Bamboo leaf flavonoids(BLF)are compounds extracted from bamboo leaves,possessing properties including antioxidant,antimicrobial and anti-inflammatory properties.This study aimed to investigate the effects of BLF on liver damage,antioxidant function,and related gene expression in rats induced by diquat(DQ).Thirty-two 5-week-old male Sprague-Dawley(SD)rats were randomly divided into four experimental groups:the control group(Con),1 000 mg/kg BLF group(BLF),DQ stress group(DQ),and 1 000 mg/kg BLF+DQ stress group(BLF-DQ).The results showed that compared to the Con,the DQ group exhibited significantly decreased serum AST lev-els(P＜0.05),as well as decreased levels of T-AOC,GPX,SOD,and CAT in the liver(P＜0.05),and increased MDA levels in rats(P＜0.05).Additionally,the gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2 in the liver were significantly reduced(P＜0.05).In contrast,1 000 mg/kg BLF significantly decreased serum AST and ALT levels(P＜0.05),increased levels of T-AOC,GPX,CAT,and SOD in liver(P＜0.05),and significantly increased gene expression of HO-1,GPX,CAT,SOD1,Nrf2,and NQO1(P＜0.05).Compared to the DQ group,BLF-DQ significant-ly decreased liver index(P＜0.05),reduced serum AST and ALT levels(P＜0.05),increased lev-els of CAT,GPX,and T-AOC in liver(P＜0.05),decreased MDA levels(P＜0.05),and signifi-cantly upregulated gene expression levels of HO-1,GPX,CAT,SOD1,and Nrf2(P＜0.05).These findings indicated that BLF alleviate liver damage caused by DQ stress in rats,improve liver an-tioxidant function inhibition,activate the Nrf2 signaling pathway and PINK/Parkin mitophagy-re-lated gene expression.

Optimizing the management of medical service appointment is an important measure to enhance the patient′s medical experience and promote the high-quality development of hospitals. In 2022, a tertiary comprehensive hospital in Jiangsu Province focused on the demand for digital appointments, and carried out coordinated management of intelligent appointment for medical examination both inside and outside the hospital, online and offline. By constructing an intelligent examination appointment system, enriching appointment categories, exchanging appointment information, improving supporting services, and establishing appointment supervision mechanisms, this practice provided intelligent, personalized, and precise examination appointment services for patients in multi-campus hospitals and member units of medical group. The average waiting time of patients for CT, MRI, and ultrasound examinations in this hospital decreased from 7.43 h, 8.75 h, and 4.63 h in 2021 to 4.63 h, 4.72 h, and 2.18 h in 2023, respectively, as well as the average satisfaction rate of patients with examination appointments increased from 90.7% to 96.5%. The intelligent examination appointment management had achieved good results, which could provide references for other hospitals to optimize appointment of medical services.

OBJECTIVE: To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. METHODS: A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. RESULTS: A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ² = 71.850, P < 0.001). CONCLUSIONS Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.
Humans ; Male ; Female ; Aged ; Retrospective Studies ; Sepsis/diagnosis* ; Critical Care ; Intensive Care Units ; Prognosis ; Hemoglobins ; ROC Curve

Sepsis is a systemic disease with severe health consequences, and it was redefined in 2016 as a life-threatening organ dysfunction caused by an abnormal host response to infection and is a global public health priority. In recent years, there has been increasing recognition of the role of dysregulated micronutrient iron metabolism in the pathogenesis of sepsis. The concept of ferroptosis, an iron-dependent, non-apoptotic mode of cell death characterized by the accumulation of lipid reactive oxygen species (ROS), was first proposed by Dixon et al. in 2012. As a novel mode of programmed cell death, ferroptosis differs in morphological and biochemical characteristics from various forms of cell death, such as apoptosis, autophagy, necrosis and lysis. Recent studies have shown that ferroptosis plays an important regulatory role in the development of sepsis and has become a research focus and highlight for the diagnosis and prognosis of related diseases. Therefore, this paper reviews the latest developments in ferroptosis in sepsis, in order to further understanding its pathogenesis and providing new therapeutic targets for sepsis-related organ dysfunction.

