Objective:To explore the difference between selective lobar bronchial block and main bronchial block in thoracoscopic surgery in children.Methods:A retrospective cohort study was conducted to analyze the clinical data of 150 children undergoing thoracoscopic surgery admitted to Henan Children's Hospital, Zhengzhou Children's Hospital, and Children's Hospital Affiliated to Zhengzhou University from December 2019 to December 2022. In the examination of the electronic medical record, 80 children were found to have selective lobar bronchial block, which was used as the study group, and 70 children were matched as the control group.Compare the general data of children in the two groups, such as age, gender, weight, surgical time, and other data. Compare the two groups with respect to hypoxemia, degree of pulmonary collapse, atelectasis, and number of bronchial blocker shifts. Compare the heart rate(HR), mean arterial pressure(MAP), degree of pulmonary collapse, and airway pressure(PAW) at different time points in the two groups[before single lung ventilation(OLV)(T1), 10 min after OLV(T2), and 10 min after OLV(T3)] Difference in alveolar arterial oxygen partial pressure(AaDO 2) levels. Results:Comparison of the incidence of hypoxemia, bronchial blocker displacement, and atelectasis in children in the study group were statistically significant( P<0.05). The results of repeated measurement of variance showed that there was statistically significant difference in the inter subject effects of HR and MAP levels at different time points between the two groups based on time factors( P<0.05). The results of repeated measurement of variance showed that there was statistical significance between the inter-subjective effects of the levels of PAW and AaDO 2 at different time points of the two groups with time factor as the source, group as the source, and intra-subjective effects with time and group interaction as the source( P<0.05). The levels of PAW and AaDO 2 in the study group at time points T2 and T3 were significantly lower than those in the control group, and the differences between the groups were statistically significant( P<0.05). Conclusion:The effect of selective lobobronchial blockade in thoracoscopic surgery in children is ideal, which can effectively improve the ventilation and related oxygenation of children, and reduce the occurrence of complications such as atelectasis and hypoxemia.

Objective:To explore the function of MDM2 and its relationship with p53 at the cellular level during H 2O 2 induced oxidative damage. Methods:MLE-12 HALI cell models were established using 0.5 mmol/L H 2O 2, and were divided into three groups: normal control group, H 2O 2 injury group, H 2O 2+MDM2 overexpressed group, and H 2O 2+MDM2 shRNA group. Infection of MLE-12 cells with adenovirus vector overexpressing and silencing MDM2; Using immunoprecipitation (Co-IP) to analyze the interaction between MDM2 and p53; Western blotting was used to detect the protein expression levels of MDM2, p53, Bcl-2, Bax, and cleared caspase-3 after HALI modeling; Measure the apoptosis rate of cells in each group. Results:After transcriptome sequencing,the p53 signaling pathway closely related to HALI. Compared with the normal group, the expression of MDM2 in the H 2O 2 injury group was lower ( P<0.05); Compared with the H 2O 2 injury group, overexpression of MDM2 resulted in a decrease in the apoptosis rate of MLE-12 cells ( P<0.05), a decrease in the expression levels of p53, Bax, and cleared caspase-3 proteins, and an upregulation of MDM2 and Bcl-2 protein expression ( P<0.05). Compared with the H 2O 2 injury group, when MDM2 was silenced, the cell apoptosis rate increased ( P<0.05), and the expression levels of p53, Bax, and cleared caspase-3 proteins were upregulated, while the expression levels of MDM2 and Bcl-2 proteins decreased ( P<0.05). Co-IP experiments showed that MDM2 binds to p53 protein. Conclusions:MDM2 can exert a protective effect on HALI by inhibiting MLE-12 cell apoptosis through the p53/Bcl-2/Bax axis.

Abstract OBJECTIVE To design and synthesize a novel bacteriochlorin derivative and study its antitumor effect. METHODS The target compound was synthesized from bacteriochlorin derivative via reduction, bromination after reacted with methyl 2-[4-(hydroxymethyl)phenoxy]acetate via etherification and hydrolysis. NCI-H460 BALB/c nude mice model was used to detect the distribution of drugs in various tissues, the antitumor effect of the target compound was studied by photodynamic therapy. RESULTS A novel bacteriochlorin derivative was synthesized, and structure was characterized by 1H-NMR, 13C-NMR, MS and UV. The target compound expressed fine distribution in tissues, and it had a great inhibit effect on the growth of tumor cells. CONCLUSION After introducing hydrophilic group into the structure of bacteriochlorin derivative, the tissue selectivity and antitumor effect has been improved, which is worthy of further study.

