ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.

【Objective】 To explore the safety of transrectal ultrasound-guided transperineal injection of sodium hyaluronate to expand the Dirichlet gap in laparoscopic radical prostatectomy. 【Methods】 A total of 14 healthy male purebred beagle dogs were selected and randomly divided into 2 groups, with 7 in either group.The control group was treated with conventional laparoscopic radical prostatectomy, while the experimental group was treated with laparoscopic radical prostatectomy after 2.5 mL sodium hyaluronate was injected into the Dirichlet gap under the guidance of transrectal ultrasound.The total operation time, prostate separation time, intraoperative blood loss and rectal status of the 2 groups were observed. 【Results】 After the injection of sodium hyaluronate into the Dirichlet gap between the prostate and the rectum, no rectal tissue was found in the prostate, and no obvious damage was found in the posterior rectum in either groups.The postoperative hemoglobin (HGB) was [(118.70±2.56) g/L vs.(122.10±2.19) g/L, P=0.02]; the total operation time was [(141.40±9.80) min vs.(119.10±9.16) min, P<0.05]; the prostate separation time was [(24.99±1.75) min vs.(16.64±2.34) min, P<0.05]; the amount of bleeding was [(47.43±4.32) mL vs.(34.86±5.18) mL, P<0.05] in the control group and experimental group. 【Conclusion】 Laparoscopic radical prostatectomy performed after 2.5 mL of sodium hyaluronate injection into the Dirichlet gap under the guidance of transrectal ultrasound can shorten the total operation time, the separation and resection time of the prostate, and reduce the amount of bleeding, which can improve and reduce the incidence of rectal injury, and prove the feasibility of this approach for prostatic cancer.

Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?

Objective:To evaluate the diagnostic accuracy of a noninvasive physiological parameter-based early sepsis screening model for elderly patients in comparison to the systemic inflammatory response syndrome(SIRS)and quick sequential organ failure assessment(qSOFA)scores.Methods:A retrospective study was conducted using data from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database.The study focused on patients who were admitted to the intensive care unit(ICU)within 24 hours and were categorized into septic and non-septic groups based on the presence or absence of sepsis.Baseline data and patient outcomes were recorded.Additionally, the SIRS score and qSOFA scores within 24 hours of ICU admission were calculated.Physiological parameters that showed statistical significance in the univariate analysis included respiratory rate, heart rate, level of consciousness, body temperature, systolic blood pressure, and urine output.These parameters were then included in Logistic regression models.The specificity and sensitivity of the regression model for sepsis screening were calculated, and receiver operating characteristic(ROC)curves were plotted.The areas under the ROC curves(AUCs)of the screening model, SIRS, and qSOFA scoring systems were compared.Results:A total of 53 150 ICU hospitalization records were screened, and 23 681 patients with infection or suspected infection within 24 hours were included.Among them, 18 277 patients had sepsis.The 28-day mortality rate for septic patients was higher compared to non-septic patients(13.5% vs.5.1%, χ2=285.131, P<0.001).The baseline data within 24 hours showed significant differences between the two groups in terms of heart rate, respiratory rate, body temperature, state of consciousness, 24-hour urine output, and systolic blood pressure(all P<0.001).These variables were included in the regression equation: ∑β iX i=2.055+ 0.285(temperature: 0/1)+ 0.172(respiratory rate: 0/1)+ 0.073(heart rate: 0/1)+ 1.204(mental status: 0/1)-0.022(systolic blood pressure)+ 0.227(classification of urine output: 0/1/2), P=1/[1+ EXP(-∑β iX i)].The regression model diagnosed sepsis ROC area in young and middle-aged patients as 0.726(95% CI: 0.718 to 0.735), which was significantly higher than the SIRS score(0.585, 95% CI: 0.576 to 0.595)and the qSOFA score(0.676, 95% CI: 0.667 to 0.685)(both P<0.001).In elderly patients, the regression model diagnosed sepsis ROC area as 0.671(95% CI: 0.663 to 0.679), which was also significantly higher than the SIRS score(0.572, 95% CI: 0.563 to 0.580)and the qSOFA score(0.631, 95% CI: 0.623 to 0.639)(both P<0.001). Conclusions:The early sepsis diagnosis model, which utilizes noninvasive physiological parameters, has shown higher accuracy when compared to the SIRS and qSOFA scores.However, it is important to note that its accuracy is lower in elderly patients as compared to young and middle-aged patients.This indicates the necessity for further optimization of the model in order to improve its performance in diagnosing sepsis in the elderly.

