ObjectiveTo develop the Evidence Grading Scale for Ancient classical prescriptions in Traditional Chinese medicine， assess its reliability and validity， and apply it in practice to provide multi-source evidence for clinical practice guidelines development. MethodsLiterature retrieval was conducted to extract and screen existing evaluation dimensions， then the initial items were summarized using thematic analysis. Experts in the clinical medicine， medical history and literature participated in the Delphi questionnaire survey to evaluate and refine the items. An expert consensus meeting was conducted to finalize the included items， refine the method for items evaluation and evidence grading. The evidence quality rating scale for ancient classical traditional Chinese medicine （TCM） prescriptions was then established and tested for reliability and validity. ResultsThrough literature review， extraction， screening and summarization， a total of 3 dimensions and 12 initial items were formed. Questionnaires were sent to 69 experts to evaluate the initial items， with a questionnaire response rate of 100% and an expert authority coefficient of 0.92. All 12 items were retained for they had importance scores above 4. The Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine includes 3 dimensions with 12 items. The 3 dimensions includes ancient evidence， inheritance status， and modern application. Each dimension contains 4 items， and each item has a full score of 5 points. The evidence was rated as high-level， moderate-level， and low-level according to the final scores. The content validity index （CVI） of the 12 items was ＞0.9， the average CVI of the scale was 0.98， and the intraclass correlation coefficient （ICC） was 0.90. ConclusionThe Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine has good reliability and validity， which is practical for use in the development of TCM clinical guidelines and can better support clinical decision-making.

Objective:The differentially expressed genes(DEGs)and activated signaling pathways in systemic sclerosis(SSc)were screened by bioinformatics methods,and Chinese medicines for potential treatment of SSc were explored,providing a new theoretical basis for the study of SSc and the screening of potential markers.Methods:The data sets GSE58095,GSE130953,GSE33463 and GSE58613 were selected from GEO database and divided into skin group and peripheral blood group according to the sample source.The DEGs of SSc patients was analyzed by R language,and the Wayne diagram was drawn to take the intersection of the two groups.Metascape was used for GO enrichment analysis and KEGG pathway enrichment analysis,and STRING and Cytoscape were used for protein interaction network analysis to find key pathways and hub genes.The core genes were mapped to the medical on-tology information retrieval platform,and related Chinese medicines for SSc treatment were screened.The effective components of Chi-nese medicines were obtained through TCMSP and HERB databases,and the target letters of active ingredients were obtained through swiss database.The"drug-active ingredient-target"network was constructed by Cytoscape.Results:Total 218 DEGs were identified from the skin group of patients with SSc,and 283 DEGs were screened from peripheral blood of patients with SSc.Among them,there were 7 DEGs co-upregulated in skin and peripheral blood,namely ISG15,LGALS3BP,BST2,C1QB,IFI27,CEACAM1 and FBP1.CAMK2N1 was up-regulated in skin but down-regulated in peripheral blood,ARG1 was down-regulated in skin but up-regulated in pe-ripheral blood.GO and KEGG analysis of SSc DEGs showed that these genes were significantly enriched in inflammatory response,he-moglobin complex,immune receptor activity and extracellular matrix.The results of protein interaction network suggest that more than 10 genes such as COL1A1,CTGF12,IL1B,IFNG and JUN may be potential markers of SSc and core genes of therapeutic targets.The potential Chinese medicines screened for SSc treatment include ginseng,sanguisorba,convolvula,wolfberry,safflower,etc.The main components of these herbs were β-sitosterol,quercetin,kaempferol,stigmasterol,luteolin,sitosterol,Spinasterol,and the target were AKR1B1,AR,CYP1B1,XDH,etc.Conclusion:This study uses bioinformatics to screen out core genes that may be potential markers and therapeutic targets for SSc,which is expected to be a new target for the early diagnosis and mechanism research of SSc.Meanwhile,the mapped Chinese medicine and its effective components can provide ideas for the research and development of Chinese medicine compounds for the treatment of SSc.