ObjectiveTo develop and validate a predictive model to individually predict the risk of patients with stroke in the eICU Collaborative Research Database for early clinical identification and intervention. MethodIndividual patient data （200 859 cases） from a national multicenter cohort study （eICU database） were selected， and the patients with stroke in neurological diseases （9 037 cases） were selected for statistical analysis. The main outcome was hospital mortality. The Glasgow Coma scale （GCS） was used to divide all patients with stroke into stroke in meridian and stroke in viscera （GCS≤14 for stroke in viscera and GCS=15 for stroke in meridian）. The patients were then divided into a training set and a test set according to 7∶3， respectively， to evaluate the differences in hospital mortality between the two groups. The multivariate logistic regression was used to analyze the related factors affecting the prognosis of the two groups， and a predictive model was established. Receiver operator characteristic （ROC） curves were used to assess the discrimination of the predictive model. ResultThe predictive model based on 9 037 patients with stroke was established. The predictors of the stroke in meridian （4 475 cases） included pulmonary infection， mechanical ventilation， acute physiology， and chronic health status scoring system Ⅳ （APACHE Ⅳ） score. The predictors of the stroke in viscera （4 562 cases） included anticoagulation therapy （AT）， mechanical ventilation， acute physiology， and APACHE Ⅳ score. According to the predictors， the predictive models of the stroke in meridian and the stroke in viscera were constructed， respectively. The areas under the curve （AUC） of ROC of the training set and the test set of the predictive models of the stroke in meridian were 0.845 ［95% confidence interval （CI） （0.811， 0.879）］ and 0.807 ［95% CI （0.751， 0.863）］， respectively. The areas under the ROC curve of the training set and test set of the predictive models of the stroke in viscera were 0.799 ［95% CI （0.781， 0.817）］ and 0.805 ［95% CI （0.778， 0.832）］， respectively. The AUC of the predictive model of the training set and the test set were both above 0.7. ConclusionThe model established in this study can conveniently， directly， and accurately predict the hospital mortality risk of patients with stroke. Physicians and other healthcare professionals can use this predictive approach to provide early care planning and clinical interventions for patients with stroke during their hospital stay.

BACKGROUND: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis. METHODS: Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer Operetta™ was used to obtain high-resolution images of three-dimensional organoids. RESULTS: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h. CONCLUSIONS This study provides the primary intestinal in vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.
Mice ; Animals ; Lipopolysaccharides/toxicity* ; Sepsis ; Intestinal Diseases ; Tumor Necrosis Factor-alpha ; Disease Models, Animal ; Organoids ; RNA

Background::Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods::Sepsis was induced in C57BL/6 wild type (WT) mice and Atf4-knockdown ( Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Results::CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6C hi monocytes), the precursor cells of gMacs. Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice, Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes ( TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting from Atf4 knockdown was not caused by the enhanced inflammatory effect of Ly6C hi monocytes and gMacs. Conclusion::ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.

Objective: To investigate the clinical research of Guo's Liulian therapy in treating acute pancreatitis intestinal mucosal barrier dysfunction and provide reference for the patients with acute pancreatitis. Methods: The 68 patients with acute pancreatitis who were admitted to our hospital from September 2016 to May 2018 were selected as study subjects. According to the random number table method, the patients were divided into the observation group and the control group, with 34 cases in each group. The patients in the control group were treated with conventional western medicine. The patients in the observation group were treated with Guo's Liulian therapy on the basis of the above treatment. The time of intestinal paralysis was compared between the two groups. The changes of intestinal mucosal barrier function and serum inflammatory factor related indexes before and after treatment were analyzed in the two groups. The difference of therapeutic effects between the two groups was observed. Results: In the observation group, the abdominal pain relief time, abdominal distention relief time, bowel sound recovery time, and first bowel anus defecation time were significantly lower than those in the control group (t=7.621, 5.332 6.625, 8.762, all Ps<0.01). After treatment, serum LPS, DAO, ET, D-lactic acid, TNF-α, IL-1, IL-6, IL-8, and IL-10 and urine L/M were significantly lower in the observation group, while the serum ITF and MFG-E8 were significantly higher in the observation group (t=9.856, 6.974, 9.784, 16.068, 9.550, 12.506, 22.343, 16.625, 6.774, 23.469, 20.118, 23.031, all Ps<0.01). Conclusions The Guo's Liulian therapy treatment of acute pancreatitis in patients with intestinal mucosal barrier dysfunction can reduce the palsy remission time, reduce inflammation, increase serum ITF, MFG-E8 levels, repair of intestinal permeability, and improve the intestinal barrier function.

