BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

BACKGROUND:The inflammatory response of microglia is closely related to neuronal survival,regeneration,and functional recovery after spinal cord injury.Peroxiredoxin 1 is not only involved in the regulation of oxidative stress,but also has an important effect on cell proliferation,apoptosis,and inflammatory response.OBJECTIVE:To investigate the role and mechanism of peroxiredoxin 1 in the inflammatory response of microglia following spinal cord injury.METHODS:(1)Twelve female C57BL/6 mice were randomly divided into sham-operated(n=6)and spinal cord injury(n=6)groups.The sham-operated group was not modeled and acute spinal cord injury models were constructed in the spinal cord injury group using the modified Allen's method.Spinal cord tissue at the injured site was taken at 7 days after modeling and transcriptome sequencing was performed to identify differentially expressed genes.The expression of peroxiredoxin 1 in spinal cord tissues was verified using western blot and RT-qPCR.(2)Mouse microglia BV2 were divided into two groups:the control group was stimulated with lipopolysaccharide for 6 hours,and in the knockout group,lipopolysaccharide stimulation was applied for 6 hours at 24 hours after peroxiredoxin 1 was knocked down in the cells.RT-qPCR was performed to detect mRNA expression of peroxiredoxin 1,inflammatory factors(interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2),and western blot was performed to detect the expression of peroxiredoxin 1,inducible nitric oxide synthase,and reactive oxygen/mitogen-activated protein kinase signaling pathway proteins.Mouse microglia BV2 were treated in two groups:the control group was stimulated by hydrogen peroxide for 4 hours,and the knockout group was stimulated by hydrogen peroxide for 4 hours at 24 hours after knockdown of peroxiredoxin 1.The level of reactive oxygen species was detected by 2,7-dichlorodihydrofluorescein diacetate probe.RESULTS AND CONCLUSION:(1)Results from transcriptome sequencing,western blot and RT-qPCR confirmed that peroxiredoxin 1 expression levels in mouse spinal cord tissues were significantly higher in the spinal cord injury group than the sham-operated group(P＜0.05).(2)Peroxiredoxin 1 knockdown in microglial cells led to decreased expression of peroxiredoxin 1 mRNA and protein(P＜0.05),increased mRNA expression of interleukin 1β,interleukin 6,inducible nitric oxide synthase,tumor necrosis factor α,C-C motif chemokine ligand 2,and C-X-C motif chemokine ligand 2(P＜0.05),increased protein expression of inducible nitric oxide synthase,P-P38,P-JNK and P-ERK proteins(P＜0.05),and increased level of reactive oxygen species(P＜0.05).To conclude,peroxiredoxin 1 regulates microglial inflammation by targeting the reactive oxygen species/mitogen-activated protein kinase signaling pathway.

Hepatic encephalopathy(HE),a neuropsychiatric syndrome caused by acute or chronic liver failure or portosystemic shunting,is characterized by metabolic disturbances and varying degrees of cognitive dysfunction.HE is one of the most common complications and is the leading cause of mortality in cirrhotic patients.Although the exact pathogenesis of HE has not yet been fully elucidated,recent advances have improved our understanding of its pathophysiology,leading to evolving therapeutic strategies.This review summarizes the mechanisms underlying HE and the latest progress in its treatment,aiming to enhance the knowledge and improve diagnosis and therapy.

Objective:To compare the efficacy of oliceridine and sufentanil when combined with propofol for painless gastroscopy.Methods:In this randomized controlled trial, 66 patients of either sex, aged 18-64 yr, with a body mass index of 18-26 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective painless gastroscopy from September 2024 to November 2024, were divided into 2 groups ( n=33 each) using a table of computer-generated random numbers: sufentanil combined with propofol group (SP group) and oliceridine combined with propofol group (OP group). Sufentanil 0.1 μg/kg was intravenously injected in group SP, oliceridine 0.02 mg/kg was intravenously injected in group OP, and 1 min later propofol 2 mg/kg was intravenously injected in both groups. When the modified Observer′s Assessment of Alertness and Sedation score ≤ 1, the painless gastroscopy was performed. Heart rate, mean arterial pressure and peripheral oxygen saturation were recorded on admission to the operating room, immediately after insertion of the gastroscope, and at the end of procedure. The success of sedation, time of gastroscopy, emergence time, consumption of propofol and use of vasoactive drugs were recorded. The occurrence of adverse events such as respiratory depression, hypotension, dizziness and nausea was also recorded. Results:Compared with group SP, the incidence of respiratory depression was significantly decreased in group OP ( P<0.05). There was no statistically significant difference in the incidence of hypotension, dizziness and nausea and heart rate, mean arterial pressure and peripheral oxygen saturation at different time points between the two groups ( P>0.05). Conclusions:Oliceridine provides better efficacy than sufentanil when combined with propofol in painless gastroscopy.