Objective:The differentially expressed genes(DEGs)and activated signaling pathways in systemic sclerosis(SSc)were screened by bioinformatics methods,and Chinese medicines for potential treatment of SSc were explored,providing a new theoretical basis for the study of SSc and the screening of potential markers.Methods:The data sets GSE58095,GSE130953,GSE33463 and GSE58613 were selected from GEO database and divided into skin group and peripheral blood group according to the sample source.The DEGs of SSc patients was analyzed by R language,and the Wayne diagram was drawn to take the intersection of the two groups.Metascape was used for GO enrichment analysis and KEGG pathway enrichment analysis,and STRING and Cytoscape were used for protein interaction network analysis to find key pathways and hub genes.The core genes were mapped to the medical on-tology information retrieval platform,and related Chinese medicines for SSc treatment were screened.The effective components of Chi-nese medicines were obtained through TCMSP and HERB databases,and the target letters of active ingredients were obtained through swiss database.The"drug-active ingredient-target"network was constructed by Cytoscape.Results:Total 218 DEGs were identified from the skin group of patients with SSc,and 283 DEGs were screened from peripheral blood of patients with SSc.Among them,there were 7 DEGs co-upregulated in skin and peripheral blood,namely ISG15,LGALS3BP,BST2,C1QB,IFI27,CEACAM1 and FBP1.CAMK2N1 was up-regulated in skin but down-regulated in peripheral blood,ARG1 was down-regulated in skin but up-regulated in pe-ripheral blood.GO and KEGG analysis of SSc DEGs showed that these genes were significantly enriched in inflammatory response,he-moglobin complex,immune receptor activity and extracellular matrix.The results of protein interaction network suggest that more than 10 genes such as COL1A1,CTGF12,IL1B,IFNG and JUN may be potential markers of SSc and core genes of therapeutic targets.The potential Chinese medicines screened for SSc treatment include ginseng,sanguisorba,convolvula,wolfberry,safflower,etc.The main components of these herbs were β-sitosterol,quercetin,kaempferol,stigmasterol,luteolin,sitosterol,Spinasterol,and the target were AKR1B1,AR,CYP1B1,XDH,etc.Conclusion:This study uses bioinformatics to screen out core genes that may be potential markers and therapeutic targets for SSc,which is expected to be a new target for the early diagnosis and mechanism research of SSc.Meanwhile,the mapped Chinese medicine and its effective components can provide ideas for the research and development of Chinese medicine compounds for the treatment of SSc.

Purpose/Significance To explore the characteristics and clinical significance of differentially expressed genes closely re-lated to HPV E6/E7 by using bioinformatics.Method/Process The cervical tissue and clinical information of cervical cancer in TCGA and GTEx of UCSC are used as the training set.The expression profile chip GSE63514 related to cervical cancer in GEO is used as the validation set.Firstly,the limma package of R software is used to screen DEGs of tumor and normal samples,and Venn map of genes re-lated to E6/E7 protein in MigDB is made.Survival analysis is performed by survival kit and verified by ROC and protein expression lev-els.Secondly,key genes are obtained by copy number variation and methylation correlation.Finally,the specific co-expression network is constructed and enrichment analysis and immune infiltration analysis are performed.Result/Conclusion There are 101 differentially expressed genes related to HPV E6/E7 protein,and three genes are found to have significance after screening,namely E2F1,MCM4 and PCNA.At the same time,it is found that the genes in the specific coexpression network are significantly enriched in the DNA replication and chromosome organization pathways.Immune correlation analysis shows that key genes are significantly associated with CD4 T cells,B cells and neutrophils.DNA replication,chromosome organization,etc.,are the molecular mechanisms and key genes significantly related to the development of cervical squamous cell carcinoma and HPV E6/E7 encoded proteins.

Objective:To identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA by using bioinformatics analysis and explore the effects of DMARDs such as methotrexate, tocilizumab and rituximab on the DEGs in RA synovium.Methods:RA expression profile microarray data GSE7307、GSE12021、GSE55457、GSE55235、GSE77298、GSE89408 were acquired from the public gene chip database (GEO), including 113 synovial tissue samples from RA and 70 healthy controls (HC). At the same time, synovial expression microarrays GSE45867, GSE24742 and GSE97165 after DMARDs treatment were obtained. These data included 8 samples treated with methotrexate, 12 treated with tocilizumab, 12 treated with rituximab and 19 treated with combined tDMARDs. R software was used to screen DEGs and Venn plots using gene ontology function enrichment and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Hub genes were selected by STRING online analysis tool and Cytoscape software.Results:Compared with HC, 797 DEGs were up-regulated and 434 DEGs were down-regulated in the synovial tissue of RA. These DEGs were mainly enriched in T cell activation, immune response-activating cell surface receptor signaling pathway. Using Cytoscape and cytoHubba to obtain 5 sets of DEGs based on the STRING database model, the degree algorithm screened out 10 hub genes: LCK, SYK, PTPRC, HLA-DRA, LYN, NCAPG, TOP2A, JUN, CXCR4, CCNB1. Methotrexate treatment significantly up-regulated 20 DEGs and down-regulated 30 DEGs. Rituximab treatment up-regulated 100 DEGs and down-regulated 55 DEGs. Tocilizumab treatment up-regulated 91 DEGs and down-regulated 317 DEGs. These altered DEGs were enriched in regulating cell adhesion, leukocyte-cell adhesion, leukocyte transfer, and insulin-like growth factor receptor signaling pathways. It was worth noting that after treatment, a total of 306 high-expressing DEGs were down-regulated, and 36 low-expressing DEGs were up-regulated.Conclusion:LCK, insulin-like growth factor receptor signaling pathway, etc. are the responsible molecular mechanisms and key pivot genes for the occurrence and development of RA, and the treatment of DMARDs, which are closely related to the response of RA to the treatment of DMARDs.