Intestinal?barrier?act?as?the?crucial?defender?against?pathogen?invasion,?and?is?indispensable?in?maintaining?tissue?homeostasis?both?locally?and?systemically.?Severe?disease?can?lead?to?impaired?intestinal?barrier.?In?addition?to?cause?a?variety?of?gastrointestinal?diseases,?intestinal?barrier?damage?can?also?worsen?the?disease?progression?in?critically?ill?patients.?Innate?lymphoid?cells?(ILCs)?is?a?group?of?newly?defined?innate?immune?cells?which?have?some?characteristics?as?adaptive?immune?cells.?Group?3?innate?lymphoid?cells?(ILC3),?which?mainly?reside?at?gut?associate?mucosal?tissue,?have?been?reported?to?play?a?critical?role?in?maintaining?intestinal?barrier?function.?After?a?brief?introduction?about?its?origination?and?classification,?we?will?focus?on?function?of?ILC3?physiologically?and?pathologically,?and?provide?a?new?theoretical?basis?for?maintaining?intestinal?barrier?function?under?pathological?conditions?in??this?review.

Objective To investigate the role and mechanism of ulinastatin on the hyper-permeability of vascular endothelial cell induced by matrix metalloproteinase-9 (MMP-9). Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro to establish a complete monolayer vascular endothelial cell model. The monolayer vascular endothelial cells were randomly divided into three groups: blank control group [phosphate buffered saline (PBS) added], MMP-9 model group (1 mg/L MMP-9 added) and ulinastatin group (1 mg/L MMP-9 and 1 000 kU/L ulinastatin added). The permeability of monolayer vascular endothelial cells was measured by fluorescein isothiocyanate (FITC)-labeled dextran (FD40) leaking method; the soluble vascular endothelial cells calcium dependent adherin (VE-cadherin) concentration in culture solution was determined by enzyme linked immunosorbent assay (ELISA);the protein expression levels of zonular occlusion protein-1 or tight junction (ZO-1), VE-cadherin, claudin-5 were detected by Western Blot and immunofluorescence methods. Results Compared with the blank control group, the permeability of vascular endothelial cells in MMP-9 model group was significantly increased [(cm2/h, ×10-2):3.35±0.56 vs. 0.94±0.06, P < 0.05]; the concentrations of soluble VE-cadherin in the Transwell upper and lower chambers were increased significantly [upper chamber (μg/L): 5.02±0.40 vs. 3.83±0.42, lower chamber (μg/L):4.92±1.05 vs. 3.24±1.24, both P < 0.05]; the protein expression levels of ZO-1, VE-cadherin and claudin-5 were significantly decreased [ZO-1/β-actin: 0.152±0.067 vs. 0.262±0.090, VE-cadherin/β-actin: 0.137±0.048 vs. 0.246±0.094, claudin-5/β-actin: 0.148±0.062 vs. 0.336±0.119, all P < 0.05], and obvious rupture sites appeared in their fluorescent patterns, and fluorescent particles were significantly reduced; compared with MMP-9 model group, the permeability of vascular endothelial cells in ulinastatin group was significantly decreased [(cm2/h, ×10-2): 1.80±0.34 vs. 3.35±0.56, P < 0.05]; the soluble VE-cadherin concentrations were significantly reduced in upper and lower chambers than those in the MMP-9 model group [upper chamber (μg/L): 4.41±0.37 vs. 5.02±0.40, lower chamber (μg/L):3.85±1.04 vs. 4.92±1.05, both P < 0.05], the expressions of endothelial junction protein were significantly increased in ulinastatin group (ZO-1/β-actin: 0.229±0.097 vs. 0.152±0.067, VE-cadherin/β-actin: 0.236±0.089 vs. 0.137±0.048, claudin-5/β-actin: 0.262±0.101 vs. 0.148±0.062, all P < 0.05], and the continuity of their fluorescent patterns and fluorescent particles were both increased. Conclusion The in vitro experiment showed that the hyper-permeability of vascular endothelial cells induced by MMP-9 can be attenuated by ulinastatin through decreasing the destruction of VE-cadherin and maintaining the protein expression levels of ZO-1, VE-cadherin and claudin-5 in vascular endothelial cells.

" Filial piety" is China's traditional culture.It not only educates the offspring to be grateful and to repay good deeds,but more importantly guides people to take up social responsibilities and obligations.However,there are always contradiction dilemmas between loyalty and filial piety in reality.With the change of the times,this kind of contradiction is getting more prominent.Rethinking the choice of " raising the children but not provi-ding for the elderly" or choosing for helplessness,the causes of which include: the development of medical technol-ogy aggravates the contradiction between the ability and the cost of providing for the elderly,the contradiction be-tween the prolongation of the life of the elderly and the limitation of their children's ability to support them; Chi-na's one-child policy for more than 30 years has weakened the support capacity of the offspring; urban develop-ment leads to population migration and challenges family pension; the instability of family structure affects providing for the elderly; social pension is inadequately prepared and so on.To guarantee intergenerational equity and im-prove people's quality of life,it should advocate the scientific view of providing for the elderly,which must respect the elderly's autonomy,improve and promote the assessment and supervision of basic needs such as living will,hospice care,and medical abandonment.Through carrying out relevant research,it should establish a systematic project of good Chinese-style scientific pension and improve the social pension security system.