Objective To analyze the clinical characteristics of cancer related anemia(CRA)in older cancer patients undergoing multi-line anti-tumor treatment.Methods A cross-sectional study was conducted,including patients with CRA who were≥65 years old and had received or were currently undergoing multi-line treatment at 9 hospitals in Beijing from June 1,2018 to September 30,2023.Data on gender,age,past history,family history,tumor type,metastasis site,clinical symptoms,blood routine,specialized examination for anemia,anti-tumor and anemia correction treatment were collected.The basic characteristics of the included patients,clinical symptoms,the status of blood cell reduction,treatment conditions,and the distribution of traditional Chinese medicine(TCM)syndrome characteristics were analyzed.Results A total of 602 patients were included.The tumor types included lung cancer,colorectal cancer,gastric cancer,esophageal cancer,breast cancer,gynecological tumors,lymphoma.The overall median hemoglobin(HGB)level was 99.00(88.00,107.00)g/L.The HGB levels of patients with different tumor types showed significant differences(P<0.001).The HGB levels of patients with gynecological tumors were significantly lower than those of patients with colorectal cancer,lung cancer and esophageal cancer(P<0.05).The most common clinical symptoms were fatigue,loss of appetite,irregular bowel movements and pain.In terms of anti-tumor treatment,405 patients were receiving multi-line anti-tumor treatment(including combined chemotherapy,combined radiotherapy,combined targeted therapy,and combined immunotherapy),197 patients were receiving symptomatic supportive treatment after multi-line anti-tumor treatment.In terms of anemia correction treatment,183 patients received erythropoietin,folic acid,iron,vitamin B12,or blood transfusion,while 293 patients received TCM for correcting anemia(including Chinese patent medicines,Chinese herbal decoctions,combinations of Chinese patent medicines and Chinese herbal decoctions).Specialized tests for anemia,such as serum iron,total iron binding capacity,transferrin saturation,transferrin,erythropoietin et al,have a detection rate of only 3.65%～27.91%.In terms of the characteristics of TCM syndromes,the main TCM syndrome types of the patients were as follows:syndrome of spleen-stomach weakness,syndrome of qi and blood deficiency,syndrome of heart-spleen deficiency,syndrome of spleen-kidney yang deficiency,syndrome of liver and kidney yin deficiency.Some patients also have the accompanying symptoms of internal binding of static blood and poison,phlegm dampness retention.Further comparison revealed that the HGB level of older patients with CRA who had syndrome of spleen-stomach weakness was significantly lower than patients with other symptom types(P<0.001).The HGB level of patients with syndrome of qi and blood deficiency was significantly lower than patients with syndrome of spleen-kidney yang deficiency(P<0.01)and syndrome of liver and kidney yin deficiency(P<0.001).Patients with symptoms of internal binding of static blood and poison,or symptoms of phlegm dampness retention had significantly lower HGB levels compared to those without accompanying symptoms(P<0.01).Conclusion The rate of specialized blood test for anemia in older patients with CRA was relatively low.The most common TCM syndrome types were syndrome of spleen-stomach weakness and syndrome of qi and blood deficiency.The overall treatment rate was also low.The screening,specialized diagnosis and monitoring of older patients with CRA need to be given more attention,and treatment methods such as TCM,Western medicine,and integrated TCM-Western medicine should be selected based on the patient's condition.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To analyze the current management status of real-world studies (RWS) in the medical institutions in China and suggest improvement focus for the management optimization.Methods:Surveys were conducted in 81 medical institutions nationwide. Convenience sampling was used to recruit survey subjects, and data were collected through self-administered questionnaires, followed by statistical analysis using descriptive methods.Results:The survey results indicated that 92.6% (75/81) of the medical institutions surveyed had undertaken RWS projects, with electronic medical records being the primary data source (89.3%, 67/75). Retrospective and prospective observational studies were the main types of study designs. Additionally, 96.3% (78/81) of the research subjects indicated that their medical institution expressed willingness to participate in or undertake RWS projects in the future. In terms of management, all types of RWS projects were managed by clinical trial center (24.0, 18/75), but differences existed in the management practices among medical institutions. Moreover, the challenges in data quality and standardization, study design and staff training, data and privacy protection and information technology support appeared in the management of RWS projects.Conclusions:It suggests to optimize the management processes of RWS projects in medical institutions and improve relevant laws and regulations to promote the development of RWS in China.