Objective:To explore the characteristics of the changes in risk score for intensive care unit (ICU) patients during hospitalization by the intelligent calculation method, and to provide evidence for the risk prevention.Methods:In this retrospective study, ICU patients of the Fifth Central Hospital in Tianjin from November 3, 2021 to March 28, 2022 were enrolled and divided into ≥ 14 days group, 10-13 days group, 7-9 days group, and 3-6 days group according to the ICU length of stay. Risk scores assessed by the intelligent calculation method of the ICU patients were collected, including nutritional risk screening 2002 (NRS 2002), Caprini score and Padua score. NRS 2002 score for all patients, Caprini score for surgical patients and Padua score for internal medicine patients were selected. Trends in change of each score were compared between patients admitted to ICU 1, 3, 7 (if necessary), 10 (if necessary), and 14 days (if necessary).Results:A total of 138 patients were involved, including 79 males and 59 females, with an average age of (61.71±18.86) years and an average hospital stay of [6.00 (4.00, 9.25)] days. ① in the group with ICU length of stay ≥ 14 days (21 cases): there was no significant change in the NRS 2002 scores of the patients within 10 days, but the NRS 2002 score was significantly decreased in 14 days as compared with 1 day [3.00 (2.50, 3.50) vs. 4.00 (3.00, 5.00), P < 0.05]; both Caprini and Padua score were increased with prolonged hospital stay and compared with 1 day, the scores at the other time points were significantly increased, especially at 14 days [Caprini score: 5.00 (3.25, 7.00) vs. 2.50 (1.25, 5.50), Padua score: 6.00 (6.00, 7.00) vs. 3.00 (1.00, 3.00), both P < 0.05].② in the group with ICU length of stay from 10-13 days (15 cases): with the prolonged hospital stay, there was no significant change in NRS 2002 score, but both Caprini and Padua score were increased at 3, 7, 10 days, especially at 10 days [Caprini score: 3.00 (2.00, 4.75) vs. 2.00 (0.25, 2.75), Padua score: 5.00 (3.50, 6.00) vs. 2.00 (0.50, 4.00), both P < 0.05].③ in the group with ICU length of stay from 7-9 days (23 cases): compared with 1 day, the NRS 2002 score at 3 days and7 days were decreased, but the Caprini and Padua score were increased, especially at 7 days [NRS 2002 score: 2.00 (1.00, 4.00) vs. 2.00 (2.00, 4.00), Caprini score: 3.00 (2.00, 5.50) vs. 2.00 (0.25, 3.00), Padua score: 5.00 (4.00, 6.00) vs. 2.00 (0, 2.00), all P < 0.05]. ④ in the group with ICU length of stay from 3-6 days (79 cases): compared with 1 day, the NRS 2002 score at 3 days was decreased [NRS 2002 score: 2.00 (1.00, 3.00) vs. 2.00 (1.00, 3.00), P < 0.05], Caprini and Padua score were significantly increased [Caprini score: 3.00 (2.00, 4.00) vs. 2.00 (1.00, 3.00), Padua score: 5.00 (4.00, 5.00) vs. 2.00 (1.00, 3.00), both P < 0.05]. Conclusion:Based on dynamic assessment of intelligent calculation methods, the risk of thrombosis in ICU patients increased with hospital length of stay, and the nutritional risk was generally flat or reducing in different hospitalization periods.

