OBJECTIVE: To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism. METHODS: DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 μmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC₅₀) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture. RESULTS: Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC₅₀ was 20.56 μmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production. CONCLUSION Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/pharmacology* ; Pyroptosis ; Cell Line ; RNA, Messenger ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism. METHODS: Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation. RESULTS: In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001). CONCLUSION Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.
Animals ; Mice ; Humans ; Lymphoma, Extranodal NK-T-Cell/pathology* ; Forkhead Box Protein O3/metabolism* ; bcl-2-Associated X Protein/pharmacology* ; Mice, Nude ; Signal Transduction ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Chemokine CCL22/pharmacology*

Objective:To investigate the diagnostic value of ultrasonic measurement of optic nerve sheath diameter (ONSD) and optical disk elevation (ODE) for intracranial hypertension in patients with cerebral venous sinus thrombosis(CVST).Methods:A total of 50 patients with CVST who underwent lumbar puncture and ONSD examination in the Department of Neurology and Emergency Department of Xuanwu Hospital, Capital Medical University from January 2021 to December 2021 were retrospectively enrolled. After lumbar puncture, the patient′s initial intracranial pressure was recorded. Normal ICP was defined as ICP between 80 and 200 mmH 2O, and increased ICP was defined as ICP>200 mmH 2O. Fifty patients with CVST were divided into normal ICP group (14 cases) and increased ICP group (36 cases). The differences of baseline data, ONSD and ODE between the two groups were compared, and the receiver operating characteristic (ROC) curve was generated. The area under the curve (AUC) and the diagnostic cut-off value of ONSD were analyzed. Spearman correlation analysis was used to analyze the correlation between ONSD, ODE, CVST involvement range scores and intracranial pressure. Results:①There were no significant differences in gender, age and body mass index between the normal ICP group and the increased ICP group (all P>0.05). ②The ONSD and ODE in the increased ICP group were higher than those in the normal ICP group, and the differences were statistically significant [(4.83±0.33)mm vs (4.21±0.21)mm, (0.67±0.44)mm vs (0.24±0.29)mm, all P<0.001]. Spearman correlation analysis showed that ONSD and ODE were positively correlated with intracranial pressure ( rs=0.74, 0.51, all P<0.001). ③The extent of CVST involvement in the intracranial hypertension group was higher than that in the normal intracranial pressure group, and the difference was statistically significant [5.0(3.0, 7.5) vs 2.5(2.0, 5.0), P=0.015]. Spearman correlation analysis showed that CVST involvement score was positively correlated with intracranial pressure ( rs=0.43, P<0.001). ④In the diagnosis of intracranial hypertension in patients with cerebral venous sinus thrombosis, the AUC of ONSD was 0.935, the best diagnostic threshold of ONSD was 4.5 mm, the sensitivity was 0.81, and the specificity was 0.93. Conclusions:ONSD and ODE measured by ultrasound are reliable imaging methods to identify intracranial hypertension in patients with CVST.

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

Aim To investigate the effect of p-hydroxybenzaldehyde ( HD) on intestinal fibrosis in mice based on mouse intestinal fibrosis model and in vitro EMT model,and to explore the underlying mechanism Methods HE staining, Masson staining, immunohisto-chemistry ,qPCR, Western blot and other experimental methods were used to verify the effect of HD on intestinal fibrosis in mice and the potential mechanism. Results In vivo experiments showed that compared with the normal group, the DSS-induced intestinal fibrosis model group had shortened colon, increased colon his-topathological score, increased collagen volume fraction, and significantly increased collagen I expression. After treatment with 4, 10, and 25 mg • kg

