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 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 This study aims to monitor the mRNA ratio of podocin to nephrin (PNR) in glomerular podocytes of early diabetic kidney disease (DKD) rat models. The feasibility of using PNR as an early diagnostic indicator for DKD was evaluated by comparing it with the urinary albumin-to-creatinine ratio (U-ACR). Additionally, the early intervention effects of valsartan and fosinopril sodium on DKD were compared. Methods The DKD rat model was established by caudal intravenous injection of streptozotocin (STZ) at a dosage of 60 mg/kg. The early changes in PNR and U-ACR were monitored and compared, followed by timely intervention with valsartan and fosinopril sodium. Hematoxylin and eosin staining (HE) was used to observe glomerular structure, while transmission electron microscopy examined the ultrastructure of glomerular podocytes. ResultsPNR reached the critical value(≥1) on day 9 after modeling, earlier than U-ACR, which reached the critical value(≥30 mg/g) on day 15. Intervention with valsartan and fosinopril sodium on day 9 after modeling significantly reduced U-ACR (P < 0.05), with low-dose valsartan showing better results than high-dose (P>0.05), while high-dose fosinopril sodium outperformed low-dose (P>0.05). Both low doses of valsartan and fosinopril sodium significantly reduced PNR (P<0.05), with no significant effect observed for high doses. The interventions with valsartan and fosinopril sodium improved and maintained glomerular structure and podocyte arrangement. ConclusionPNR changes earlier than U-ACR, indicating its potential as an early diagnostic marker for DKD in rats. Early intervention with valsartan and fosinopril sodium demonstrates a therapeutic effect on DKD in rats.

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 investigate the levels of microRNA (miR) -106b-5p and miR-760 in the serum of early lung cancer patients, and the clinical value of the combination of them and low-dose spiral CT in the diagnosis of early lung cancer.Methods:Ninety early lung cancer patients (lung cancer group) who underwent treatment in Cangzhou People's Hospital of Hebei Province from January 2022 to March 2023 were collected as research subjects, meantime, 90 patients with benign pulmonary lesions (benign pulmonary nodules) diagnosed by pathology were selected as the control group. The levels of miR-106b-5p and miR-760 in the serum of two groups were compared, the results of low-dose spiral CT examination were analyzed; receiver operating characteristic curve was drawn to determine the optimal cut-off values of serum miR-106b-5p and miR-760; four grid table method was applied to analyze the diagnostic efficacy of serum miR-106b-5p, miR-760 combined with low-dose spiral CT for early lung cancer.Results:The level of miR-106b-5p in lung cancer group was higher than that in control group (1.39±0.31 vs. 1.04±0.30), serum miR-760 level was lower than that in control group (0.75±0.24 vs. 1.02±0.26), with statistically significant differences ( t=7.70, P<0.001; t=7.24, P<0.001). The area under curve (AUC) of miR-106b-5p, miR-760 and low-dose spiral CT in the diagnosis of early lung cancer was 0.83, 0.81 and 0.82, the accuracy was 76.67%, 77.22% and 81.67%, the sensitivity was 84.44%, 81.11% and 76.67%, and the specificity was 68.89%, 73.33% and 86.67%, respectively. The AUC, accuracy, sensitivity, and specificity of serum miR-106b-5p, miR-760 combined with low-dose spiral CT in diagnosing early lung cancer were 0.96, 90.00%, 94.44%, and 85.56%, respectively. The accuracy of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=11.52, P=0.001; χ2=10.72, P=0.001; χ2=5.14, P=0.023), the sensitivity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 and low-dose spiral CT ( χ2=4.77, P=0.029; χ2=7.46, P=0.006; χ2=11.51, P=0.001), the specificity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p, miR-760 ( χ2=7.11, P=0.008; χ2=4.12, P=0.042) . Conclusion:The serum level of miR-106b-5p is significantly increased in early lung cancer patients, while the serum level of miR-760 is significantly reduced. The combination of miR-106b-5p, miR-760 and low-dose spiral CT has high diagnostic value for early lung cancer.

Objective:To improve the standard and quality of clinical trials, the possible risks of Investigator-Initiated Clinical Trial(IIT) approvals based on drug supply and security were discussed and suggestions were put forward.Methods:According to the laws and regulations and literature review, concerning experimental drug supply and security during project negotiation, the risk points of IIT approvals were comprehensively analyzed and suggestions were put forward.Results:There are four main types of risks in assessing IIT approvals in terms of drug supply and security: drug entry and sales, drug promotion, discounts of observation fees, and concept confusion. Healthcare institutions should pay attention to and coordinate the IIT approvals.Conclusions:IIT is a supplement and extension of Industry Sponsored Trial(IST), which should be actively carried out by healthcare institutions while also paying attention to the security and risk prevention of drug supply, ensuring a standardized and orderly manner.

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.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

The fundamental purpose of tissue-engineered skin development is to restore the skin barrier function of patients with severe skin injury, and this kind of product has become an ideal substitute for skin transplantation in clinic at present. With the development of three-dimensional bioprinting technology, the three-dimensional skin models constructed with complex structures such as skin appendages are also becoming increasingly mature. The stable three-dimensional skin model is widely used in skin physiological and pathological research, cosmetic safety and efficacy evaluation, and alternating animal experiments. In this paper, we introduced the three-dimensional bioprinting technology in categories, summarized the types of bio-inks commonly used for skin model construction, reviewed the recent advances of three-dimensional bioprinting technology applied in the field of skin tissue engineering, and explored and prospected the future directions of its research development and application fields.