ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Endotoxins are common exogenous pyrogens. Excessive endotoxins in medical devices and injections can lead to serious consequences such as sepsis, septic shock, and even death. Therefore, endotoxin detection plays a crucial role in medical, pharmaceutical, and food sectors. The wide application of Limulus amebocyte lysate (LAL) has led to a sharp decline in the number of horseshoe crabs. Moreover, the LAL assay has limitations such as interbatch variations and difficulty in quantification. The recombinant factor C (rFC) assay is stable between batches, highly sensitive, and capable of quantitation, and thus it can be used as an alternative for the LAL assay. However, the high cost and complex procedures involved in producing recombinant factor C have limited the widespread application of this method. In order to simplify the preparation and reduce the production cost of recombinant factor C, this study focuses on the production of recombinant factor C based on the baculovirus expression system. Multiple measures such as a high-yield and anti-apoptotic vector qBac-IIIG, the optimal signal peptide, and the optimized codon were used to reach the goal of endotoxin detection with cell supernatant. This method simplifies the steps of protein purification. The sensitivity of the supernatant reached 0.05 EU/mL in a 1-L fermentation system, and 500 000 detecting reactions can be supported per liter of fermentation broth. This study increases the yield and activity of recombinant factor C, simplifies the procedures of protein purification, and reduces the cost, laying a foundation for the promotion and application of recombinant factor C in endotoxin detection.
Animals ; Recombinant Proteins/genetics* ; Horseshoe Crabs/chemistry* ; Baculoviridae/metabolism* ; Endotoxins/analysis* ; Protein C/biosynthesis* ; Genetic Vectors/genetics* ; Arthropod Proteins/genetics* ; Enzyme Precursors ; Serine Endopeptidases

Background:Postoperative nutritional status and nutritional support therapy are important driving factor for clinical outcomes in patients after lung transplantation.This study aims to evaluate the relationship between mNUTRIC scores and prognosis in patients after lung transplantation.Methods:A retrospective inclusion of 253 patients who underwent lung transplantation at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 2020 to December 2022.The nutritional risk in patients after lung transplantation is much higher than in other critically ill patients.To explore the optimal threshold,patients were divided into three groups based on the tertiles of mNUTRIC scores,and clinical outcomes were compared.The predictive ability of the mNUTRIC score was analyzed using receiver operating characteristic(ROC)curve.The appropriate threshold was determined using the Youden index based on the highest combined sensitivity and specificity.Results:Among 253 patients,the 30-day mortality rate was 14.2%.The death group had higher age and BMI,with APACHE II,SOFA,and mNUTRIC scores all higher than those in the survival group.The median mNUTRIC score in the death group was 5.00(3.00～6.00).The higher the mNUTRIC score,the greater the gradual increase in 30-day mortality rate.When the mNUTRIC score was 4～6,the patient mortality rate was 21.21%,and when 7～9,it was 42.31%.The Q3 group had significantly prolonged mechanical ventilation time,was more prone to delayed weaning,had longer ICU length of stay,and higher tracheotomy rate.Multivariate Cox regression analysis and Kaplan-Meier survival curve showed that mNUTRIC score is an independent risk factor for 30-day mortality,with mortality rate increasing as the score increased(P<0.001).The area under the ROC curve(AUC)for mNUTRIC score was 0.765(95%CI:0.686,0.644).According to the Youden index,the optimal cutoff value is when mNUTRIC score equals 3.5,used to predict high nutritional risk and 30-day mortality in lung transplant patients.Conclusion:The mNUTRIC score has a good predictive effect on the prognosis of patients after lung transplantation and is expected to be applied in clinical practice as a routine assessment tool to help clinicians perform postoperative nutritional risk stratification.

