Objective:To observe the influence of methylprednisolone in the respiratory mechanical parameters in the elderly patients undergoing major surgeries with general anesthesia intubation after mechanical ventilation,and to investigate whether methylprednisolone can improve the respiratory system degenerative diseases and benefit the mechanical ventilation. Methods:Sixty patients undergoing elective line laparotomy were divided into experimental group and conrol group (n=30) according to their wishes.The patients in experimental group receieved intravenous injection of methylprednisolone 1 mL (40 mg) after endotracheal intubation,and the patients in control group receieved 1 mL intravenous saline water injection.The airway peak pressure (Ppeak), airway platform (Pplat), lung compliance (Compl), and airway resistance (Raw) of the patients in two groups were recorded at the time of immediately before administration and 10,20,30,40 min after administration.The arterial blood oxygen partial pressure(PaO2),arterial blood CO2 partial pressure(PaCO2),CO2 partial pressure at the end of breathe out(PetCO2) of the patients were detected at the time of immediately before administration and 20 min after administration.Results:Compared with before administration, the respiratory mechanics parameters of the patients in control group 10,20,30,40 min after administration had no statistically significant differences (P>0.05);the Comple of the patients in experimental group was singnificantly increased (P<0.05), and the Ppeak, Pplat,and Raw were significantly decreased (P<0.05).Compared with control group, the Compl of the patients in experiment group 10,20,30,and 40 min after administration were significantly increased (P<0.05),and the Ppeak, Pplat, and Raw were decreased (P<0.05).Compared with before administration,the PaO2,PaCO2,and PetCO2 of the patients in control group 20 min after administration had no significant differences(P>0.05);the PaCO2 and PetCO2 of the patients in experimental group 20 min after administration were decreased(P<0.05),and the PaO2 was increased(P<0.05).Compared with control group,the PaCO2 and PetCO2 of the patients in experimental group 20 min after administration were decreased(P<0.05),and the PaO2 was increased(P<0.05).Conclusion:Methylprednisolone can obviously reduce PaCO2,Peak, and Pplat and increase PaO2 and Compl;methylprednisolone has possibility in improving the adverse effects of degenerative disease of respiratory system on general anesthesia in the elderly patients.

Objective This study was conducted to analyze the clinical characteristics and pituitary function of patients with primary empty sella (PES).Methods The clinical data from 123 hospitalized adult patients with PES from January 2010 to May 2016 were retrospectively studied.Results (1) The average age of the 123 (male 43,female 80) PES patients was (59.2 ± 13.6) years (ranging 24-92 years),among whom 61％ patients were in the age group between 50-69 years.(2) The symptoms of the patients included fatigue (56.1％),headache (34.1％),nausea and vomiting (17.9％),gonadal dysfunction (17.1％),visual disturbance (5.7％) and hypopituitarism crisis (3.3％).(3) Hypopituitarism was found in 66 of the 123 patients.Among them,36.6％,31.7％ and 17.1％ were central hypoadrenalism,hypogonadism,and hypothyroidism,respectively.The percentage of hypopituitarism in complete PES was significantly higher than that in partial PES (P ＜ 0.05).(4) Sixteen patients were concomitant with other autoimmune diseases including 11 patients with Graves' disease and 2 with Cushing's syndrome due to adrenal adenoma.Conclusions The incidence of hypopituitarism in PES was 53.7％,in which the pituitary-adrenal axis hypofunction was more common.An overall evaluation of the pituitary function was essential for the patients who had headache and fatigue,or with suspected PES.The patients with hypopituitarism should be given hormone replacement therapy in time and followed up afterword.

