Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9％NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P＜0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.

Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.

Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P＜0.05,P＜0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P＞0.05),but the other indexes in CORT group were statistically significant(all P＜0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q_1,Q₃) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.
Adult ; Alphapapillomavirus ; Case-Control Studies ; Cervical Intraepithelial Neoplasia ; Erythrocytes ; Female ; Folic Acid ; Humans ; Male ; Middle Aged ; Papillomaviridae ; Papillomavirus Infections ; Uterine Cervical Neoplasms

Objective: To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥2 (CIN2+). Methods: The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27^th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results: A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI: 0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI: 1.92-7.99), 10.50 (95%CI: 3.67-30.04) and 3.65 (95%CI: 1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI: 1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI: 1.03-2.98). Conclusion: The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.
Female ; Humans ; Methylation ; Human papillomavirus 16/genetics* ; Asian People ; Uterine Cervical Neoplasms ; Uterine Cervical Dysplasia

Metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was used to study the initiation and development of diabetes in rats, and the ability of Ginkgo biloba extract (GBE) to ameliorate this pathology. Diabetes mellitus (DM) was induced by intra-peritoneal injection of streptozotocin. The rats were randomly divided into a normal control group treated with drug-free solution (NC), a normal control group treated with GBE (N-GBE), a DM group treated with drug-free solution (DM), and a DM group treated with GBE (D-GBE); rats were maintained on this protocol for 9 weeks. Rat plasma was collected from the sixth week to the ninth week and then analyzed with LC-MS. Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Xuzhou Medical University. Twelve plasma metabolites with continuous differentiation were monitored to indicate dysfunction of metabolic pathways including fatty acid metabolism, phospholipid metabolism, amino acid metabolism, tricarboxylic acid cycle activity, bile acid metabolism, and purine metabolism to confirm the occurrence and development of DM. Treatment with GBE partially reversed the changes seen in five metabolites in DM rats, indicating that GBE could prevent the occurrence and development of DM by acting on fatty acid metabolism, phospholipid metabolism, amino acid metabolism, and the tricarboxylic acid cycle.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective:To investigate the promoting effect of Ginsenoside Ro on the differentiation of THP-1-derived dendritic cells (DCs) induced by GM-CSF and IL-4.Methods: Sensitive leukemia-derived DC cell line was screened first.Then,the selected sensitive cell line THP-1 was stimulated to differentiate into DCs by cytokines (GM-CSF and IL-4) and small(5 μmol/L),middle(10 μmol/L),and large (20 μmol/L) dose of Ginsenoside Ro respectively.The expressions of CD1a,MHCⅡ and CD86 of leukemia-derived DCs were detected by flow cytometry.In addition,the transcription levels of CD1a,CD86 and MHCⅡ of leukemia-derived DCs were detected by RT-PCR.ELISA was used to measure the protein levels of TNF-α and IL-6 in the culture supernatant.Results: THP-1 was the sensitive leukemia cell line which could be induced to differentiate into DCs by cytokines.Compared with cytokine stimulation alone,the expression of CD1a,MHCⅡ and CD86 in leukemia-derived cells was significantly increased after the stimulation of Ginsenoside Ro combined with cytokine(P<0.05).The CD1a,CD86 and MHCⅡ mRNA expression was significantly increased after the treatment of Ginsenoside Ro combined with cytokine(P<0.05).Moreover,the protein levels of TNF-α and IL-6 in culture supernatant were significantly increased (P<0.05) after the stimulation of Ginsenoside Ro in combination with cytokines.Conclusion: Ginsenoside Ro can significantly promote the differentiation of leukemia-derived DCs.