Objective:To investigate the protective effect of Xuebijing injection on acute lung injury (ALI) associated with cardiopulmonary bypass (CPB) by regulating the apoptosis of polymorphonuclear neutrophils (PMN).Methods:Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), CPB model group (CPB group) and Xuebijing pretreatment group (XBJ group) according to the random number table method, with 10 rats in each group. Rats in the CPB group and XBJ group undergoing CPB procedures for 60 minutes. Rats in the Sham group did not undergo CPB. Rats in the XBJ group received intraperitoneal injection of 4 mL/kg Xuebijing injection 2 hours before CPB. Rats in the Sham group and CPB group were injected with an equal amount of normal saline. 4 hours after CPB, arterial blood was collected for blood gas analysis to calculate respiratory index (RI), and lung tissue of rats was collected for determination of lung index (LI) and pulmonary water containing rate. PMN in bronchoalveolar lavage fluid (BALF) were collected and the activity of caspase-3 was detected. The apoptosis rate was detected by flow cytometry. The expressions of microRNA-142-3p (miR-142-3p) and FoxO1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The protein expression of FoxO1 was detected by Western blotting. In addition, HL-60 cells were divided into control oligonucleotide transfection group, miR-142-3p mimics transfection group, and miR-142-3p inhibitor transfection group. After 48 hours of transfection, the activity of miR-142-3p binding to FoxO1 was detected using dual luciferase reporter genes.Results:Compared with Sham group, RI, LI and pulmonary water containing rate were significantly increased in CPB group. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly decreased, the expression of miR-142-3p was decreased, and the expression of FoxO1 protein was increased. However, compared with CPB group, RI, LI and pulmonary water containing rate were significantly decreased in XBJ group [RI: 0.281±0.066 vs. 0.379±0.071, LI: 4.50±0.26 vs. 5.71±0.42, pulmonary water containing rate: (80.31±32.50)% vs. (84.59±3.41)%, all P < 0.01]. The caspase-3 activity and apoptosis rate of PMN obtained from BALF were significantly increased [caspase-3 activity: 0.350±0.021 vs. 0.210±0.014, apoptosis rate: (15.490±1.382)% vs. (8.700±0.701)%, both P < 0.01], the expression of miR-142-3p was significantly up-regulated (2 -ΔΔCt: 2.61±0.17 vs. 0.62±0.05, P < 0.01), and the protein expression of FoxO1 was decreased [FoxO1/GAPDH (relative expression level): 0.81±0.04 vs. 1.22±0.06, P < 0.01]. However, there was no statistically significant difference in FoxO1 mRNA expression among the three groups. The bioinformatics analysis results showed that miR-142-3p can bind to the FoxO1 3'untranslated region (3'UTR). In HL-60 cells, compared with control oligonucleotide transfection group, the transfection of miR-142-3p mimics could reduce the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 0.48±0.06 vs. 1.00±0.05, P < 0.01], however, the transfection of miR-142-3p inhibitor increased the expression of FoxO1 protein [FoxO1/GAPDH (relative expression level): 1.37±0.21 vs. 1.00±0.05, P < 0.05]. But, transfection with miR-142-3p mimics or inhibitor had no effect on FoxO1 mRNA expression. The luciferase reporter gene showed that miR-142-3p could bind to the FoxO1 3'UTR to inhibit FoxO1 expression. Conclusion:Xuebijing injection may promote the apoptosis of pulmonary alveolar PMN through the miR-142-3p/FoxO1 axis, and play a role in the prevention and treatment of CPB-induced ALI.

