Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

Objective To investigate the role of mitochondrial antiviral signaling protein(MAVS)in viral infection-triggered generalized pustular psoriasis(GPP)in children.Methods This retrospective case-control study enrolled 80 GPP patients aged 0～18 years from Children's Hospital of Chongqing Medical University(from October 2013 to April 2019).Whole-exome sequencing identified rare MAVS variants associated with GPP.Pathogenicity of variants was predicted using Mutation Taster,Disease Association,SIFT,and CADD bioinformatics tools.Sanger sequencing validated variants,followed by construction of wild-type(WT)and mutant MAVS expression plasmids transfected into HEK 293 cells.Protein expression was assessed by Western blot.Dual-luciferase reporter gene assays measured IFNB1 and NF-κB transcriptional activity.Genotype distribution of the MAVS c.171dupT/p.H57fs variant was analyzed using Fisher's exact test.Results This study enrolled 80 pediatric GPP patients(aged 0～18 years).Whole-exome sequencing identified five rare MAVS variants,with bioinformatics analyses predicting deleterious effects on protein stability and function.Western blot demonstrated that the c.171dupT mutation in GPP patients significantly reduced full-length MAVS expression(P<0.001);dual-luciferase assays further revealed this variant impaired MAVS-mediated IFNB1 transcriptional activation by 85%(P<0.001),abrogated NF-κB signaling pathway activation(P<0.001),but exhibited no dominant-negative effect on wild-type MAVS function(P>0.05).Conclusion The MAVS c.171dupT frameshift variant may contribute to infection-triggered GPP in children,suggesting its potential as a genetic biomarker for GPP susceptibility.

[Objective] To investigate the protective effect of Salvia miltiorrhiza injection (SMI) on the kidneys of HBOC-CHP01 resuscitated haemorrhagic shock rats. [Methods] A 50% haemorrhagic shock rat model was established, with 12 rats divided into two groups: SMI + HBOC-CHP01 group and HBOC-CHP01 group, with 6 rats in each group. The rats in the SMI+ HBOC-CHP01 group were given an equal volume of HBOC-CHP01 for resuscitation after haemorrhagic shock, and an 8 mL/kg dose of SMI. Rats in the HBOC-CHP01 group were resuscitated by administering an equilibrium blood loss volume of HBOC-CHP01 and given an 8 mL/kg dose of 0.9% NaCl solution. Blood was taken from rats at five points: before bloodletting (baseline), during haemorrhagic shock (HS), immediately after resuscitation (RS0h), 1 h after resuscitation (RS1h), and 24 h after resuscitation (RS24h). A blood gas analyser was used to detect the lactate level (Lac), glucose content (Glu), residual base (BEecf), pH, bicarbonate (HCO3-), high iron haemoglobin (MetHb). White blood cells (WBC), platelets (PLT), haemoglobin content (Hb), carboxyhaemoglobin (COHb) were detected using a quintuple classification. Blood creatinine (SCr), uric acid (UA), kidney-related indexes were detected using biochemistry instrument. Kidney tissues of the rats were taken after 24 h of resuscitation and after execution, and the inflammation of kidneys of the rats of the two groups was analyzed using HE staining. Fluorescence staining was used to detect the level of ROS in the kidneys of rats in both groups. [Results] At RS 0h, the Beecf, Glu and Lac levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group, and the pH level of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group, and the Glu levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group at RS 1h. At RS 0h, the WBC, PLT and COHb contents of rats in the SMI+HBOC-CHP01 group were all significantly higher than those of rats in the HBOC-CHP01 group, and at RS 1h, the WBC content of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group; at RS 1h, the UA content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the SCr content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the inflammation level of kidney tissues of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC -CHP01 group rats, and the ROS and MPO levels in the kidney tissues of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group. [Conclusion] The combination of Salvia miltiorrhiza injection during the resuscitation of rats with severe haemorrhagic shock by HBOC-CHP01 can alleviate renal injury by reducing inflammatory response and oxidative stress.

