Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

ObjectiveTo investigate the value of MELD 3.0， MELD， and MELD-Na scores in assessing the 90-day prognosis of patients with acute-on-chronic liver failure （ACLF） through a comparative study. MethodsA retrospective analysis was performed for the clinical data of 605 patients with ACLF who were treated in Tianjin Third Central Hospital， The Fifth Medical Center of Chinese PLA General Hospital， and Beijing YouAn Hospital from November 2012 to June 2019， and according to the 90-day follow-up results after admission， they were divided into survival group with 392 patients and death group with 213 patients. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， net reclassification improvement （NRI）， integrated discrimination improvement （IDI）， and decision curve analysis （DCA） curve were used to investigate the value of MELD 3.0， MELD， and MELD-Na scores at baseline， day 3， week 1， and week 2 in predicting the prognosis of the disease. ResultsAt day 3 and week 1， MELD 3.0 score had an AUC of 0.775 and 0.808， respectively， with a better AUC than MELD score （P<0.05）. At day 3， week 1， and week 2， MELD 3.0 score showed an NRI of 0.125， 0.100， and 0.081， respectively， compared with MELD in predicting the prognosis of ACLF patients， as well as an NRI of 0.093， 0.140， and 0.204， respectively， compared with MELD-Na score in predicting prognosis. At baseline， day 3， week 1， and week 2， MELD 3.0 showed an IDI of 0.011， 0.025， 0.017， and 0.013， respectively， compared with MELD in predicting the prognosis of ACLF patients. At day 3 and week 2， MELD 3.0 showed an IDI of 0.027 and 0.038， respectively， compared with MELD-Na in predicting the prognosis of ACLF patients. All the above NRIs and IDIs were >0， indicating a positive improvement （all P<0.05）. DCA curves showed that MELD 3.0 was superior to MELD at day 3 and was significantly superior to MELD-Na at week 2. There was no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with different types， and there was also no significant difference in the ability of the three scores in predicting the prognosis of ACLF patients with the etiology of HBV infection， alcohol， or HBV infection combined with alcohol， while MELD 3.0 was superior to MELD for ACLF patients with other etiologies （P<0.05）. ConclusionMELD 3.0 score is better than MELD and MELD-Na scores in predicting the 90-day survival of patients with ACLF， but with limited superiority.

Objective:Tumor-treating fields (TTFields) is a kind of non-invasive anti-mitotic tumor therapy, which has been approved for patients with newly diagnosed and recurrent glioblastoma. This study aims to explore the efficacy and safety of TTFields in high-grade gliomas in clinical practice settings.Methods:The clinical data of 15 patients with recurrent glioma and 9 patients with newly diagnosed high-grade glioma admitted to our center from April 2019 to January 2021 were retrospectively analyzed. All patients accepted TTFields≥1 month. Follow-up was performed for 5.3 months (ranged from 2.3 to 10.7 months); Response Assessment in Neuro-Oncology Working Group (RANO) criteria was used to evaluate the glioma responses. The progression-free survival (PFS) and overall survival (OS) were calculated according to Kaplan-Meier method. Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Quality of life questionnaire-core 30 (QLQ-C30) and QLQ-brain cancer module (QLQ-BN20) questionnaires were used to evaluate the health-related quality of life (HRQoL). Treatment compliance was evaluated by data on the use of NovoTTF-200A devices, and calculated as a percentage of daily TTFields usage.Results:The median duration of TTFields was 4.2 months (ranged from 1.0 to 10.7 months), with a median compliance rate of 91.5% (67.0%-97.0%). TTFields was used alone in 2 patients and used with combination of chemotherapy in 22 patients. From follow-up to April 2021, 14 patients had stable symptoms and 10 had disease progression (8 died). The median PFS and OS of recurrent patients were 5.9 months ( 95%CI: 3.3-8.6 months) and 8.5 months ( 95%CI: 3.2-13.8 months), respectively; and the median PFS and OS of newly diagnosed patients were both 10.7 months (without 95%CI). The common adverse events included grading 1 dAE (58.3%) and grading 2 dAE (12.5%), without grading 3 or 4 dAE, manifested as contact or allergic dermatitis, erosion, folliculitis and ulcers. And 87.5% patients had stable HRQoL. Conclusions:The preliminary results showed that the survival of recurrent high-grade glioma patients treated by TTFields is similar to that reported in foreign literature; and the newly diagnosed patients need further survival follow-up. The patients' treatment compliance and safety are good. The dAE incidence (grading 1-2) is higher than that reported in the literature, and the toxicity was acceptable.