Objective:To analyze the difference in skin surface lipids (SSL) between facial skin lesions of neonates with acne and normal facial skin of healthy infants.Methods:SSL samples were collected from facial skin lesions of 36 neonates with acne (acne group) and normal facial skin of 36 healthy infants (control group) at the Department of Dermatology, Children′s Hospital, Capital Institute of Pediatrics from June 2018 to August 2018. A lipid map was constructed by ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-QTOF-MS), and specific information about lipid components was obtained by multivariate data analysis. Independent-sample t test was performed with SPSS19.0 software for comparisons between 2 groups. Results:Compared with the control group, the acne group showed significantly increased relative content of glycerolipids and prenol lipids on the facial skin surface (both P < 0.001), but significantly decreased relative content of fatty acids, glycerophospholipids, sphingolipids, sterol lipids, saccharolipids and polyketides ( P < 0.01 or 0.05) .Further analysis showed that the average relative content of total lipids, diglycerides, wax esters and squalene was significantly higher in the acne group than in the control group ( P < 0.001 or 0.05), but the average relative content of linoleic acid was significantly lower in the acne group than in the control group ( P < 0.001) . Conclusion:Compared with the facial skin of healthy infants, the facial skin lesions of neonates with acne showed significantly increased total lipid content and different lipid components.

Objective:To observe the repairing effect of ozone water injection in the articular cavity for the treatment of knee osteoarthritis (KOA) on articular cartilage and to explore its repair mechanism.Methods:48 rats were randomly divided into fourgroups, the normal, model, normal saline and ozone water group, each group had 12 rats. The rats were injectied into the joint cavity with papain to establish a KOA model other than the normal group. After confirming the success of the model, the ozone water group and normal saline group was treated with ozone water and normal saline injection into the joint cavity once a week for a total of 3 treatments, the normal group and the model group are all raised routinely. Before and after the treatment, the ratknee joint behavioral score MG score was conducted; after the treatment articular cartilage surface gross score, hematoxylin and eosin (HE) staining and modified Mankin score of articular cartilage pathological changes was measured, and Western blot and Rt-PCR to measure the level of protein and mRNA expression of NF-κB p65, IKKβ and IκBα in articular cartilage tissues.Results:Compared with before the treatment, the rat knee joint behavioral score of the ozone water group was significantly lower (all P<0.05); after the treatment, the gross articular cartilage surface score and the modified Mankin score of the ozone water group were significantly reduced compared with the model and normal saline group (all P<0.05); Compared with the model and normal saline group, the protein and mRNA expression levels of NF-κB p65 and IKKβ in the ozone water group are significantly lower (all P<0.05), and the levels of IκBα are significantly higher (all P<0.05). Conclusion:Ozone water injection in the articular cavity can effectively repair damaged articular cartilage. The repair mechanism may be achieved by inhibiting the activation of NF-κB signaling pathway.

ObjectiveTo visually analyze the research hotspots and future development trends in the field of rehabilitation of chronic respiratory diseases domestic and overseas in the last decade. MethodsLiteratures about rehabilitation of chronic respiratory disease from 2011 to 2021 were retrieved. The Physiotherapy Evidence Database (PEDro) was used to access the quality of the literatures, and CiteSpace 5.8.R3 was used to analyze the number of publications and keywords. ResultsA total of 2 477 English articles and 3 308 Chinese articles were included. The overall volume of literature published in the field of rehabilitation of chronic respiratory diseases domestic and overseas showed a fluctuating increase. A total of 63 English articles met the requirement of medium-high quality with a score of four to nine on the PEDro scale, and the overall average score was 5.44. A total of 78 domestic articles scored five to eight, and the overall average score was 5.21. Domestic research in this field mainly focused on the pulmonary rehabilitation methods for patients with chronic obstructive pulmonary disease (COPD) and their effects on patients' quality of life and lung function, the process of development of heart-related diseases complicated by COPD, and the effects of nursing interventions, community rehabilitation and health education for chronic respiratory diseases, and exploration of precise pulmonary rehabilitation assessment, etc. In contrast, foreign countries mainly studied the physical activity and exercise capacity of patients with chronic respiratory diseases, emphasizing the self-management of patients, and focused on the cross-sectional research of other diseases such as combined aortic stenosis, and made "physical activity" and "exercise" as the frontier of research. ConclusionOverseas pulmonary rehabilitation programmes involve a wide range of chronic respiratory diseases, requiring multidisciplinary teamwork, strengthening patient self-management at home and focusing on changes in physical activity, motor function and quality of life after exercise, while the focus is on pulmonary rehabilitation in hospitalized COPD patients, also including the role of traditional Chinese exercise in China.