Objective To evaluate the molluscicidal effect of 25% wettable powder of pyriclobenzuron sulphate (WPPS) against Oncomelania snails in hilly schistosomiasis-endemic regions and test its toxicity to fish. Methods In October 2020, a snail-infested setting which had been cleared was selected in Nanjian County, Yunnan Province and divided into several blocks, and the natural snail mortality was estimated. 25% WPPS was prepared into solutions at concentrations of 1 and 2 g/L, and 25% wettable powder of niclosamide ethanolamine salt (WPNES) was prepared into solutions at a concentration of 2 g/L. The different concentrations of drugs were sprayed evenly, and the same amount of water was used as blank control. Snails were surveyed using the systematic sampling method 1, 3 and 7 days post-treatment, and snail survival was observed. A fish pond was selected in Nanjian County, and 2 kg 25% WPPS was evenly sprayed on the water surface to allow the effective concentration of 20 g/L. Fish mortality was estimated 8, 24, 48 and 72 h post-treatment. Results One-day treatment with 1 and 2 g/L WPPS and 2 g/L WPNES resulted in 97.99%, 97.99% and 94.11% adjusted snail mortality rates (χ² = 3.509 and 3.509, both P values > 0.05), and the adjusted snail mortality was all 100% 3 d post-treatment with 1 and 2 g/L WPPS and 2 g/L WPNES, while 7-day treatment with 1 and 2 g/L WPPS and 2 g/L WPNES resulted in 91.75%, 86.57% and 57.76% adjusted snail mortality rates (χ² = 14.893 and 42.284, both P values < 0.05). Treatment with 2 g/L WPPS for 72 h resulted in a 0.67% cumulative mortality rate of fish. Conclusion 25% WPPS is effective for snail control and highly safe for fish, which is feasible for use in hilly schistosomiasis-endemic regions.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Objective:To study the clinical characteristics of children with adenovirus pneumonia complicated with liver injury and the understanding of clinicians.Methods:The children diagnosed with community-acquired adenovirus pneumonia were enrolled from January 1, 2013 to December 31, 2020. The clinical characteristics of the normal liver function group and the liver injured group were compared, and multivariate regression was applied.Results:Among the 3 294 enrolled children, 1 704 children had elevated alanine aminotransferase and/or aspartate aminotransferase on admission, and the liver function impairment rate was 51.7% (1 704/3 294), of which 1 671 cases were mildly injured (98.06%, 1 671/1 704), 28 cases were moderately injured (1.64%, 28/1 704), and 5 cases were severely injured (0.29%, 5/1 704). Compared with the normal liver function group, the proportion of male children in the liver injured group was higher (68.1% vs. 64.2%, P=0.017), and the age was younger[16(9, 30) months vs. 38(19, 53) months, P<0.001]. Children with liver injury were more likely to have wheezing (32.9% vs. 18.7%, P<0.001), shortness of breath (13.7% vs. 9.1%, P<0.001), and diarrhea (11.0% vs. 4.7%, P<0.001). The white blood cell counts, neutrophil counts and hemoglobin in the liver injured group were lower than those in the normal group, while the lymphocyte counts were higher than those in the normal group. The levels of creatine kinase, cardiac creatine kinase and lactate dehydrogenase were higher. The proportion of severe pneumonia in the liver injured group (26.9% vs. 11.2%, P<0.001) was higher than that in the normal liver function group, and the case fatality rate was significantly higher (1.47% vs. 0.25%, P<0.001). Comparing the probability of liver injury in children with mild and severe adenovirus pneumonia, it was found that the severe pneumonia group had more frequent liver injury (73.0% vs 46.6%, P<0.001), and both moderate and severe liver injury groups were higher than in the mild group. Further multivariate logistic regression analysis did not find a significant factor associated with the incidence of liver injury. Conclusions:The incidence of adenovirus pneumonia in children with liver injury was high, and mild injury is more common. Children with liver injury were younger, had more severe clinical symptoms such as wheezing and shortness of breath, and higher proportion of severe pneumonia and mortality. Among them, children with severe pneumonia had a higher proportion of liver injury, and moderate to severe injury was more common. The monitoring of children with different degrees of liver injury should be strengthened.

This paper reports 3 cases of acute hepatitis of unknown cause in children who met the case definition of WHO. Human adenovirus group C was detected in case 3, and the quantity of viral DNA was relatively high, which may be related to the liver function damage in the patient, but its role in pathogenesis needs further study to confirm.

Objective: To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Methods: Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. Results: The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P<0.05). After treatment, the scores of primary and secondary symptoms decreased in all three groups, with statistically significant intra-group differences (all P<0.05); the scores of primary symptoms were significantly different between the massage plus moxibustion group and the drug group (P<0.05); the scores of secondary symptoms in the massage plus moxibustion group and the massage group were significantly different from that in the drug group (both P<0.05). The differences in the time to recover normal bowel movement frequency among the three groups were not statistically significant (P>0.05). Conclusion: Ginger-partitioned moxibustion plus pediatric massage compared with pediatric massage or smecta monotherapy shows superior clinical efficacy in treating infantile diarrhea due to spleen deficiency, and has the advantages of appetite improvement, physique strengthening and short course.