Objective To explore the effect of enhanced recovery after surgery(ERAS)nursing combined with isokinetic muscle strength visual feedback training on postoperative patients with knee joint injury.Methods A total of 100 patients with knee joint injury who were treated in 909th Hospital(Southeast Hospital Affiliated of Xiamen University)from May 2022 to May 2023 were selected as the subjects.According to a random number table method,the patients were divided into control group(n=50)and observation group(n=50).The control group received ERAS nursing,and observation group received isokinetic muscle strength visual feedback training on the basis of control group.The pain,knee function recovery,quality of life and complications of two groups were compared.Results At 1 day,1 month,3 months and 6 months after operation,the pain visual analogue scale scores of observation group were lower than those of control group(P＜0.05).At 6 months after operation,the scores of knee joint function scale and World Health Organization quality of life scale in two groups were higher than before operation,and observation group were higher(P＜0.05).The total incidence of complications in observation group was lower than chat in control group(P＜0.05).Conclusion ERAS nursing combined with isokinetic muscle strength visual feedback training can significantly reduce postoperative pain in patients with knee joint injury,effectively promote the recovery of knee joint function.

Objective To explore the application value of distortion product otoacoustic emission (DPOAE) and speech in noise(SIN) testing in occupational health surveillance of noise-exposed workers. Methods A total of 220 noise-exposed workers was selected as the study subjects using the convenient sampling method. The study subjects participated questionnaire survey, personal noise exposure assessment, acoustic immittance testing, pure tone audiometry (PTA), DPOAE and SIN testing. According to PTA results, workers were enrolled into a high-frequency hearing loss (HFHL) group and a non-HFHL group. Results The detection rate of HFHL among the study subjects was 41.4%, and the detection rate of speech-frequency hearing loss was 15.9%. Workers′ bilateral DPOAE response amplitudes and signal-to-noise ratios at frequencies of 2.0-8.0 kHz in the HFHL group were lower than those in the non-HFHL group (all P<0.05). The DPOAE amplitudes at frequencies of 1.0-8.0 kHz in both ears of the study subjects were negatively correlated with the PTA threshold (all P<0.01), and were negatively correlated with age (all P<0.01). The signal-to-noise ratio loss score was higher among worker in the HFHL group than in the non-HFHL group (P<0.01) and was positively correlated with PTA thresholds (P<0.05). Conclusion DPOAE and SIN testing can detect early cochlear outer hair cell impairment and reduction of noise-related speech recognition ability in noise-exposed workers and may serve as an effective supplementary tool to routine PTA in occupational hearing surveillance.

