Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100％in both groups,and that of anastomosis leakage after VE was 16.7％in the experimental group and 14.3％in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P＜0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P＜0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P＜0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

BACKGROUND: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. METHODS: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. RESULTS: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4 CONCLUSIONS The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4
Age Factors ; Blood Cell Count ; CD4 Lymphocyte Count ; COVID-19/pathology* ; Cough ; Dizziness ; Headache ; Humans ; Patient Discharge ; Recurrence ; Risk Factors

Objective To study the influence of halogenated hydroxyl-alkanes inhalation anesthetic on the determination of ethanol content in blood. Methods Halogenated hydroxyl-alkanes were analyzed by headspace gas chromatography with double column confirmatory detection method. The influence of halogenated hydroxyl-alkanes on determination of ethanol content in blood sample by headspace gas chromatography was explored under the different detection conditions of KB-BAC1/ KB-BAC2 and J&W DB-ALC1/DB-ALC2 gas chromatographic column. Results The retention time of sevoflurane and enflurane was similar to that of ethanol and tert butanol respectively when using the J&W DB-ALC1/DB-ALC2 gas chromatographic column, and interfered with the detection of ethanol content in blood; only J&W DB-ALC1 gas chromatographic column can separate the sevoflurane and ethanol components, so as to eliminate their influence on the detection of ethanol content in blood. When using KB-BAC1/KB-BAC2 gas chromatographic column, the retention time of sevoflurane, isoflurane and ethanol is similar, especially that of sevoflurane and ethanol, and sevoflurane obviously interferes with the determination of ethanol content in blood. Conclusion Halogenated hydroxy-alkanes interfere with determination of ethanol content in blood by headspace gas chromatography. The interference can be discriminated effectively by choosing the suitable chromatographic column and double column confirmatory detection.
Alkanes ; Anesthetics, Inhalation ; Ethanol ; Isoflurane ; Sevoflurane

BACKGROUND AND OBJECTIVE: Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice. METHODS: Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively. RESULTS: A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition. CONCLUSIONS In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Animals ; Dexamethasone/therapeutic use* ; Disease Models, Animal ; Kupffer Cells/physiology* ; Liver Failure, Acute/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 4, Group A, Member 1/physiology* ; Receptors, Glucocorticoid/physiology*

OBJECTIVE: To compare the predictive value of Ees/Ea in patients with pulmonary arterial hypertension based on right cardiac catheterization and cardiac magnetic resonance examination. METHODS: A total of 50 pulmonary arterial hypertension patients confirmed by right heart catheterization were retrospectively reviewed and followed up 2 years. The relationship between the baseline clinical data and survival prognosis of patients with pulmonary arterial hypertension were analyzed. The predictive value of baseline Ees/Ea for prognosis in patients with pulmonary arterial hypertension were compared. RESULTS: The Ees/Ea calculated by volume method was significantly correlated with the prognosis of patients with pulmonary arterial hypertension(OR =0.082, 95%CI 0.009-0.814, P=0.032). The two-year survival rate of group Ees/Ea>0.67 was significantly higher than that of Ees/Ea≤0.67(86.7% vs. 50%, P=0.003). Conclution Ees/Ea calculated by volume method is an independent influence factor of the survival prognosis of patients with pulmonary arterial hypertension. When Ees/Ea≤0.67, the patients with pulmonary arterial hypertension is more likely to deteriorate.