Objective To investigate the effect of cisternostomy on the prognosis of patients with traumatic brain injury (TBI).Methods A retrospective case control study was conducted to analyze the clinical data of 46 patients with TBI admitted to Shanxi Dayi Hospital from May 2017 to September 2018.There were 37 males and nine females,aged 24-80 years [(49.8 ± 15.7)years].The injury severity score (ISS) was 6-42 points [(25.0 ± 8.2)points],and the Glasgow Coma score (GCS) was 3-14 points [(3.4 ± 1.7) points].Twenty-three patients underwent routine surgery only (control group),and 23 patients underwent cisternostomy (cisternostomy group) on the basis of routine surgery.Intracranial pressure monitoring was performed in both groups before surgery.The postoperative intracranial pressure,intracranial pressure 1 week after operation,postoperative mechanical ventilation time,neurosurgical ICU (NICU) time,postoperative dehydration dose,decompressive craniectomy rate,postoperative infection rate,mortality rate,length of hospital stay,GCS at discharge,and Glasgow outcome score (GOS) of 3 months of follow-up were compared between the two groups.Results Compared with the control group,the cistemostomy group had lower postoperative intracranial pressure [(7.1 ± 5.7) mmHg vs.(14.2 ± 12.0) mmHg)],intracranial pressure 1 week after operation [(11.8 ± 0.5) mmHg vs.(14.0 ± 0.7) mmHg],postoperative dosage of dehydrating agent [0 (0-500.0) ml vs.1 275 (787.5-3 812.5) ml] and decompression rate (57％ ∶ 91％) (P ＜ 0.05).There were no significant differences between the cistemostomy group and control group in postoperative mechanical ventilation time [120 (42.0-225.0)hours vs.89(65.5-203.5)hours],NICU time [236(182.0-340.5)hoursvs.281 (114-400)hours],postoperative infection rate (4％ vs.0),mortality rate (13％ vs.39％) and hospital stay [32 (20.0-44.5) hours vs.25 (12.0-30.5)hours] (P ＞ 0.05).The cisternostomy group had higher GCS score at discharge than the control group [(10.7 ± 4.2) points vs.(7.9 ± 4.2) points] (P ＜ 0.05).After 3 months of follow-up,18 patients in the cisternostomy group showed good prognosis,better than that in the control group (11 patients) (P ＜ 0.05).Conclusion For TBI patients,cisternostomy can clear the blood cerebrospinal fluid,reduce harmful metabolic products in the brain,reduce intracranial pressure and hence improve the prognosis of patients.

General Policies of Nomenclature for Biological Products in China were studied,aimed at establishing and perfecting the system of Chinese approved biologic name.By means of analysis of the current situation and existing problems of nomenclature for biological products and the development trend of new biotherapeutics.It is sufficiently studied on the existing leading international drug generic naming system,and the specific suggestions on revision of the General Policies of Nomenclature for Biological Products in China based on the naming principles of WHO INN and Chinese language recognition were put forward.

Objective To investigate the relationship between the composition of vaginal microbiota and the course of cervical precancerous lesion.Methods A total of 64 vaginal swabs were collected from 22 healthy women, 18 CINⅠ patients and 24 CINⅡ/Ⅲ patients who visited Obstetrics and Gynecology of the Second Xiangya Hospital of Central South University during July 2014 and July 2015.The Bacterial genomic DNA was extracted and the V3 and V4 hypervariable regions of 16S rRNA were amplified and high-throughput sequenced.The abundance and composition of vaginal microbiota were analyzed by Uparse, Mothur and LefSe statistical software.Results There was no significant difference in Alpha diversity index between CINⅡ/Ⅲ group(Chao:63±32;ACE:72±38;Simpson:0.70±0.27;Shannon:0.70±0.63) and control group ( Chao:48±24;ACE:54±25;Simpson:0.71±0.27;Shannon:0.65±0.58)(W=192,P=0.11;W=189,P=0.10;W=281,P=0.72;W=241,P=0.62).The ACE(85±37) and Chao(66±25) values of CINⅠgroup were significantly different from those of the control group (ACE:54±25;Chao:48±24)(W=99,P=0.006;W=113,P=0.02).At the phylum level, 78.69%(309 020/392 722) of the vaginal microbiota in the control group was Firmicutes, 16%(62 846/392 722) was Actinobacteria.Firmicutes was reduced to 64.86%(208 422/321 318) and Actinobacteria increased to 27.71%(89 040/321 318) in CINⅠgroup.The composition of vaginal microbiotain in CINⅡ/Ⅲ group was similar to those of control group.At the genus level, the composition of vaginal microbiota were similar between CINⅡ/Ⅲ group and control group, with Lactobacillus as predominant genus[71.81%(307 658/418 424)], Gardnerella[12.91%(55 299/428 424)], others such as Prevotella, atopobium were less.In the CINⅠ group, the abundance of Lactobacillus was decreased to 56.26%(180 787/321 318), Gardnerella was increased to 19.62%(63 057/321 318), and Listeria was increased to 7.7%(24 746/321 318).The composition of vaginal microbiota in the most samples was classified as CSTⅢ and CSTⅠ, with Lactobacillus inersand and Lactobacillus crispatus were dominant respectively.There was no significant difference in the composition of vaginal microbiota between the three groups(χ2=2.72, P=0.949).LEfSe analysis showed that the abundance of bacteria in CIN group and control group were varied.At the genus level, there were significant differences in the abundance of Geobacter, Atopobium and Ureaplasma (P<0.05, P<0.05, P<0.01, respectively).At the species level, there was significant difference in the abundance of Ureaplasma urealyticum serotype 9 (P<0.01).Conclusion The diversity and the composition of vaginal microbiota were similar between CIN patients and healthy women, but the abundances of some bacteria were varied, with Ureaplasma increased in patients with CIN.

OBJECTIVE:To explore the effectiveness and safety of pranoprofen combined with sodium hyaluronate in the treat-ment of moderate and severe dry eyes. METHODS:180 patients with moderate and severe dry eyes were divided into observation group and control group by random number table method,with 90 cases in each group. Control group was given Sodium hyaluro-nate eye drops,one drop each time,tid,and received physical therapy as cleaning eyelid,hot compress and glandulae tarsales mas-sage. Observation group was additionally given Pranoprofen eye drops,one drop each time,tid. A treatment course lasted for 2 weeks. The monocular corneal fluorescence staining score,break-up time of tear film(BUT),dry eye symptom scores,ShirmerⅠtest (SIT) before and after treatment,clinical efficacy and ADR were compared between 2 groups. RESULTS:2,4 weeks after treatment,monocular corneal fluorescence staining scores and dry eye symptom scores of 2 groups were significantly lower than be-fore treatment;BUT and SIT were significantly longer than before;those indexes after 4 weeks of treatment were significantly bet-ter than after 2 weeks of treatment;those indexes of observation group after 2,4 weeks of treatment were significantly better than those of control group at the same time,with statistical significance (P<0.05). The total effective rate of observation group was 94.44%,which was significantly higher than that of control group(78.89%),with statistical significance(P<0.05). Both groups suffered from eye irritation symptom to different extent,and no other severe complications was found. There was no statistical sig-nificance in eye irritation symptom score between 2 groups(P>0.05). CONCLUSIONS:For moderate and severe dry eyes,prano-profen combined with sodium hyaluronate can effectively control ocular inflammation and improve tear film stability. It shows defi-nite therapeutic efficacy and good safety.

OBJECTIVETo investigate the protective mechanism of endoplasmic reticulum stress (ERS) inhibition against inflammation-induced acute liver injury using a mouse model.

METHODSMarrow-derived stem cells were isolated from mouse femur and used to derive macrophages for analysis in experimental inflammation conditions, established by exposure to LPS and consequent activation of TLR4. Tunicamycin, an ERS chemical inducer, was applied to interfere the inflammation model condition.Affect on the inflammation-related factor MAPK was detected by western blot, and affects on gene expression of inflammatory factors were measured by real-time quantitative PCR. Affect on TNFa was also measured by ELISA.

RESULTSExpression of TNFa, IL-6 and IL-1b was induced upon exposure to LPS, with the peak levels being reached at 4 hours of exposure (TNFa, 0.82+/-0.24; IL-1 b, 2.20+/-0.69; IL-6, 0.330+/-0.150). Tunicamycin significantly enhanced the LPS-induced up-regulation of TNFa, IL-6 and IL-1b expression (TNFa, 1.44+/-0.38, t=2.8, P<0.05; IL-1b, 16.063.40, t =7.93, P<0.05; IL-6, 31.1610.60, t=5.08, P<0.05). The tuniamycin treatment also enhanced the LPS-induced up-regulation of the protein expression of phospo-p38, phospho-JNK and phoshpo-ERK.

CONCLUSIONERS collaborates with LPS to promote the TLR4-mediated inflammatory response of macrophages, and this collaboration may be a pathogenic mechanism underlying progressive development of acute liver injury.

Animals ; Disease Models, Animal ; Endoplasmic Reticulum Stress ; Inflammation ; Interleukin-6 ; Lipopolysaccharides ; Liver ; Macrophages ; Mice ; Toll-Like Receptor 4 ; Up-Regulation

Objective To investigate the feasibility of diffusion-weighted(DWI) MRI on basis of the intravoxel incoherent motion (IVIM) in nasopharyngeal carcinoma (NPC),and the diagnostic value of pure molecular diffusion coefficient (D),perfusion-related diffusion coefficient (D *) and perfusion fraction (f) in first onset NPC.Methods From December 2011 to January 2013,40 consecutive patients (26 men,14 women; median age,52 years) with suspected NPC were examined on a 3.0 T MR scanner.DW imaging was performed by using a single-shot echo-planar sequence with 13 b-values (0,10,20,30,50,80,100,150,200,300,400,600,800 s/mm2).MR imaging was compared with endoscopy and biopsy for the detection of NPC.Mean interval time between MR imaging examination and subsequent nasopharyngeal biopsy was 3 days (range,0-11 days).The subjects were divided into 2 groups according to the pathological results,group A was subjects with NPC (17 men,9 women; median age,35) and group B was ones with nasopharyngeal chronic hyperplastic inflammation(NPH) (9 men,5 women; median age,35).The D,D * and f were measured and compared in patients with first onset NPC and nasopharyngeal hyperplasia (Mann-Whitney test).Results IVIM DWI was successful in 24/26 with NPC and 12/14 with NPH.D value was significantly lower in A group compared with B group [mean,(0.70 ± 0.13) ×10-3 mm2/s vs (0.78 ± 0.05) × 10-3 mm2/s ; U =2.05,P ＜ 0.05],as was f value [mean,(16.25 ±1.46) ％ vs (26.20 ± 3.90) ％ ; U =11.16,P ＜ 0.01].However,D* value was significantly higher in Agroupas compared with B group[mean,(161.8 ±23.56) × 10-3 mm2/s vs (55.28 ± 17.05) × 10-3 mm2/s; U =13.90,P ＜0.01].Conclusions IVIM DWI is a feasible technique for investigating first onset NPC and D value has a certain value in differentiating NPC and NPH.D* value has an important potential value in distinguishing benign and malignant NPC.

To explore the possibility and condition of differentiation of bone marrow mesenchymal cells (BMSCs) to neural cells in vitro, BMSCs from whole bone marrow of rats were cultured. The BMSCs of passage 3 were identified with immunocytochemical staining of CD44 ( + ), CD71 ( + )and CD45(-). There were type Ⅰ and type Ⅱ cells in BMSCs. Type Ⅰ BMSCs were spindleshaped and strong positive in immunocytochemical staining of CD44 and CD71, whereas flat and big type Ⅱ BMSCs were lightly stained. The BMSCs of same passage were induced to differentiate into neural cells by β-mercaptoethanol (BME). After induction by BME, the type Ⅰ BMSCs withdrew to form neuron-like round soma and axon-like and dendrite-like processes, and were stained positively for neurofilament (NF). The type Ⅱ BMSCs did not change in the BME medium and were negatively or slightly stained of NF.