Objective To explore the effect of enhanced recovery after surgery(ERAS)nursing combined with isokinetic muscle strength visual feedback training on postoperative patients with knee joint injury.Methods A total of 100 patients with knee joint injury who were treated in 909th Hospital(Southeast Hospital Affiliated of Xiamen University)from May 2022 to May 2023 were selected as the subjects.According to a random number table method,the patients were divided into control group(n=50)and observation group(n=50).The control group received ERAS nursing,and observation group received isokinetic muscle strength visual feedback training on the basis of control group.The pain,knee function recovery,quality of life and complications of two groups were compared.Results At 1 day,1 month,3 months and 6 months after operation,the pain visual analogue scale scores of observation group were lower than those of control group(P＜0.05).At 6 months after operation,the scores of knee joint function scale and World Health Organization quality of life scale in two groups were higher than before operation,and observation group were higher(P＜0.05).The total incidence of complications in observation group was lower than chat in control group(P＜0.05).Conclusion ERAS nursing combined with isokinetic muscle strength visual feedback training can significantly reduce postoperative pain in patients with knee joint injury,effectively promote the recovery of knee joint function.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective : The purpose of this study was to investigate the effect of different exposure sequence and interval on the post-antibiotic effect(PAE) and 24-hour time-kill produced by linezolid and fosfomycin in combination againstStaphylococcus aureus(S.aureus). Methods: PAEs were evaluated by exposingS.aureusto linezolid and fosfomycin individually and simultaneously for 1 h.Further assess of PAEs with the organism exposed first to linezolid for 1 h, followed by a second 1 h fosfomycin exposure at the beginning(Tb),middle(Tm)and end(Te) of the PAE phase induced by linezolid.The next study was similar to the above, but with the sequence of the two antibiotics reversed, i.e.fosfomycin then linezolid.The 24-hour time-kill studies were performed with three exposure regimens: simultaneous exposure of the two antibiotics; first exposure to linezolid for 1 h and then combined with fosfomycin, and first exposure to fosfomycin for 1 h and then combined with linezolid to draw the sterilized curve. Results: Compared with the PAE of individual antibiotics [ linezolid(1.2±0.1) h, fosfomycin(1.6±0.1) h],the PAE produced by simultaneous exposure of the combination(2.9±0.1) h presented additive interaction.However, the PAE of fosfomycin decreased or even disappeared(-0.3 h for Tb, 0 h for Tm and 0.9 h for Te) during the PAE phase of linezolid, and with a stronger antagonism at the beginning.Differently, an additive interaction was observed again when the test organism was exposed to fosfomycin first.In the 24-hour time-kill assays, the antibacterial effect of the first exposure to fosfomycin regimens was significantly stronger(difference of 1 log10)than that of the simultaneous exposure and the first exposure to linezolid, while the latter two were similar. Conclusion The pharmacodynamic behaviour of linezolid combined with fosfomycin againstS.aureuswas influenced by exposure regimen.The first exposure to fosfomycin regimens rather than simultaneous exposure may exert the optimal antibacterial activity.Therefore, the exposure regimen is one of the important factors to be considered for the clinical application of this combination.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective:To investigate the clinical management value of chitinase 3-like 1 protein(CHI3L1) in hepatocellular carcinoma (HCC) by studying the expression of CHI3L1 in peripheral blood, liver cancer and paired adjacent non-tumor tissues.Methods:Retrospective study. From 2013 to 2017, 405 patients with HCC in Third Affiliated Hospital of Naval Medical University were enrolled into the study. Meanwhile, 112 patients with liver cirrhosis (LC), 114 health subjects were included as disease and health controls. CHI3L1 in peripheral blood was detected by ELISA kit. Tissues array was made by collecting 90 pairs of tumor tissues and matched paracancer tissues, from HCC patients who were conformed by pathology. The expression of CHI3L1 in HCC tissues was analyzed by immunohistochemistry. Differences between independent groups were tested by Mann-Whitney U test or Kruskal Wallis H test, Pearson correlation analysis was used for analyzing the relationship between two subjects, and matched rank sum test was used for cancer tissue and adjacent tissue comparison. Results:The median (quartile) of CHI3L1 protein in LC group, HCC group and NC group was 195.8 (103.3,330.4) μg/L,118.2 (74.9,201.0) μg/L,46.8 (30.7,66.4) μg/L independently. The protein level of CHI3L1 in LC group was significantly higher than that in HCC group and health control group ( Z=5.186,12.928, P<0.001). HCC group was significantly higher than that in health control group ( Z=10.788, P<0.001). The level of CHI3L1 in HCC group was not related to whether liver cirrhosis was accompanied ( Z=-0.286, P=0.775). The level of serum CHI3L1 was positively correlated with noninvasive fibrosis markers (HA, PⅢNP, Ⅳ-C, FIB-4 index) ( r=0.202,0.159,0.299 and 0.221, P<0.05) and negatively correlated with ALB( r=-0.326, P<0.05) while positively correlated with AST and PT( r=0.138, 0.160, P<0.05). Positively correlation was observed between CHI3L1 and tumor size ( r=0.284, P<0.001). CNLC stage [CHI3L1 level in advanced group125.2(81.9,228.5)μg/L was higher than that in early group112.0(70.2,169.2)μg/L ( Z=-2.326, P=0.018)], but no correlation with microvascular invasion( Z=-1.531) and tumor capsule(χ 2=0.818, P>0.05). In 73 cases of HCC tissues, the positive rate of CHI3L1 was 78% (57/73) in cancer tissues and 83%(61/73) in paired adjacent non-tumor tissues. The staining intensity score of paracancer tissue 1.5(1.5,2.5) was higher than that of cancer tissue 1.5(1.5,2.0)( Z=-2.053, P=0.040). Conclusions:The tissue source of CHI3L1 protein in HCC includes cancer tissue and paracancerous tissue. The detection of serum CHI3L1 level is helpful to evaluate tumor load assessment and disease stratification management in HCC.

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin-isonicotinamide (MYR-INM) and myricetin-caffeine (MYR-CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure. The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer (CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR-INM (1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.