This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Tumors continue to be a major challenge in human survival that we have yet to overcome. Despite the variety of treatment options available, we have not yet found an effective method. As more and more research is conducted, attention has been turned to a new field for tumor treatment—the tumor microenvironment (TME). This is a dynamic and complex environment consisting of various matrix cells surrounding cancer cells, including surrounding immune cells, blood vessels, extracellular matrix, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules, and some specific cell types. Firstly, endothelial cells play a key role in tumor development and the immune system’s protection of tumor cells. Secondly, immune cells, such as macrophages, Treg cells, Th17 cells, are widely involved in various immune responses and activities in the human body, such as inflammation responses promoting survival carefully orchestrated by the tumor. Even though many studies have extensively researched the TME and found many research schemes, so far, no key effective method has been found to treat tumors by affecting the TME. The TME is a key interaction area between the host immune system and the tumor. Cells within the TME influence each other and interact with cancer cells to affect cancer cell invasion, tumor growth, and metastasis. This is a new direction for cancer treatment. In the complex environment of the TME, post-translational modifications (PTMs) of proteins have been proven to play an important role in the TME. PTMs are dynamic, strictly regulated changes to proteins that control their function by regulating their structure, spatial location, and interaction. Among PTMs, a reversible post-translational modification called SUMOylation is a common regulatory mechanism in cellular processes. It is a post-translational modification that targets lysine residues with a small ubiquitin-like modifier (SUMO) in a reversible post-translational modification manner. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis, and apoptosis, playing a pivotal role in the TME, such as DNA damage repair, tumor metastasis, and also participates in immune cell differentiation, activation, and inhibition of immune cells. On the other hand, SUMO or sentrin-specific protease (SENP) inhibitors can interfere with the SUMOylation process, thereby affecting many biological processes, including immune response, carcinogenesis, cell cycle progression, and cell apoptosis, etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.

【Objective】 To study the molecular mechanism of 95 samples of serological ABO subtypes. 【Methods】 A total of 95 samples with discrepancy between forward and reverse blood grouping were subjected to serological confirmation, and genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP). For those subtype alleles could not be detected by PCR-SSP, ABO gene exon 1-7 sequencing and gene single strand sequencing were performed successively to determine the mutation site and the gene location. 【Results】 A total of 34 ABO alleles were detected in 95 samples. Five common ABO alleles (ABO^*A1.01, ABO^*A1.02, ABO^*B.01, ABO^*O.01.01 and ABO^*O.01.02) and 29 rare ABO alleles were identified, including 16 named alleles by ISBT (ABO^*A2.01, ABO^*A2.05, ABO^*A2.13, ABO^*A3.07, ABO^*AW.37, ABO^*AEL.05, ABO^*B3.01, ABO^*B3.05, ABO^*BW.03, ABO^*BW.07, ABO^*BW.27, ABO^*BEL.03, ABO^*cisAB.01, ABO^*cisAB.05, ABO^*BA.02, ABO^*BA.04) and 5 named alleles by dbRBC(A223, B309, Bw37, Bel09, Bw40)and eight unnamed alleles [ABO^*B.01+ 978C>A, ABO^*A1.02+ 248A>T, ABO^*B.01+ 125dupT, ABO^*B.01+ (98+ 1G>A), ABO^*A1.02/ABO^*B.01+ 1A>G, ABO^*A1.02/ABO^*O.01.01+ 28G>T, ABO^*A1.02/ABO^*B.01+ 538C>T, ABO^*A1.02/ABO^*O.01.01+ 797insT] .The last four samples could not be verified by single strand because of insufficient samples. In 95 samples, 76 samples (21 named alleles of ISBT and dbRBC) were identified by PCR-SSP, and the remaining 19 samples were identified by exon 1-7 sequencing of ABO gene, of which 8 were identified as unnamed alleles, and the remaining 11 samples were not identified as subtype alleles. 【Conclusion】 The molecular genetic mechanism of 95 serological ABO subtypes was revealed, and 8 rare novel alleles were identified. The detection of ambiguous blood groups is influenced by factors such as patient pathology and physiology, therefore the combination of serological testing and genetic testing is suggested for the identification of ABO subtype.

Objective:Quantitative analysis of policies on equalization of basic public health services was used,to comprehensive understanding of characteristics and the use of combinations of policy tools,and to provide recommendations for promoting equalization of basic public health services in China.Methods:The research object was policies on equalization of basic public health services by the central government from 2009 to 2022,and a three-dimensional policy analysis framework of"Policy tools(dimension X)-Stakeholders(dimension Y)-Policy process(dimension Z)"was constructed to carry out the content analysis of policies.Results:The proportion of supply-oriented policy tools was reasonable,and policy focus on government departments and policy implementation stage;Public health programs have been mainly used,and capacity enhancement of primary health care institutions has been valued and given financial and human resources support.However,there were structural dysfunction,imbalance in policy patterns of interest subjects,and uneven attention at policy stages.Suggestions:Promote the optimization of internal structure of policy tools,diversify policy attention to stakeholders,and rationalize distribute policy phases.