Objective:To evaluate the effect of hydrogen on the immunosuppressive status of septic rats.Methods:SPF healthy adult male Sprague-Dawley rats, aged 7-8 weeks, weighing 220-260 g, were studied.This study was performed in two parts.Part Ⅰ The rats were divided into 2 groups: sepsis group (Sep group, n=36) and sham operation group (Sham group, n=12). The model of sepsis was established by cecal ligation puncture in anesthetized rats.The histocompatibility DR antigen (HLA-DR)/CD14 + monocyte level in peripheral blood was detected by flow cytometry immediately after CLP and at 1, 2, 3 and 4 days after CLP.The establishment of sepsis-induced immunosuppression model was considered successful when the levels of HLA-DR/CD14 + monocyte in peripheral blood were <30%.Part Ⅱ Twelve rats with sepsis-induced immunosuppression were randomly selected and divided into 2 groups ( n=6 each) by a random number table method: sepsis immunosuppression group (Sep-IS group), sepsis immunosuppression plus hydrogen treatment group (Sep-IS+ H group). Another 12 rats were selected and divided into 2 groups ( n=6 each) by a random number table method: sham operation group (Sham group) and sham operation plus hydrogen group (Sham+ H group). In Sep-IS+ H group, 67% hydrogen was inhaled for 1 h starting from the time point immediately after successful establishment of sepsis-induced immunosuppression and from 6 h after establishment, and 67% hydrogen was inhaled for 1 h at the corresponding time points in Sham+ H group.The levels of helper T lymphocytes 17 (Th17 cells), regulatory T lymphocytes (Treg cells) and HLA-DR/CD14 + monocyte in peripheral blood were determined by flow cytometry immediately after the end of hydrogen inhalation mentioned above (T 0, T 1) and at 12 h after establishing the model (T 2). Results:Part Ⅰ Compared with Sham group, the levels of HLA-DR/CD14 + monocyte in peripheral blood were significantly decreased at 1-4 days after CLP in Sep group ( P<0.05). Part Ⅱ Compared with Sham group, the level of HLA-DR/CD14 + monocytes in peripheral blood was significantly decreased, and the levels of Treg and Th17 cells were increased at each time point in Sep-IS and Sep-IS+ H groups ( P<0.05), and no significant change was found in the parameters mentioned above in Sham+ H group ( P>0.05). Compared with Sep-IS group, the level of HLA-DR/CD14 + monocytes in peripheral blood was significantly increased at T 1, 2, the levels of Th17 cells were increased at T 2, and the levels of Treg cells were decreased at T 1, 2 in Sep-IS+ H group ( P<0.05). Conclusion:Hydrogen can improve the immunosuppressive state of septic rats.

The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guideline) was recently released. The guidelines summarized the evidences from literatures through to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guideline (96 recommendations), although the total number of recommendations in the 2021 guideline is similar, the number of "strong recommendations (recommend)" in 2021 guideline has dropped significantly, while as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guideline has also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guideline did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data & artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guideline tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.

