaining to G. pulchrum human infections by Chinese scientists during the recent 10 years and summarizes the demographic and clinical characteristics, location and number of parasites, diagnosis and treatment processes, and epidemiological surveys of cases infected with G. pulchrum, so as to provide insights into improving the diagnostic capability among clinicians.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

This article reports a patient with hepatic coma who underwent artificial liver support therapy and liver transplantation successfully， and the patient recovered well in the later stage after active treatment. This article also discusses the timing of liver transplantation.