ObjectiveTo evaluate the therapeutic efficacy of acupuncture plus fumigating eyes with cool Chinese medicinal fog in treating severe dry eye syndrome (DES).MethodTwenty-six outpatients with moderate-severe DES patients were classified into 11 cases of heat damaging yin type (20 eyes) and 15 cases of phlegm-stagnation type (23 eyes), to simultaneously receive acupuncture and fumigating eyes with cool Chinese medicinal fog. Tear break-up time (BUT), tear production (SchirmerⅠtest, SIT), and subjective symptoms score were observed and analyzed before treatment, 1 month, 3 months, and 6 months after treatment.ResultThe SIT, BUT, and subjective symptoms score 1 month, 3 months, and 6 months after treatment were superior to that before treatment (P<0.01); The SIT, BUT, and subjective symptoms score 6 months after treatment were lower than that of 3 months after treatment (P<0.05) but still significantly different from that before treatment (P<0.05).ConclusionAcupuncture plus fumigating eyes with cool Chinese medicinal fog can improve the symptoms and signs of DES, though the therapeutic efficacy decreases during the long-term follow-up study.

Aim To investigate the effect of hesperidin on human lung cancer cell A549 and the possible mechanism.Methods The cell apoptosis and necrosis of A549 treated with hesperidin were measured by the Hoechst 33342/PI fluorescent dye based on microfluidic chip technology.Cell cycle and apoptosis rate were evaluated by flow cytometry(FCM).The expressions of the related genes were detected through the real-time fluorescent quantitative PCR technology(RT-PCR) including VEGF, PI3K and PTEN.The protein expressions of Bcl-2, Cyclin B1, PI3K, Akt and PTEN were detected by Western blot after hesperidin intervention.Results The proliferation of A549 cells was significantly inhibited by hesperidin in a dose-dependent manner.FCM results showed that hesperidin could not only influence the G0/G1 phase and S phase, but also promote the apoptosis of lung cancer cells.Meanwhile, the apoptosis and necrosis rate was increased from(6.7±0.6)% to(27.9±1.1)% compared with that of control group(P<0.05).From the level of molecular, the gene expressions of VEGF and PI3K were decreased, while the PTEN was increased after hesperidin stimulation.Western blot results showed that the expression of protein Bcl-2, Cyclin B1 and Akt were decreased, which all showed close relationship with cell apoptosis, cell cycle and PI3K-Akt signaling pathway.The expression of PI3K was increased, but the change of PTEN was not statistically significant compared with that of control group.Conclusion Hesperidin induces lung cancer cell apoptosis through PI3K-Akt signaling pathway, which blocks cancer cell division and destroys the balance of related protein expression.

Biomimetic nano formulations of biofilms have low immunogenicity, high targeting, and good biocompatibility, and can avoid being cleared by the endothelial reticular system, thus with in longer blood circulation time in the body.This article mainly reviews the main types as well as advantages and disadvantages of biomimetic nano formulations of biofilms, including tumor cell membranes, red blood cell membranes, platelet membranes, white blood cell membranes, stem cell membranes, extracellular vesicles (exosomes, microvesicles, and apoptotic bodies), endoplasmic reticulum membranes, and composite biofilms, with also a prospect of the challenges facing biomimetic nano formulations of biofilms and their future development based on their current research status, aiming to provide some insight for further research on biomimetic nano formulations of biofilms.

Objective To explore the mechanism of Jiawei Bazhen Yimu Capsule on premature ovarian failure rats from the perspective of metabolomics.Methods Female SD rats were randomly divided into sham operation group,model group and Jiawei Bazhen Yimu Capsule low,medium and high dose groups,with 10 rats in each group.The model of premature ovarian failure was replicated by removing bilateral ovaries of rats and administered intragastrically once a day for 21 days.The serum samples of rats in each group were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UPLC-Q-TOF-MS).Combined with multivariate statistical analysis,the effects of Jiawei Bazhen Yimu Capsule on differential metabolites in rats with premature ovarian failure were investigated.The differential metabolites identified by MELIN database or KEGG database were imported into Metaboanalyst 5.0 online platform for metabolic pathway analysis.Results A total of 18 potential differential metabolites were screened and identified.Most of the differential metabolites showed a good callback trend after intragastric administration of Jiawei Bazhen Yimu Capsule.These 18 differential metabolites were enriched into 2 metabolic pathways(Pathway Impact>0.1),which were glycerophospholipid metabolism and arachidonic acid metabolism pathways.Conclusion The therapeutic effect of Jiawei Bazhen Yimu Capsule on premature ovarian failure may be related to improving the level of differential metabolites in serum and restoring normal metabolic activities in rats.