Objective:Explore the feasibility and advantages of using proximal and distal ends of thoracodosal artery and vein as recipient vessels in deep inferior epigastric perforator flap immediate breast reconstruction.Methods:The clinical data of patients who underwent breast reconstruction surgery using the proximal and distal ends of the thoracodorsal vein as recipient vessels at the Department of Breast and Thyroid Surgery of the Second Affiliated Hospital of Hainan Medical University from March 2022 to June 2023 were analyzed retrospectively. Preoperative examinations included thoracoabdominal angiography and color Doppler ultrasonic localization of the main trunk and perforators of the inferior epigastric vessels. The procedure began with mastectomy and axillary lymph node dissection, followed by the isolation of bilateral perforators and the main trunk of the abdominal flap. The main trunks of the bilateral inferior epigastric arteries were then transected, and their vascular pedicles exposed and anastomosed respectively to the proximal and distal ends of the thoracodorsal artery and vein. Both arteries and veins were joined end-to-end. The flap after trimming and reconstruction was then implanted into the cavity left after mastectomy through the incision. Breast positioning was performed with the patient in a knee-bent and hip-flexed position. After adjusting the shape of the reconstructed breast. The donor site was closed, the umbilicus was reconstructed, drainage tubes were placed, and the breast incision was closed. Postoperative follow-up monitored complications associated with the flap and patient satisfaction with the breast reconstruction, utilizing a self-assessment method.Results:Four female patients were included, aged (46.0±6.5) years, ranging from 37 to 52 years. All four patients had bilateral vascular pedicles in the donor area, with three patients having thoracodorsal vessels at the distal and proximal ends as recipient vessels, and one patient having anterior serratus branch of the thoracodorsal vessels at the distal and proximal ends. All drainage tubes were removed within 7 to 10 days after surgery. Patients were discharged. Follow-up period ranged from 1 to 15 months, averaging 6 months. The patients recovered well postoperatively, with no flap-related complications occurring. All four patients were satisfied with the result of the reconstruction.Conclusion:The simultaneous application of the proximal and distal ends of the thoracodorsal artery and vein can ensure the safety of flap survival while reducing damage to the ribs and intercostal muscles, achieving better aesthetic result.

Objective:Explore the feasibility and advantages of using proximal and distal ends of thoracodosal artery and vein as recipient vessels in deep inferior epigastric perforator flap immediate breast reconstruction.Methods:The clinical data of patients who underwent breast reconstruction surgery using the proximal and distal ends of the thoracodorsal vein as recipient vessels at the Department of Breast and Thyroid Surgery of the Second Affiliated Hospital of Hainan Medical University from March 2022 to June 2023 were analyzed retrospectively. Preoperative examinations included thoracoabdominal angiography and color Doppler ultrasonic localization of the main trunk and perforators of the inferior epigastric vessels. The procedure began with mastectomy and axillary lymph node dissection, followed by the isolation of bilateral perforators and the main trunk of the abdominal flap. The main trunks of the bilateral inferior epigastric arteries were then transected, and their vascular pedicles exposed and anastomosed respectively to the proximal and distal ends of the thoracodorsal artery and vein. Both arteries and veins were joined end-to-end. The flap after trimming and reconstruction was then implanted into the cavity left after mastectomy through the incision. Breast positioning was performed with the patient in a knee-bent and hip-flexed position. After adjusting the shape of the reconstructed breast. The donor site was closed, the umbilicus was reconstructed, drainage tubes were placed, and the breast incision was closed. Postoperative follow-up monitored complications associated with the flap and patient satisfaction with the breast reconstruction, utilizing a self-assessment method.Results:Four female patients were included, aged (46.0±6.5) years, ranging from 37 to 52 years. All four patients had bilateral vascular pedicles in the donor area, with three patients having thoracodorsal vessels at the distal and proximal ends as recipient vessels, and one patient having anterior serratus branch of the thoracodorsal vessels at the distal and proximal ends. All drainage tubes were removed within 7 to 10 days after surgery. Patients were discharged. Follow-up period ranged from 1 to 15 months, averaging 6 months. The patients recovered well postoperatively, with no flap-related complications occurring. All four patients were satisfied with the result of the reconstruction.Conclusion:The simultaneous application of the proximal and distal ends of the thoracodorsal artery and vein can ensure the safety of flap survival while reducing damage to the ribs and intercostal muscles, achieving better aesthetic result.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

The community teaching bases play an important role in training of general practice talents. To raise the training quality, the development of their own capacity is crucial, but community medical institutions also need close cooperation with the departments of general practice in medical schools and the higher-level general hospitals. This article discusses the integration model of management, teaching and research in general practice talent training based on the cooperation of community teaching bases with relevant governmental departments, professional societies/associations, general hospitals and medical schools.