Objective: To investigate the effect of erythropoietin (EPO) on the expression of aquaporin 2-3 after the release of unilateral ureter obstruction in young rats. Methods: Twenty-four SD rats were randomly divided into 3 groups(CUUO-R group, CUUO-R+ EPO group and sham group, with 8 rats in each group). The CUUO-R model was built through unilateral ureteral ligation, after 48 h the obstruction was released.EPO was given to the CUUO-R+ EPO group at the time point of removing obstruction, and then repeated every other day for 1 week, and the same volume of saline was simultaneously given to the CUUO-R rats.The rats in sham group experienced the laparotomy and free dissection of left ureter but not ligation.The kidneys were harvested 7 d after the release of CUUO.The methods of Western blot and immunohistochemistry were used to examine the effects of erythropoietin on the expression of AQP2 and AQP3. Results: The osmotic pressure of CUUO-R+ EPO group was higher than those of CUUO-R group, but lower than that of sham group(P=0.007). The concentration of creatinine and urea in the CUUO-R group[(58.001±2.416) μmol/L and (9.025±1.158) mmol/L]were higher than those of CUUO-R+ EPO group [(57.072±2.286) μmol/L and (1.479±0.043) mmol/L] and sham group [(54.820±1.536) μmol/L and (6.929±0.604) mmol/L]. The differences of the concentration of creatinine and urea between CUUO-R group and sham group were statistically significant(P<0.05). There was no significant difference between CUUO-R+ EPO group and Sham group(P>0.05). The immunohistochemistry showed that the expressions of AQP2 and AQP3 in co-llecting duct in CUUO-R group were significantly weaker than those of in sham group, and the expression of those in CUUO-R+ EPO group were slightly weaker than sham group.These results were further confirmed by Western blot, as the relative quantity of AQP2 and AQP3 were also the lowest in CUUO-R group(AQP2 in 3 groups were 0.974±0.109, 1.923±0.097 and 2.002±0.044, F=392.4, P=0.000; AQP3 in 3 groups were 0.941±0.048, 1.497±0.043 and 1.863±0.043, F=735.8, P=0.000). Conclusions EPO treatment is beneficial for the recovery expre-ssion of AQP2 and AQP3 as well as renal function at the early period after the release of ureteral obstruction in young rats.

Objective To explore the monitoring of cerebrospinal fluid (CSF) dynamics in a model of brain herniation induced by acute intracranial hypertension in Guangxi Bama-Mini pigs by phasecontrast cine magnetic resonance imaging (PC cine MRI).Methods Femoral artery blood were extracted from 10 pigs,and injected into the frontal and temporal parietal lobe to make a model of brain herniation induced by acute intracranial hypertension.The mean arterial blood pressure (MAP),intracranial pressure (ICP),and cerebral perfusion pressure (CPP) were monitored.Routine T1WI,T2WI,coronal,sagittal and cerebrospinal fluid flow sequence (fast PC cine slice) which positioned on the cervical 3 (C3) vertebral body as the center and perpendicular to the spinal scans were performed on all experimental animals before and after blood injection with 3.0T Magnetic Resonance Imaging.The ICP,MAP,CPP,the absolute values of CSF peak flow velocity and the absolute value of carotid peak flow velocity before and after blood injection were compared.Results The ICP,MAP,CPP,and the absolute value of CSF peak flow velocity before injection of autologous arterial blood were statistically significant as compared with those after blood injection [(6.80±2.044) mmHg vs (52.20±1.619) mmHg,(76.80±7.068) mmHg vs (142.80±12.399) mmHg,(70.00±6.074) mmHg vs (90.50±12.250) mmHg,and the absolute value of CSF peak flow velocity was (243.20±77.671) mm/s vs (201.40±55.482) mm/s,respectively,P＜0.01].The absolute value of the peak velocity of the carotid artery before blood injection was not statistically significant compared with that after blood injection [(876.80±239.908) mm/s vs (799.40±241.829) mm/s,P＞0.05].Conclusion After the formation of brain herniation induced by acute intracranial hypertension,the CSF flow in the C3 level spinal canal showed a low dynamic change,and the CSF flow velocity waveform was disordered and malformed.The non-invasive measurement of CSF dynamics by PC cine MRI can provide an important basis for the change of CSF dynamics in the model of brain herniation induced by acute intracranial hypertension,and provide a theoretical basis for further research on damage control neurosurgery in the future.

