Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

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.

Objective　To compare the changes in the genetic diversity of Anopheles minimus through the research on the population genetic characteristics of Anopheles minimus between different years in Nabang Town, Yingjiang County, Yunnan Province. Methods Anopheles mosquitoes were collected by light traps in Nabang Town, Yingjiang County, Yunnan Province in May 2014 and May 2021. After morphological identification, each mosquito was individually stored in separate tubes for further analysis. DNA of Anopheles minimus was extracted using kits. Microsatellite sequences in the template DNA were amplified using eight pairs of fluorescent primers, and the resulting products were subjected to capillary electrophoresis by a sequencing company. PopGen32 software was used to calculate the observed number of alleles (Na), effective number of alleles (Ne), observed heterozygosity (Ho), expected heterozygosity (He), and Shannon's information index (I) for individual microsatellite loci and population groups. PIC-CALC software was used to calculate the polymorphic information content (PIC). Results A total of 158 mosquitoes belonging to 6 Anopheles species were captured in 2014, while 529 mosquitoes belonging to 5 Anopheles species were captured in 2021. The composition ratio of Anopheles minimus among the mosquito species differed significantly between 2014 and 2021 (χ2=70.48, P<0.01). For 8 microsatellite loci, a total of 85 alleles were detected, a range of 6-20 alleles per locus and an average of 10.625 alleles. Ne ranged from 1.717 to 7.797, with an average of 4.011. The highest PIC was found in the am4 locus, and the lowest in the am25 locus. For the population groups, 77 alleles were found in 2014, and 62 alleles were found in 2021. Ne ranged from 1.630 to 8.658, with an average of 4.147 in 2014. Ne ranged from 1.760 to 6.744, with an average of 3.698 in 2021. The average Ho was 0.641 in 2014 and 0.650 in 2021, while the average He was 0.699 in 2014 and 0.691 in 2021. The Shannon's index ranged from 0.774 to 2.493 in 2014, with an average of 1.579, and from 0.938 to 2.224 in 2021, with an average of 1.464. Na, Ne, I, and PIC were all higher in 2014 compared to 2021, with Na: 9.625>7.750, Ne: 4.147>3.698, I: 1.579>1.464, and PIC: 0.655>0.640, respectively. Conclusions The populations of Anopheles minimus in Nabang Town, Yingjiang County, exhibited high levels of polymorphism in both 2014 and 2021. However, the genetic diversity of the population in 2021 was lower than that in 2014.

This article summarizes the domestic and international research progress of recombinant human follicle stimulating hormone(rFSH).According to relevant guidelines and application cases,the general requirements and common problems for non-clinical evaluation of rFSH are summarized.The clinical development prospects of long-acting rFSH products which is a hot research topic in recent years are analyzed and corresponding suggestions are given in order to provide reference for related work.

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

AIM: To evaluate the effect of remimazolam on early postoperative cognitive function in elderly patients with hip fracture based on a randomized controlled trial. METHODS: A total of 106 elderly patients, aged 65-90 years, ASA grade Ⅱ or III, who underwent hip fracture surgery under combined spinal-epidural anesthesia in the Sixth Affiliated Hospital of Wenzhou Medical University from December 2022 to June 2023 and met the inclusion criteria, were selected and randomized into remimazolam group (group R) and propofol group (group P) according to the random number table, with 53 cases in each group. Patients in group P received a slow intravenous injection of propofol at a dose of 0.3-0.5 mg / kg (injection time of 1min), followed by a pump infusion at 0.5-3 mg · kg