Objective:To investigate whether malignant tumors are an independent risk factor for short-term mortality in elderly patients with sepsis in the intensive care unit(ICU), and to examine the dose-response relationship between the sequential organ failure assessment(SOFA)score and short-term mortality in this patient population.Methods:A retrospective analysis was conducted on elderly sepsis patients aged 80 and above from the Medical Information Mart for Intensive Care(MIMIC-Ⅳ)database spanning from 2008 to 2019.The patients were categorized into a tumor group and a non-tumor group based on the presence of malignant tumors, and a comparison was made between the baseline data and prognosis of these two groups.Furthermore, patients were classified into survival and mortality groups based on their ICU survival status within 28 days, and a comparison of baseline data was performed.Logistic regression analysis was employed to identify the risk factors associated with short-term mortality.Additionally, probability unit regression was utilized to model the dose-response relationship between the SOFA score and short-term mortality.Results:A total of 53 150 medical records were screened, identifying 5 126 elderly sepsis patients aged 80 and above.Among them, 754 had malignant tumors and 264 had metastatic tumors.The 28-day mortality rate in the tumor group was significantly higher than in the non-tumor group[26.79%(202/754) vs.18.85%(824/4 372), χ2=24.85, P<0.001].Logistic regression analysis revealed age( OR=1.073, 95% CI: 1.040-1.108, P<0.001), Charlson comorbidity index(CCI)excluding tumors( OR=1.134, 95% CI: 1.067-1.205, P<0.001), blood lactate concentration at ICU admission( OR=1.111, 95% CI: 1.048-1.179, P<0.001), mechanical ventilation( OR=1.603, 95% CI: 1.176-2.187, P=0.003), and SOFA score( OR=1.227, 95% CI: 1.182-1.273, P<0.001)as risk factors for short-term mortality.Conversely, CCI( OR=0.957, 95% CI: 0.867-1.057, P=0.380), use of vasoactive drugs( OR=1.370, 95% CI: 0.902-2.081, P=0.140), malignant tumors( OR=1.131, 95% CI: 0.449-2.848, P=0.794), and metastasis of malignant tumors( OR=1.799, 95% CI: 0.930-3.477, P=0.081)were not associated with short-term mortality.The dose-response curve illustrated that as the SOFA score increased, patients' 28-day mortality rate also rose, reaching 50% at a SOFA score of 11 and exceeding 80% at a score of 20. Conclusions:Malignant tumors and tumor metastasis do not appear to be independent risk factors for short-term mortality in elderly sepsis patients in the ICU.Instead, the short-term mortality rate of these patients seems to be correlated with the SOFA score in a dose-response manner.

Objective To investigate the effects and mechanisms of LINC00657 on oxidative glucose deprivation (OGD)-induced injury in mouse hippocampal neurons. Methods Mouse hippocampal neuron cell line HT22 was given OGD treatment to establish an injury model, with normally cultured HT22 cells as controls. The si-NC, si-LINC00657, microRNA(miR)-NC, and miR-224-3p mimics were transfected into HT22 cells, followed by OGD treatment. Co-transfection of si-LINC00657 and anti-miR-NC, or co-transfection of si-LINC00657 and anti-miR-224-3p, was performed in HT22 cells before OGD treatment. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of LINC00657 and miR-224-3p. CCK-8 assay and flow cytometry were used to detect cell viability and apoptosis rate, respectively. Kits were used to detect the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA). Dual-luciferase reporter gene assay was used to detect the effect of miR-224-3p overexpression on the luciferase activity of wild-type LINC00657 vector (WT-LINC00657) and mutant LINC00657 vector (MUT-LINC00657). Results Compared with controls, the expression of LINC00657 was upregulated and the expression of miR-224-3p was downregulated in OGD-induced HT22 cells (P < 0.05). Compared with transfection of si-NC or miR-NC, transfection of si-LINC00657 or miR-224-3p mimics resulted in increased cell viability, SOD activity, and GSH-Px activity, as well as decreased apoptosis rate, LDH activity, and MDA level(P < 0.05). Overexpression of miR-224-3p reduced the luciferase activity of WT-LINC00657 (P < 0.05). Compared with cells co-transfected with si-LINC00657 and anti-miR-NC, cells co-transfected with si-LINC00657 and anti-miR-224-3p showed decreased cell viability, increased apoptosis rate, increased LDH activity and MDA level, and decreased SOD and GSH-Px activities (P < 0.05). Conclusion Interference with LINC00657 can promote cell proliferation, inhibit apoptosis and oxidative stress response by upregulating miR-224-3p, thereby alleviating OGD-induced injury in mouse hippocampal neurons.

ObjectiveTo investigate the influencing factors for the prognosis of patients with acute－on－chronic liver failure （ACLF）， and to establish a short－term prognostic model. MethodsA retrospective analysis was performed for the baseline clinical data of 247 patients with ACLF who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Xi’an Jiaotong University， from January 2011 to December 2016， and the patients were divided into survival group and death group. The two groups were compared to identify the influencing factors for prognosis； a prognostic model was established， and the receiver operating characteristic （ROC） curve was used to assess its predictive efficacy and determine the optimal cut－off value. The independent－samples t test was used for comparison of normally distributed continuous data between groups， and the Mann－Whitney U rank sum test was used for comparison of non－normally distributed continuous data between groups； the Fisher’s exact test or the Pearson’s chi－square test was used for comparison of categorical data between groups. The univariate and multivariate logistic regression analyses were used to investigate the independent risk factors for 28－ and 90－day prognosis， and the Kaplan－Meier method was used to plot the 28－day survival curves. ResultsA total of 220 patients with ACLF were included based on the inclusion and exclusion criteria； there were 148 patients in the 28－day survival group and 72 patients in the 28－day death group， with a 28－day transplantation－free survival rate of 67.27%； there were 115 patients in the 90－day survival group and 105 patients in the 90－day death group， with a 90－day transplantation－free survival rate of 52.27%. The logistic regression analysis showed that female sex （odds ratio ［OR］=2.149， P=0.030）， high Model for End－Stage Liver Disease （MELD） score （OR=1.120， P<0.001）， and low lymphocyte count （OR=0.411， P=0.002） were independent risk factors for 28－day prognosis， and an LS－MELD model for 28－day prognosis was established as Logit （28－day prognosis）=－3.432+0.765×sex－0.890×lymphocyte count×10^－9+0.113×MELD（1 for male sex and 2 for female sex）. The ROC curve analysis showed that this model had an optimal cut－off value of 0.35， and then the patients were divided into low LS－MELD group （≤0.35） and high LS－MELD group （>0.35）； the low LS－MELD group had a significantly higher 28－day survival rate than the high LS－MELD group （P<0.001）. ConclusionPeripheral blood lymphocyte count combined with sex and MELD score has a certain value in predicting the short－term prognosis of ALCF patients.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.