Objective:To investigate the molecular mechanism of SUMO specific protease 1 (SENP1) regulating endoplasmic reticulum stress transcription regulator X-box binding protein 1 (XBP1) in the proliferation of liver cancer cells.Methods:The pathological samples of 180 patients with primary liver cancer in the Department of Hepatobiliary Surgery of Inner Mongolia People′s Hospital from January 2012 to January 2020 were collected. The expressions of SENP1 and XBP1 in liver cancer, adjacent tissues and different liver cancer cell lines were detected. The correlation between SENP1 positive expression and clinicopathological features of liver cancer patients was analyzed. Immunofluorescence and flow cytometry were used to detect the effect of SENP1 siRNA on XBP1 and apoptosis. SUMO1 expression on XBP1 surface was detected and the effect of SENP1 siRNA on SUMO formation of XBP1 was detected by immunoprecipitation.Results:The expression levels of SENP1 in liver cancer and adjacent tissues were 16.332±4.371 and 6.840±2.238, with a statistically significant difference ( t=-5.073, P=0.017). The expression levels of XBP1 in liver cancer and adjacent tissues were 6.641±2.482 and 16.051±4.452, with a statistically significant difference ( t=3.592, P=0.032). The expression of SENP1 was correlated with stage ( χ2=6.724, P=0.010) and metastasis ( χ2=6.265, P=0.012). Immunofluorescence staining showed that the expressions of XBP1 in L02 (0.509±0.219), MHCC97-L (0.092±0.022) and HCCLM3 (0.086±0.014) cells were significantly different ( F=6.378, P=0.004), while the expression of XBP1 in MHCC97-L and HCCLM3 cells was significantly lower than that in L02 cells ( P=0.023; P=0.021). The expression levels of SENP1 in L02, MHCC97-L and HCCLM3 cells were 0.109±0.079, 0.802±0.392 and 0.921±0.352, with a statistically significant difference ( F=7.783, P=0.004), while the expression level of SENP1 in MHCC97-L and HCCLM3 cells was significantly higher than that in L02 cells ( P=0.039; P=0.016). After transfection of SENP1 siRNA into MHCC97-L and HCCLM3 cells, the expressions of XBP1 increased (0.462±0.192, t=3.664, P=0.022; 0.524±0.203, t=3.383, P=0.028); the expressions of SENP1 decreased (0.153±0.093, t=2.790, P=0.049; 0.165±0.104, t=3.568, P=0.023). The results of flow cytometry showed that the apoptosis rates of L02, MHCC97-L, HCCLM3, MHCC97-L+ SENP1 siRNA and HCCLM3+ SENP1 siRNA cells were (20.80±3.11)%, (2.02±1.20)%, (0.12±0.01)%, (7.01±1.80)%, (6.20±2.01)%, with a statistically significant difference ( F=1.025, P=0.030). The apoptosis rate of MHCC97-L and HCCLM3 cells was significantly lower than that of L02 cells ( P=0.040; P=0.010), the apoptosis rate of MHCC97-L+ SENP1 siRNA and HCCLM3+ SENP1 siRNA cells was significantly higher than that of MHCC97-L and HCCLM3 cells (both P=0.009). Immunoprecipitation results showed that the expression levels of XBP1 in L02, MHCC97-L, HCCLM3, MHCC97-L+ SENP1 siRNA, HCCLM3+ SENP1 siRNA cells were 11.943±5.043, 7.467±1.903, 2.051±0.913, 9.532±3.012, 8.731±3.102, and SUMO1 expression levels were 10.158±4.005, 5.871±3.075, 1.941± 0.907, 8.658±4.878, 7.169±4.677, and the differences were statistically significant ( F=11.730, P=0.010; F=8.548, P=0.001). The expressions of XBP1 and SUMO1 in MHCC97-L ( P=0.028; P=0.038) and HCCLM3 ( P<0.001; P<0.001) cells were lower than those in L02 cells, XBP1 expression in HCCLM3+ SENP1 siRNA cells was higher than that in HCCLM3 cells ( P=0.001), and SUMO1 expression in MHCC97-L+ SENP1 siRNA cells and HCCLM3+ SENP1 siRNA cells respectively was higher than that in MHCC97-L ( P=0.045) and HCCLM3 ( P=0.039) cells. Conclusion:SENP1 siRNA can promote the apoptosis of liver cancer cells by up regulating SUMO modification of XBP1.

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.

Objective: To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO₂/PtcCO₂) in the treatment of septic shock. Methods: A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluationⅡ (APACHEⅡ), the length of ICU stay and 28-day prognosis were collected; PtcCO₂, PtcO₂, PtcO₂/PtcCO₂ ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO₂), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binary Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients. Results: A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHEⅡ score and PtcCO₂ were higher and PtcO₂/PtcCO₂ ratio was lower in death group [APACHEⅡ: 28.33±6.35 vs. 21.61±6.64, PtcCO₂ (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO₂/PtcCO₂ ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO₂/PtcCO₂ ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO₂/PtcCO₂ ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L): 3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO₂ and ScvO₂. The PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO₂/PtcCO₂ ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy and APACHEⅡ score were risk factors of prognosis [PtcO₂/PtcCO₂ ratio: odds ratio (OR) = 7.876, P = 0.026; APACHEⅡ score: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO₂/PtcCO₂ ratio, APACHEⅡscore and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO₂/PtcCO₂ ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0%, and the specificity was 73.3%. In addition, the patients were divided into two groups according to whether the 6-hour PtcO₂/PtcCO₂ ratio was greater than 1.42. The results showed that: compared with the PtcO₂/PtcCO₂ < 1.42 group, the APACHEⅡ score in PtcO₂/PtcCO₂ ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower. Conclusions Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.