This study aims to investigate the role and specific mechanisms of HO1 in mitigating lung inflammation after RSV infection.An RSV-infected mouse model was established,and lung tissues were collected for RNA-seq and differential gene expression analysis.HE staining and BALF cell counting were used to observe inflammation in the mouse lung tissues.Changes in HO1 expression were detected through immunohistochemistry,Western blotting,and qRT-PCR;inflammatory cytokine levels were assessed using qRT-PCR.HEMIN target proteins were predicted and analyzed by underwent GO and KEGG enrichment test;ROS levels in alveolar epithelial cells were measured using flow cytometry and immunofluorescence.Lysosomal changes were observed using transmission electron microscopy.The results demonstrated that HO1 expression was upregulated in the lung tissues of RSV-infected mice.Inducing HO1 expression alleviated lung tissue pathology,and lowered inflammatory cytokines IL-6 and TNF-α levels.RSV infection promoted ROS release and accumulation in lung epithelial cells,leading to an increase in autolysosomes.The induction of HO1 expression facilitated ROS clearance and reduced the number of autolysosomes.Therefore,the protective effect of HO 1 against oxidative stress reduces intracellular ROS generation,maintains organelle homeostasis,and reducing inflammatory cytokine IL-6,IL-8 and CXCL-10 levels.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

Background: The purpose of this study was to examine the radiographic and clinical outcomes of stemless reverse total shoulder arthroplasty (RTSA) after a minimum 2-year follow-up. Methods: Between July 2018 and March 2023, 50 patients underwent 50 stemless RTSA with the Lima component. Twenty-eight patients with a follow-up of more than 2 years were reviewed. The average age was 71.9 years (range, 61–85 years), and the average follow-up period was 2.2 years (range, 2.0–5.1 years). Bone marrow density of the proximal humerus was measured before RTSA. We evaluated preoperative and postoperative range of motion, clinical score, radiographic change, and postoperative complications. Results: Significant increases were observed postoperatively in forward flexion (112.0°–162.5°, P<0.01) and internal rotation (from L3 to T12 level, P<0.05). No changes were observed in external rotation (from 43.0° to 45.2°, P=0.762). The clinical scores improved for Korean Shoulder Scoring system (from 64 to 93, P<0.01) and American Shoulder and Elbow Surgeons score (from 17.5 to 27.3, P<0.01). Although radiolucent lines of less than 2 mm were observed in all cases, no osteolysis and loosening of the stemless humeral component was found. Scapular notching was observed in 18 cases (64.3%). Conclusions Stemless RTSA showed good radiographic and clinical results after a minimum 2-year follow-up.Level of evidence: IV.

Background: The purpose of this study was to examine the radiographic and clinical outcomes of stemless reverse total shoulder arthroplasty (RTSA) after a minimum 2-year follow-up. Methods: Between July 2018 and March 2023, 50 patients underwent 50 stemless RTSA with the Lima component. Twenty-eight patients with a follow-up of more than 2 years were reviewed. The average age was 71.9 years (range, 61–85 years), and the average follow-up period was 2.2 years (range, 2.0–5.1 years). Bone marrow density of the proximal humerus was measured before RTSA. We evaluated preoperative and postoperative range of motion, clinical score, radiographic change, and postoperative complications. Results: Significant increases were observed postoperatively in forward flexion (112.0°–162.5°, P<0.01) and internal rotation (from L3 to T12 level, P<0.05). No changes were observed in external rotation (from 43.0° to 45.2°, P=0.762). The clinical scores improved for Korean Shoulder Scoring system (from 64 to 93, P<0.01) and American Shoulder and Elbow Surgeons score (from 17.5 to 27.3, P<0.01). Although radiolucent lines of less than 2 mm were observed in all cases, no osteolysis and loosening of the stemless humeral component was found. Scapular notching was observed in 18 cases (64.3%). Conclusions Stemless RTSA showed good radiographic and clinical results after a minimum 2-year follow-up.Level of evidence: IV.

Background: The purpose of this study was to examine the radiographic and clinical outcomes of stemless reverse total shoulder arthroplasty (RTSA) after a minimum 2-year follow-up. Methods: Between July 2018 and March 2023, 50 patients underwent 50 stemless RTSA with the Lima component. Twenty-eight patients with a follow-up of more than 2 years were reviewed. The average age was 71.9 years (range, 61–85 years), and the average follow-up period was 2.2 years (range, 2.0–5.1 years). Bone marrow density of the proximal humerus was measured before RTSA. We evaluated preoperative and postoperative range of motion, clinical score, radiographic change, and postoperative complications. Results: Significant increases were observed postoperatively in forward flexion (112.0°–162.5°, P<0.01) and internal rotation (from L3 to T12 level, P<0.05). No changes were observed in external rotation (from 43.0° to 45.2°, P=0.762). The clinical scores improved for Korean Shoulder Scoring system (from 64 to 93, P<0.01) and American Shoulder and Elbow Surgeons score (from 17.5 to 27.3, P<0.01). Although radiolucent lines of less than 2 mm were observed in all cases, no osteolysis and loosening of the stemless humeral component was found. Scapular notching was observed in 18 cases (64.3%). Conclusions Stemless RTSA showed good radiographic and clinical results after a minimum 2-year follow-up.Level of evidence: IV.