[Objective] To extract hemoglobin (Hb) from red blood cells using osmotic pressure swelling method, expected to achieve a hemoglobin dissolution rate of ≥80% and a cell membrane integrity rate of ≥70%. [Methods] Human umbilical cord blood red blood cells were used as raw materials and phosphate buffer solution was used as the swelling solution for red blood cells. A three factor three-level orthogonal experiment (n=3) was conducted to determine the optimal matching conditions for selecting the osmolality molar concentration of phosphate buffer solution, pH value of hypotonic phosphate buffer solution and volume ratio of hypotonic phosphate buffer solution to washed red blood cells. Red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions. The hemoglobin dissolution rate and cell membrane integrity rate were checked. In the expanded comparative experiment, red blood cell swelling solution samples (n=6) were prepared by the optimal matching conditions and the original process conditions, which was filtered by ultrafiltration membranes. The filtration time and hemoglobin yield were checked. [Results] The optimal matching conditions for preparing red blood cell swelling solution were obtained through orthogonal experiment as follows: osmotic pressure molar concentration was 30 mOsmol/Kg, pH was 7.8, and phosphate buffer to red blood cell volume ratio was 6∶1. On the basis of the above conditions, the red blood cell swelling solution sample was compared with the original process sample: the hemoglobin dissolution rate was (82.4±1.8)% vs (78.6±3.0)% (P<0.05), and the cell membrane integrity rate was (65.8±4.0)% vs (28.7±2.3)% (P<0.05). In the expanded comparative experiment, the optimal matching conditions were compared with the original process conditions: filtration time(s) (327±9) vs (434±13) (P<0.05), and hemoglobin yield was (72.3±1.2)% vs (66.0±1.4)% (P<0.05). [Conclusion] Compared with the original preparation process, the hemoglobin extraction process which optimized through orthogonal experiments greatly reduces the cell membrane fragmentation rate and minimizes the entry of cell membrane matrix into the target solution, ensuring a slightly higher hemoglobin dissolution rate, and reducing the preparation difficulty for the subsequent cell membrane separation and further purification.

OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Objective:To quantify thoracic and abdominal movements during breathing using inertial measurement units (IMUs) and to build a machine learning model which identifies the abdominal breathing (AB) pattern.Methods:Ten rehabilitation therapists formed the study′s professional group, while 15 patients receiving AB training comprised the validation group. Two synchronized IMUs were applied to capture breathing motions during natural breathing (NB), deep breathing (DB) and AB. Six kinematic features were extracted from each respiratory cycle, and inter-group and inter-pattern differences were analyzed. Correlation analysis was also performed with manually measured changes in thoracic and abdominal circumferences. A support vector classification model for AB pattern detection was then developed using data from the professional and validation groups.Results:A total of 1113 respiratory cycles were extracted and analyzed. The breathing pattern significantly influenced all of the kinematic features studied (0.21≤partial η 2≤0.65, all P≤0.001). The ranges of the angles in medial-lateral axis of the IMUs showed strong correlation with the changes in abdominal and thoracic circumferences (ρ1=0.928, ρ2=0.807, P≤0.001 in both cases). A greater range of abdominal angles was found during AB compared to the other patterns. The best of the models achieved an F1 score of 0.970 (sensitivity: 0.983, specificity: 0.980) in validation. Conclusions:AB generates the greatest abdominal movement. Combining IMUs and machine learning can provide real-time quantification of chest movement and accurate detection of AB during breathing training.

AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P＜0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P＜0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P＜0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P＜0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

AIM:To investigate the impact of es-ketamine-mediated opioid-free anesthesia(OFA)on postoperative gastrointestinal function in patients undergoing laparoscopic distal gastrectomy for gas-tric cancer.METHODS:A total of 150 pa-tients,scheduled for elective laparoscopic distal gas-trectomy for gastric cancer and meeting the inclu-sion and exclusion criteria,were randomly assigned to either the OFA group or the opioid-based anes-thesia(OBA)group using a random number ta-ble,with 75 patients in each group.The OFA group was administered an anesthesia regimen pri-marily consisting of esketamine,while the OBA group received conventional opioid anesthesia,pri-marily consisting of sufentanil and remifentanil.The primary outcome measure was postoperative flatus time,defined as the interval from the end of sur-gery to the first passage of gas.RESULTS:The OFA group exhibited a shorter postoperative flatus time compared to the OBA group(P＜0.01).Intraopera-tive blood loss and norepinephrine consumption were significantly less in the OFA group compared to the OBA group(P＜0.05);the postoperative HADS-D score was better in the OFA group than in the OBA group,and both the OFA and OBA groups showed significantly lower postoperative HADS-A and HADS-D scores compared to their preoperative levels(P＜0.05);the incidence rate of abdominal distension was significantly lower in the OFA group compared to the OBA group(P＜0.05).CONCLUSION:The use of esketamine-mediated opioid-free anesthesia can expedite gastrointestinal function recovery,reduce hospital stay duration,and decrease postoperative adverse reactions in patients undergoing laparo-scopic distal gastrectomy for gastric cancer.