Objective To establish a"quality-quantity"double standard control method of Schizonepeta Spike based on the reference material without relying on multiple reference substances.Methods HPLC technology was used to establish the characteristic atlas of Schizonepeta Spike based on the reference traditional Chinese medicinal materials.The chemical constituents of common peaks were identified by Q-TOF-MS technology,and the authenticity of Schizonepeta Spike was determined by the similarity of characteristic peaks of the reference traditional Chinese medicinal materials and the tested traditional Chinese medicinal materials.The relative content of each characteristic peak in different batches of the tested traditional Chinese medicinal materials was calculated by accurate quantition of pulegone.The"Average value-Standard deviation"was taken as the lower limit of the relative content of characteristic peak chemical components relative to pulegone,and the quality of Schizonepeta Spike was determined according to the lower limit of the relative content of characteristic peak.Results The characteristic atlas and content determination method met the requirements of methodology investigation.A total of 11 common chromatographic peaks were determined,and 6 chemical components were identified,which were luteolin,hesperidin,luteolin-7-O-glucuronide,luteolin,geranyl,pulegone.The similarity between the tested traditional Chinese medicinal materials and reference traditional Chinese medicinal materials was greater than 0.90.The lower limit of relative content of chemical components of Schizonepeta Spike characteristic peak was defined.Conclusion The method can identify Schizonepeta Spike clearly and quickly without many reference substances,and provide reference for quality control of Schizonepeta Spike.

Objective:To evaluate the effect of long-term intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on the activation of hippocampal microglia in a mouse model of postoperative cognitive dysfunction (POCD).Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, were stratified according to body weight and divided into 4 groups ( n=24 each) by a random number table method: control diet group (group C), ω-3 PUFAs group (group ω), control diet plus POCD group (group C+ P) and ω-3 PUFAs plus POCD group (group ω+ P). Mice were fed a special ω-3 PUFAs diet (DHA 0.14 g/100 g, EPA 0.03 g/100 g) for 12 weeks in group ω and group ω+ P, while mice were fed with a control diet for 12 weeks in group C and group C+ P.Tibial fracture procedures were performed under isoflurane anesthesia to develop the POCD model after 12 weeks of feeding.The fear conditioning test and Y maze test were performed on 1st and 3rd days after developing the model.The mice were sacrificed after behavioral tests, and the hippocampal tissues were removed for determination of the contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (by gas chromatography-mass spectroscopy), density of Iba-1 positive microglia (by immunofluorescence staining), and expression of mature brain-derived neurotrophic factor (mBDNF) and precursor brain-derived neurotrophic factor (pro-BDNF) (by Western blot), and contents of interleukin-1beta (IL-1β) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test was increased, mBDNF/pro-BDNF ratio was increased ( P<0.05), no significant change was found in the rotation accuracy in Y maze test, density of Iba-1 positive microglia and contents of IL-1β and IL-6 in hippocampus ( P>0.05) in group ω ( P<0.05), and no significant change was found in the contents of DHA and EPA ( P>0.05), the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were decreased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were increased, and mBDNF/pro-BDNF ratio was decreased in group C+ P ( P<0.05). Compared with group C+ P, the contents of DHA and EPA were significantly increased, the percentage of freezing time in the contextual test and accuracy of rotation in Y maze test were increased on 1st and 3rd days after operation, the density of Iba-1 positive microglia and contents of IL-1β and IL-6 were decreased, and mBDNF/pro-BDNF ratio was increased in group ω+ P ( P<0.05). Conclusions:Long-term intake of ω-3 PUFAs can improve cognitive function in a mouse model of POCD, and the mechanism may be related to inhibition of activation of hippocampal microglia, reduction of inflammatory responses, and thus increasing the mBDNF/Pro-BDNF ratio.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.