Objective To indentify the cognitive status of Chinese patients to acne and the influencing factors to theirs' cognitive status,so as to provide solid evidences for the prevention and treatment of acne.Methods A self-designed questionnaire was made to conduct this survey of 16,156 acne patients,who seeked to the treatment in the dermatological departments from 112 hospitals in China.The survey consisted of several parts,including the general status of patients,the patients' cognition of occurrence,development and risk factors of acne,whether the first choice was seeking treatment at the hospital when the patients had acne and the condition of selection of skin care products.The factors were analyzed,which could impact the cognition of the patients' behavior of treatment,how did the patients' cognition to influence their medical behavior and skin care as well as the consistency of assessment of the severity of acne by doctors and patients themselves.Results The acne patients studied had the best knowledge of "acne is a skin disease","it not only occurs in the period of adolescence" and "the disease can be prevented and cured",which accordingly accounted for 80.65％,69.16％ and 65.49％ of the total patients respectively.However,the awareness of acne patients to heredity,high sugar and dairy products as risk factors for acne was insufficient,which accounted for 48.72％,42.40％ and 18.25％ of the total patients,respectively.Gender,age,educational level,occupation and health knowledge were the main factors affecting the cognitive level of patients;the survey also found that men,patient with educational level of junior high or even lower educational condition,occupation of labor workers or farmers and patients were lack of health education with poor knowledge of the genetics and dietary were risk factors for acne;patients with age over 36 years or with mild illness had poor knowledge of dietary risk factors for acne;the difference was statistically significant (P＜0.05).The analysis of the influence of cognitive status on medical treatment behavior and skin care showed that the better the cognition,the higher the probability of patients would choose medical treatment as the first choice as well as choosing functional skin care products;the difference was statistically significant (P＜0.05).The consistency of assessment of the severity of acne by doctors and patients was poor (Kappa value ＜0.4),and the assessment of severity of acne by patients was more serious than doctors' assessment.Conclusions Patient's cognitive status will affect their medical behavior and skin care,and there is also a phenomenon that patients have a more serious assessment of their acne condition.It is suggested that health education for acne patients should be strengthened in clinical medicine so as to improve their knowledge of acne as well as preventing from acne effectively.

Objective To explore the expression of aquaporin-2 (AQP-2) in human fetus kidney and amniotic fluid at different stages of pregnancy.Methods Twenty-two cases of aborted fetuses' kidneys were collected.They were divided into 3 groups according to the pregnancy age:8 cases in 17-23 + 6 weeks,8 cases in 24-31 +6 weeks,and 6 cases in 32-38 +6 weeks.Western blot was used to examine the expression of AQP-2 in the kidney.Twenty-four cases of the amniotic fluid were collected,and they were divided into 3 groups according to the pregnancy age:10 cases in 17-23 +6 weeks,6 cases in 24-31 +6 weeks,and 8 cases in 32-38 +6 weeks.Eight cases of healthy adult morning urine were collected as positive controls.The AQP-2 protein in the amniotic fluid was detected with the method of enzyme-linked immunosorbent assay (ELISA) and the osmotic pressure of amniotic fluid at different stages of the pregnancy was measured with the freezing point osmometer.Results The expression of AQP-2 was increased with the extending of pregnancy age,and the AQP-2 expressions in fetus kidney of 17-23 +6 weeks,24-31 + 6 weeks and 32-38 +6 weeks were 0.986 ± 0.335,1.566 ± 0.272,and 2.080 ± 0.246,respectively,and the difference was significant (P ＜ 0.05).The AQP-2 detected from amniotic fluid was positively correlated with the result of AQP-2 in the kidney(r =0.985,P ＜ 0.05),and the AQP-2 expression also increased with the extending of pregnancy age:17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks and adult urine was (30.253 ±5.843) mg/L,(35.103 ±7.271) mg/L,and (42.580 ± 1.230) mg/L and (46.493 ± 0.450) mg/L,respectively.The osmolality of the amniotic fluid of 17-23 +6 weeks,24-31 +6 weeks,32-38 +6 weeks was (272.600 ± 4.827) mmol/L,(252.00 ± 15.360) mmol/L,and (261.750 ±5.560) mmol/L,respectively,and the difference was significant(P ＜0.05).Conclusions The AQP-2 expression in human fetus kidneys has good correlation with amniotic fluid,which indicates that the level of AQP-2 of the amniotic fluid may reflect the expression of AQP-2 in the fetus kidney.