Objective:To compare the efficacy of oliceridine and sufentanil when combined with propofol for painless gastroscopy.Methods:In this randomized controlled trial, 66 patients of either sex, aged 18-64 yr, with a body mass index of 18-26 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective painless gastroscopy from September 2024 to November 2024, were divided into 2 groups ( n=33 each) using a table of computer-generated random numbers: sufentanil combined with propofol group (SP group) and oliceridine combined with propofol group (OP group). Sufentanil 0.1 μg/kg was intravenously injected in group SP, oliceridine 0.02 mg/kg was intravenously injected in group OP, and 1 min later propofol 2 mg/kg was intravenously injected in both groups. When the modified Observer′s Assessment of Alertness and Sedation score ≤ 1, the painless gastroscopy was performed. Heart rate, mean arterial pressure and peripheral oxygen saturation were recorded on admission to the operating room, immediately after insertion of the gastroscope, and at the end of procedure. The success of sedation, time of gastroscopy, emergence time, consumption of propofol and use of vasoactive drugs were recorded. The occurrence of adverse events such as respiratory depression, hypotension, dizziness and nausea was also recorded. Results:Compared with group SP, the incidence of respiratory depression was significantly decreased in group OP ( P<0.05). There was no statistically significant difference in the incidence of hypotension, dizziness and nausea and heart rate, mean arterial pressure and peripheral oxygen saturation at different time points between the two groups ( P>0.05). Conclusions:Oliceridine provides better efficacy than sufentanil when combined with propofol in painless gastroscopy.

This study aims to investigate the characteristics of chitosan-loaded miR-146a nanoparti-cles and explore their protective effect against acute liver cell injury induced by LPS in vitro.Galac-tosylated arginine chitosan(GCA)nanoparticles were successfully synthesized,prepared and used to further prepare GCA-miR-146a nanoparticles with different mass ratios by ion cross-linking method.The binding efficiency of miR-146a by GCA nanoparticles was detected by gel retardation experiment.Particle size,morphology and potential were observed and detected by transmission e-lectron microscopy and Zetasizer NanoZS90 respectively.The cytotoxicity of GCA nanoparticles on HepG2 cells was detected by CCK-8 kit.Cellular uptake was assayed by fluorescence microscopy to select the optimum ratio for the further study.The LPS induced acute liver cell injury were evalua-ted by real-time fluorescence quantitative PCR.The results showed that the mass ratio of GCA-miR-146a was 5∶1.Encapsulation efficiency and drug loading efficiency of the nanoparticles reached 97.11％and 20.08％,respectively.The 100 nm nanoparticles with 1.15 mV surface charge showed uniform morphology.The GCA-miR-146a nanoparticles had no cytotoxicity and had high transfection efficiency on HepG2 cells.The study demonstrated that GCA-miR-146 ananoparticles could significantly increase the expression of miR-146a in HepG2 cells and reduce the mRNA ex-pression levels of IL-6 and TNF-α in vitro.The prepared GCA nanoparticles loaded with miR-146a had high loading efficiency and could protect LPS-induced acute liver cell injury in vitro.