OBJECTIVE: To evaluate microcirculatory changes after bundle therapy and prognostic values of the ratio of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (PtcO₂/PtcCO₂) in the treatment of septic shock. METHODS: A retrospective analysis was conducted. Patients with septic shock admitted to department of intensive care unit (ICU) of Northern Jiangsu People's Hospital from July 2017 to February 2019 were enrolled. The gender, age, infection site, acute physiology and chronic health evaluation II (APACHE II), the length of ICU stay and 28-day prognosis were collected; PtcCO₂, PtcO₂, PtcO₂/PtcCO₂ ratio, arterial lactate (Lac), central venous oxygen saturation (ScvO₂), mean arterial pressure (MAP) were measured before treatment (at admission) and 6 hours after bundle treatment. According to the 28-day prognosis, the patients were divided into survival group and death group, and the differences of each index between the two groups were compared. The risk factors of prognosis were analyzed by binary Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the related indicators for the 28-day mortality of septic shock patients. RESULTS: A total of 78 patients with septic shock were enrolled, with 47 cases in survival group and 31 cases in death group. Compared with survival group, APACHE II score and PtcCO₂ were higher and PtcO₂/PtcCO₂ ratio was lower in death group [APACHE II: 28.33±6.35 vs. 21.61±6.64, PtcCO₂ (mmHg, 1 mmHg = 0.133 kPa): 51.80±19.05 vs. 38.17±6.79, PtcO₂/PtcCO₂ ratio: 1.20±0.72 vs. 1.80±0.81, all P < 0.05]. Compared with before treatment, the PtcO₂/PtcCO₂ ratio, Lac, MAP were substantially improved at 6 hours of bundle therapy [PtcO₂/PtcCO₂ ratio: 1.76±0.81 vs. 1.56±0.82, Lac (mmol/L): 3.74±2.40 vs. 4.42±2.60, MAP (mmHg): 83.34±7.58 vs. 71.00±5.36, all P < 0.05], and there was no changes in PtcCO₂ and ScvO₂. The PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy in the survival group was significantly higher than before treatment and was higher than that in death group (2.13±0.75 vs. 1.80±0.81, 1.19±0.53, both P < 0.05). There was no significant difference in PtcO₂/PtcCO₂ ratio of death group before and after treatment (1.19±0.53 vs. 1.20±0.72, P > 0.05). The binary Logistic regression showed that PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy and APACHE II score were risk factors of prognosis [PtcO₂/PtcCO₂ ratio: odds ratio (OR) = 7.876, P = 0.026; APACHE II score: OR = 0.846, P = 0.035]. ROC curve analysis showed that 6-hour of PtcO₂/PtcCO₂ ratio, APACHE II score and 6-hour Lac level could predict 28-day mortality in septic shock patients, and the area under curve (AUC) was 0.864, 0.784, and 0.752 respectively. The cut-off value of 6-hour PtcO₂/PtcCO₂ ratio for predicting mortality in septic shock patients was 1.42, the sensitivity was 87.0%, and the specificity was 73.3%. In addition, the patients were divided into two groups according to whether the 6-hour PtcO₂/PtcCO₂ ratio was greater than 1.42. The results showed that: compared with the PtcO₂/PtcCO₂ < 1.42 group, the APACHE II score in PtcO₂/PtcCO₂ ≥ 1.42 group was lower, the 6-hour Lac level was lower, 24-hour Lac reaching standard rate was higher and the 28-day mortality was lower. CONCLUSIONS Compared with the traditional metabolic parameters, the improvement of early microcirculatory perfusion in patients with septic shock can reflect the effect of bundle therapy. The PtcO₂/PtcCO₂ ratio at 6 hours of bundle therapy can be used as a new index to predict the prognosis of patients with septic shock which supports the monitoring and evaluation of microcirculation in the early stage of treatment in septic shock.
Carbon Dioxide ; Humans ; Microcirculation ; Oxygen ; Prognosis ; ROC Curve ; Retrospective Studies ; Shock, Septic/therapy*