ObjectiveTo analyze the risk factors of dementia among healthy elderly individuals in the middle of their lives. MethodsA total of 175 participants aged 55 to 75 from two communities in Beijing were included from July, 2021 to April, 2023. Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) related risk factors and other demographic data were collected. According to the CAIDE assessment, participants with scores ≥ 9 were as high-risk group, and those with scores < 9 were as low-risk group. They were evaluated with Stroop Color Word Test (SCWT), two elements 1-back task paradigm and the revised Trail Making Test (TMT); measured the grip strength, 30 s forearm flexion tests and five sit-to-stand tests; the average step speed and step length of a 10-meter walk were recorded. ResultsThe average total score of CAIDE was 9.86 in the high-risk group, and was 4.95 in the low-risk group. There was no difference in age between two groups (P = 0.188). There were differences in the proportion of participants of male, less than seven years' education, systolic blood pressure > 140 mmHg, cholesterol > 6.5 mmol/L, body mass index > 30 kg/m², and lack of physical activity between two groups (χ² > 3.116, P < 0.05). The grip strength (t = -4.174), walking speed (t = -2.414), SCWT accuracy (Z = -2.684) were all worse in the high-risk group than in the low-risk group (P < 0.05). Logistic regression analysis showed that walking speed (OR = 25.483), grip strength (OR = 1.133) and SCWT accuracy (OR = 37.430) were independent influencing factors of dementia (P < 0.05). ConclusionWeaker grip strength, slower gait speed and worse inhibitory control might be independent influencing factors of dementia.

Objective: To analyze the interactions between different structural types of volatile oil components (VOCs) and skin lipid molecules, and investigate the mechanism of volatile oil in Chinese materia medica (VOCMM) as penetration enhancers. Methods: In this study, 210 different structural types of VOCs were selected from the VOCMM penetration enhancer database, and the molecular docking experiments were conducted with three main lipid molecules of skin: ceramide 2 (CER2), cholesterol (CHL), and free fatty acid (FFA). Each VOC was docked individually with each lipid molecule. Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular structures. Nine specific pathogen-free (SPF) Sprague Dawley (SD) rats were randomly divided into Control, Nootkatone, and 3-Butylidenephthalide groups for in vitro percutaneous experiments, with three rats in each group. The donor pool solutions were 3% gastrodin, 3% gastrodin + 3% nootkatone, and 3% gastrodin + 3% 3-butylidenephthalide, respectively. The penetration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin (Q12, µg/cm²). Result: (i) Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA, and hydrogen bonded to the head group of CER2. Among them, sesquiterpene oxides showed the most pronounced binding affinity to CER2. The VOCs with 2 − 4 rings (including carbon rings, benzene rings, and heterocycles) demonstrated stronger binding affinity for three skin lipid molecules compared with the VOCs without intramolecular rings (P < 0.01). (ii) According to the cluster analysis, most of the VOCs that bond well to CER2 had 2 − 3 intramolecular rings. The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner. The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding. (iii) The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60 ± 25.09 µg/cm2, and the transdermal absorption of gastrodin was significantly increased in Nootkatone group (Q12 = 5 503.00 ± 1 080.00 µg/cm², P < 0.01).  The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide  group (Q12 = 495.40 ± 56.98 µg/cm², P > 0.05). (iv) The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2. Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper. This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers,  and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals ; Berberine/therapeutic use* ; Fatty Liver ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Necrosis

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins