Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Vascular endothelial growth factor and its receptor play a very important regulatory role in the growth of liver tumors.In this paper,the pharmacological effects of artesunate nanoliposomes,the mecha-nism of artesunate nanoliposomes inhibiting tumor angiogenesis of liver cancer and the new targets of anti-cancer effects of drugs were discussed in order to provide new strategies for the treatment of liver cancer.

Objective To investigate the application effect of external treatment method of Xingqi Huoxue Zhitong Paste in the treatment of phlebitis. Methods Using mannitol as an inflammatory agent, a phlebitis model was established by infusion into the ear marginal vein of rabbits. Successfully modeled rabbits were randomly divided into four subgroups for intervention, while the blank control group was routinely raised without any intervention. After the intervention, the improvement effect of Xingqi Huoxue Zhitong Paste on mannitol-induced transfusion-induced phlebitis in rabbits was explored by observing the manifestations of phlebitis, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor A (VEGF-A) levels. Results The success rate was up to 90.0%. On the first day of treatment, there were 8 ineffective cases and 1 effective case in the saline group; 6 ineffective cases and 3 effective cases in the hirudoid group; 7 ineffective cases and 2 effective cases in the magnesium sulfate group; 7 ineffective cases and 2 effective cases in the Xingqi Huoxue Zhitong Paste group. There was no significant difference in the curative effect among the four groups (P=0.431). On the fourth day of treatment, there were 5 ineffective cases, 2 effective cases, and 2 markedly effective cases in the saline group; 1 effective case, 5 markedly effective cases, and 3 cured cases in the hirudoid group; 2 effective cases, 5 markedly effective cases, and 2 cured cases in the magnesium sulfate group; 2 effective cases, 4 markedly effective cases, and 3 cured cases in the Xingqi Huoxue Zhitong Paste group. On the fourth day of treatment, compared with the saline group, the curative effects of the hirudoid group (P=0.001), the magnesium sulfate group (P=0.020), and the Xingqi Huoxue Zhitong Paste group (P=0.003) were statistically significant. There was no significant difference in curative effect in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group when compared with the hirudoid group (P>0.05); there was no significant difference in curative effect in the Hirudoid group and the Xingqi Huoxue Zhitong Paste group when compared with the magnesium sulfate group (P>0.05); there was no significant difference in curative effect in the hirudoid group and the magnesium sulfate group when compared with the Xingqi Huoxue Zhitong Paste group (P>0.05). The effective rate of the saline group was 11.1%, and the cure rate was 0%. The effective rate of the hirudoid group was 100.0%, and the cure rate was 33.3%. The effective rate of the magnesium sulfate group was 77.7%, and the cure rate was 44.4%. The effective rate of the Xingqi Huoxue Zhitong Paste group was 66.7%, and the cure rate was 22.2%. The drug effectiveness of the Xingqi Huoxue Zhitong Paste group, the hirudoid group, and the magnesium sulfate group was higher than that of the saline group (P < 0.05). After the intervention, the levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the four model subgroups were statistically significant compared with the blank control group (P < 0.05). The levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the saline group showed significant difference from those in the hirudoid group, the magnesium sulfate group, and the Xingqi Huoxue Zhitong Paste group (P < 0.05). Compared with the hirudoid group, the differences in serum inflammatory factors IL-6, TNF-α, and VEGF-A contents in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group were statistically significant (P < 0.05). The inflammatory factor levels in the blank control group were the lowest, while those in the normal saline group were the highest. Conclusion Xingqi Huoxue Zhitong Paste group has an improving effect on mannitol-induced infusion phlebitis in rabbits, but its efficacy is inferior to that of the commonly used hirudoid ointment. Therefore, appropriate adjustments and improvements can be made to the drug formula to enhance its effectiveness.

INTRODUCTION: The purpose of this study was to assess the application of the early warning score system (EWS-S) and gauge physician awareness, perceptions of necessity and attitudes regarding these tools based on previously experienced unnoticed clinical deterioration (CDET). METHODS: A cross-sectional survey was carried out via an online questionnaire at a large 3,500-bed Class 3A general hospital in China. A total of 299 physicians of adult general wards were asked to answer a translated questionnaire that was localised from the original version. Demographic profiles of patients were included as well as three other sections assessing awareness of CDET/EWS-S and gauging attitudes towards and perceptions of the necessity of EWS-S at our hospital. RESULTS: A high level of physician awareness of the CDET problem was observed. Most physicians knew about the existence of a systematic assessment tool for clinical application. Physicians with previous experience in reanimation, unplanned transfer to intensive care unit (UTICU) and/or death tended to consider EWS-S necessary in attentive and well-trained staff (p < 0.05). Physicians who had previous experience with UTICU were more likely to recommend implementing EWS-S in their wards compared with those without such experience (p < 0.05). CONCLUSION Most physicians have positive attitudes towards EWS-S. However, their awareness should be further heightened. Physicians who had previous experience with CDET/UTICU were more likely to employ EWS-S in their clinical practices. To better facilitate the implementation of EWS-S in Chinese hospitals, existing facilities, policy supports, standardised managements and the development of information systems should be strengthened.
Adult ; Attitude ; Clinical Deterioration ; Cross-Sectional Studies ; Early Warning Score ; Humans ; Physicians

Objective:To explore the predictive value of the modified NUTrition risk in the critically ill (mNUTRIC) score for chronic critical illness (CCI) in elderly sepsis patients.Methods:A prospective observational study was conducted. Elderly sepsis patients admitted to Medical Intensive Care Unit (MICU) of General Hospital of Southern Theatre Command for more than 24 h from August 2019 to January 2021 were enrolled. Age, sex, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, acute gastrointestinal injury (AGI) score, clinical frailty score and mNUTRIC score at admission, length of ICU stay, usage of mechanical ventilation and renal replacement therapy were recorded. According to the occurrence of CCI, patients were divided into the CCI group and rapid recovery (RAP) group, and the differences between the two groups were compared. The risk factor of CCI after sepsis in elderly patients were analyzed by log-binomial regression analysis. Receiver operating characteristic (ROC) analysis was performed for mNUTRIC score. Differences were considered significant at P<0.05. Results:Of the enrolled 91 sepsis patients, 14 (15%) patients died within the first week, 37 (41%) exhibited RAP and 40 (44%) developed CCI. The CCI patients were significantly older and presented a higher APACHE Ⅱ score, CFS score, mNUTRIC score, and usage of mechanical ventilation and renal replacement therapy compared with the RAP patients ( P<0.05). Multivariate regression analysis revealed that mNUTRIC score was an independent risk factor for the development of CCI in elderly sepsis patients, prevalence ratio was 1.503 (95% CI: 1.007-2.244). The area under the curve (AUC) of mNUTRIC score was 0.706 (95% CI: 0.592-0.805). Conclusions:The mNUTRIC score at the time of admission in the intensive care unit can be used to predict CCI after sepsis in elderly sepsis patients.

Objective:To establish a 180-day mortality predictive score based on frailty syndrome in elderly sepsis patients [elderly sepsis score (ESS)].Methods:A prospective study for sepsis patients aged 60 years and above who were admitted to a medical intensive care unit of the General Hospital of Southern Theatre Command from January 1st, 2018 to December 31st, 2018 was conducted. Univariate analysis was performed on 19 independent variables including gender, age, body mass index (BMI), tumor, charlson comorbidity index (CCI), activity of daily living (ADL), instrumental activity of daily living (IADL), mini-mental state examination (MMSE), geriatric depression scale (GDS), clinical frail scale (CFS), sequential organ failure assessment (SOFA), Glasgow coma scale (GCS), acute physiology and chronic health evaluation (APACHEⅡ, APACHEⅣ), modified NUTRIC score (MNS), multiple drug resistance (MDR), mechanical ventilation (MV), continuous renal replacement therapy (CRRT) and palliative care. Continuous independent variables were converted into classified variables. Multivariate binary regression analysis of risk factors was conducted to screen independent risk factors which affecting 180-day mortality in elderly sepsis patients. Then a 180-day mortality predictive score was established, and the discrimination of the mortality of patients using CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS scores were compared.Results:A total of 257 patients were enrolled, with a 180-day mortality of 60.7%. Univariate analysis showed that age, tumor, CCI, ADL, IADL, MMSE, CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ, MNS, MDR, MV, CRRT, palliative care were risk factors of 180-day mortality in elderly sepsis patients [age: odds ratio ( OR) = 1.027, 95% confidence interval (95% CI) was 1.005-1.050, P = 0.018; tumor: OR =2.001, 95% CI was 1.022-3.920, P = 0.043; CCI: OR = 1.193, 95% CI was 1.064-1.339, P = 0.003; ADL: OR = 0.851, 95% CI was 0.772-0.940, P = 0.001; IADL: OR = 0.894, 95% CI was 0.826-0.967, P = 0.005; MMSE: OR = 0.962, 95% CI was 0.937-0.988, P = 0.004; CFS: OR = 1.303, 95% CI was 1.089-1.558, P = 0.004; SOFA: OR = 1.112, 95% CI was 1.038-1.191, P = 0.003; GCS: OR = 0.918, 95% CI was 0.863-0.977, P = 0.007; APACHEⅡ: OR = 1.098, 95% CI was 1.053-1.145, P < 0.001; APACHEⅣ: OR = 1.032, 95% CI was 1.020-1.044, P < 0.001; MNS: OR = 1.315, 95% CI was 1.159-1.493, P < 0.001; MDR: OR = 2.029, 95% CI was 1.197-3.437, P = 0.009; MV: OR = 6.408, 95% CI was 3.480-11.798, P < 0.001, CRRT: OR = 2.744, 95% CI was 1.529-4.923, P = 0.001, palliative care: OR = 5.760, 95% CI was 2.177-15.245, P < 0.001]. By binary regression analysis, CFS stratification ( OR = 1.934, 95% CI was 1.267-2.953, P = 0.002), MV ( OR = 4.531, 95% CI was 2.376-8.644, P < 0.001), CRRT ( OR = 2.471, 95% CI was 1.285-4.752, P = 0.007), palliative care ( OR = 6.169, 95% CI was 2.173-17.515, P = 0.001) were independent risk factors of 180-day mortality in elderly patients with sepsis. The model of "ESS = 0.660×CFS stratification+1.511×MV+0.905×CRRT+1.820×palliative care" was established. Receiver operating characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) for predicting 180-day mortality by ESS was 0.785 (95% CI was 0.730-0.834, P < 0.001). When the best cut-off value was 2.2 points, its sensitivity was 78.9%, specificity was 70.3%, the positive predictive value was 80.4%, and the negative predictive value was 68.3%. Simplified ESS was defined as "0.5×CFS stratification+1.5×MV+1×CRRT+2×palliative care". ROC curve analysis showed that AUC for predicting 180-day mortality by simplified ESS was 0.784 (95% CI was 0.729-0.833, P < 0.001). When the best cut-off value was 2.0 points, sensitivity was 76.9%, specificity was 70.3%, the positive predictive value was 80.0%, and the negative predictive value was 66.4%. Compared with CFS, SOFA, GCS, APACHEⅡ, APACHEⅣ and MNS, ESS had a significant difference in discriminating 180-day mortality in elderly patients with sepsis (AUC was 0.785 vs. 0.607, 0.607, 0.600, 0.664, 0.702, 0.657, 95% CI: 0.730-0.734 vs. 0.537-0.678, 0.537-0.677, 0.529-0.671, 0.598-0.730, 0.638-0.766, 0.590-0.725, all P < 0.05). Conclusions:CFS, MV, CRRT, and palliative care are independent risk factors of 180-day mortality in elderly patients with sepsis. We established ESS based on these risk factors. The ESS model has good discrimination and can be used as a reference and assessment tool for prediction and treatment guidance in elderly patients with sepsis.

Objective:To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B.Methods:Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data, and Spearman’s rank-correlation test was used for rank correlation analysis. Results:There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues ( χ2MH = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade ( rs = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis ( χ2MH = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage ( rs = -0.713, P < 0.05). Conclusion:HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective To investigate the regulation effect of emodin on human embryonic liver L02 cells strain farnesoid X receptor (FXR) pathways.Methods By using Guggulsterones,FXR genes were intervened with in L02 cells as model group,in three different concentrations of emodin (50.0 μ mol/L,25.0 μmol/L,12.5 μmol/L) of emodin in the model group cells,FXR,small heterodimer parter (SHP),UDP-glucuronosyltransferase 2B4 (UGT2 B4),bile salt export pump(BSEP) mRNA and protein expressions were detected by real-time fluorescent quantitative PCR and Western blot test.Results (1) The relative expressions of FXR mRNA and protein in the model group (0.240 ± 0.021,0.385 ±0.119) decreased significantly than those of control group (1.000 ± 0.088,1.000 ± 0.223),the differences were statistically significant (t =14.62,4.21,all P ＜ 0.01).Compared with the model group,the relative expressions of FXR mRNA in the high,the middle and the low-dose emodin groups (0.755 ±0.083,0.817 ±0.097,0.547 ± 0.080) were significantly higher (t =10.42,10.03,6.39,all P ＜ 0.01).The relative expressions of FXR protein in the medium-dose group (0.865 ± 0.203) increased significantly (t =3.53,P ＜ 0.01).The relative expressions of FXR mRNA in the high and the medium-dose groups (0.755 ± 0.083,0.817 ± 0.097) were higher than those in the low-dose group (0.547 ± 0.080),the differences were statistically significant (t =3.11,3.70,all P ＜ 0.01).(2)The relative expressions of SHP,UGT2B4,BSEP mRNA and protein in the model group (0.148 ±0.025,0.205 ± 0.039,0.184 ± 0.020;0.458 ± 0.130,0.255 ± 0.170,0.303 ± 0.100) were significantly lower than those in the control group (1.000 ±.0.099,1.000 ±0.104,1.000 ±0.125;1.000 ±0.129,1.000 ±0.157,1.000 ±0.162),the differences were statistically significant (t =14.50,12.44,11.19,5.13,5.57,6.33,all P ＜ 0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high,the middle and the low-dose groups (0.610 ± 0.058,0.514 ± 0.041,0.707 ± 0.062;0.755 ± 0.108,0.800 ± 0.086,0.727 ± 0.076;0.470 ± 0.070,0.582 ± 0.050,0.500±0.108) were significantly lower than those in the model group (0.148 ± 0.025,0.205 ± 0.039,0.184 ± 0.020),the differences were statistically significant (t =12.75,9.38,13.94,9.46,10.90,11.96,7.53,10.31,5.00,all P ＜0.01).The relative expressions of SHP,UGT2B4 and BSEP mRNA in the high and the middle-dose emodin group (0.658 ±0.091,0.624 ±0.113,0.607 ±0.097;0.868 ±0.194,0.883 ±0.099,0.913 ±0.131) were significantly higher than those in the low-dose group (0.458 ±0.130,0.255 ±0.170,0.303 ±0.100),the differences were statistically significant (t =2.18,3.13,3.78,3.05,5.53,6.41,all P ＜ 0.01).The relative expression of SHP and BSEP protein in the low-dose group (0.645 ±0.135,0.572 ±0.076) increased,the differences were statistically significant (t =1.73,P ＜ 0.05,t =3.72,P ＜ 0.01).The relative expression of BSEP protein in the high and the medium-dose groups (0.607 ±0.097,0.913 ± 0.131) was significantly higher than those in the low-dose group (0.572 ± 0.076),the differences were statistically significant (t =1.99,3.90,all P ＜ 0.01).The relative expressions of SHP and UGT2B4 mRNA in the high and the low-dose group (0.610 ±0.058,0.470 ±0.070;0.514 ± 0.041,0.582 ± 0.050) were significantly lower than those in the medium-dose group (0.800 ± 0.086),the differences were statistically significant (t =3.75,6.47,3.83,3.42,all P ＜ 0.01).The expression levels of UGT2B4 and BSEP in the high and the low-dose groups (0.624 ± 0.113,0.644 ± 0.097;0.607 ± 0.097,0.572 ± 0.076) were significantly lower than those in the medium-dose group (0.883 ± 0.099,0.913 ± 0.131),the differences were statistically significant (t =4.27,2.98,6.30,3.90,all P ＜ 0.01).Conclusions Guggulsterones can inhibit FXR and downstream genes SHP,UGT2B4,BSEP expressions in L02,and emodin can enhance FXR gene expression,promote SHP,UGT2B4,BSEP gene expression,inhibit cholestasis pathway,protection of liver cell,which shows a dosage discreapancy.