Objective: To establish evidence-based, safe and efficient management of HIV-reactive blood donors by investigating safe and feasible assessment strategies for HIV-reactive blood donors based on routine blood screening data. Methods: The data of blood screening, supplementary testing, follow-up and CDC confirmation for HIV-reactive blood donors in our center from 2014 to 2024 were analyzed systematically to confirm HIV infection and identify infection status. Results: There were 1 235 samples (0.13%, 1 235/928 000) reactive in HIV blood screening over the 11-year period. A-mong them, 199 donors (16.11%) in asymptomatic HIV infection (HIV Ag/Ab++&HIV RNA+), 2(0.16%) as acute early HIV infection (HIV Ag/Ab+-&HIV RNA+) and 7(0.57%) as window-period infection (HIV RNA positive only) were confirmed. Donors with the result of HIV Ag/Ab+-&HIV RNA-(single-positive) were all excluded for HIV infection, while 1 in 6 HIV Ag/Ab++&HIV RNA-donors (double-positive) was confirmed to have HIV infection. When HIV Ag/Ab reagents were used continuously before and after the follow-up, it's observed in one reagent that the proportion of negative results in subsequent follow-up in single-positive donors who had negative results in the first sampling was significantly higher than the proportion of negative results in subsequent follow-up in those initially single-positive (P<0.05). But no significant difference was observed in another reagent (P>0.05). When reagents were changed in follow-up, the rate of singlepositive donors with negative results in the first sampling reached 96.7%, which was significantly higher than the negative rate of those without reagent changing in follow-up (P<0.05). Conclusion: Based on the serological and nucleic acid testing results of HIV blood screening, the confirmation of HIV infection and identification of infection status can be achieved accurately and efficiently. All HIV Ag/Ab+-&HIV RNA-donors were confirmed as false positive, and should be maintained their eligibilities for blood donation, but recommended to pass the retest before next donation. Using a different reagent for retesting helps improve the eligible rate. HIV Ag/Ab++&HIV RNA-donors should be deferred permanently due to the risk of true positivity.

Objective: To evaluate repeated testing on blood screening platforms in confirmation of non-discriminatory reactive (NDR) samples in nucleic acid testing (NAT). Methods: A total of 102 HBsAg-negative/NAT NDR samples were collected from voluntary blood donors at Dalian Blood Center between January 2021 and December 2023. Repeated testing was performed using two NAT platforms (Cobas s201 and Panther). For the first round of repeated testing, all samples were tested 12 times on each system; for the second round, the samples which were non-reactive or only reactive once in the first round were tested an additional 8 times. Anti-HBc and anti-HBs was detected using electrochemiluminescence assay (ECA). Meanwhile, blood donors were followed up. Results: The proportion of anti-HBc+ in 102 NDR samples was 88.2%. Forty-one samples (40.2%, 41/102) and 7 samples were confirmed HBV DNA+ in first-round and second-round repeated testing, respectively. The cumulative confirmation rate of HBV DNA+ was 47.1% (48/102) after repeated testing. Extra five blood donors detected HBV DNA+ in follow-up were identified as anti-HBc+ occult hepatitis B virus infection (OBI), while no window period infection was observed. Ultimately, there were 53 HBV infected donors confirmed, 46 HBV infection-unconfirmed, and 3 HBV uninfected. No significant difference was observed between the confirmation rate of the first-round testing and the cumulative confirmation rate after the second-round testing (P>0.05). The proportion of anti-HBc+ donors was quite high in both HBV infection-confirmed (98.1%) and unconfirmed group (82.6%), and donors with seronegative and anti-HBs-only occupied a high proportion in the latter (P<0.05). Conclusion: Numerous repeated testing of NDR samples using NAT platforms cannot achieve complete confirmation of HBV infection. Supplementary anti-HBc testing can minimize potential OBI risk among NDR donors, and is low-cost and efficient.

ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

Abstract The prevalence of hypertension in children and adolescents continues to rise with a trend toward earlier onset, presenting a phenomenon that cannot be fully explained by traditional risk factor frameworks. Circadian rhythm disruption, particularly the dual disturbance of dietary and sleep rhythms, has emerged as a novel risk factor and become a research hotspot. The review systematically summarizes the epidemiological associations, biological mechanisms, and intervention strategies regarding dietary rhythm, sleep rhythm, and their co exposure with blood pressure in children and adolescents. Future research needs to focus on Chinese pediatric populations through longitudinal cohort studies and randomized controlled trials to clarify causal relationships and regulatory mechanisms, thereby providing evidence based guidance for chronic disease prevention and control in children.

OBJECTIVE To compare the efficacy of ceftazidime and avibactam （CZA） monotherapy and combination therapy in the treatment of carbapenem-resistant Gram-negative bacteria （CRGNB） infections， and analyze the influencing factors. METHODS The data of patients with CRGNB infection who received CZA treatment from January 2020 to March 2025 were collected retrospectively. The patients were divided into the CZA monotherapy group （52 cases） and the CZA combination therapy group （85 cases） according to treatment regimen. The therapeutic effects of the two groups were compared， and the drug susceptibility results of isolated strains were recorded. The multivariate Logistic regression model was used to analyze the factors influencing clinical efficacy of CRGNB patients. RESULTS The bacterial clearance rate of patients was significantly higher in the CZA combination therapy group than in the CZA monotherapy group （P＝0.012）. However， when comparing the 30-day mortality rate and the clinical response rate between the two groups， no statistically significant differences were observed （P＞0.05）. Among the isolates， carbapenem-resistant Klebsiella pneumoniae had the highest sensitivity to tigecycline （87.3%） and carbapenem-resistant Pseudomonas aeruginosa showed 90.9% sensitivity to amikacin. Five isolates were resistant to CZA. The multivariate Logistic regression showed， lung infection， receiving continuous renal replacement therapy （CRRT）， and inadequate treatment courses were significantly correlated with clinical treatment failure （P＜0.05）. CONCLUSIONS For CRGNB infection， the clinical efficacy of CZA combination therapy is similar to that of monotherapy， but the combination therapy has a higher bacterial clearance rate. Lung infections， receiving CRRT and inadequate treatment courses （No. are independent risk factors for clinical treatment failure.

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

OBJECTIVE To evaluate the efficacy and safety of intranasal corticosteroids （INCS） combined with oral H1- antihistamine （AH） in the treatment of allergic rhinitis. METHODS A comprehensive literature search was conducted in PubMed， Embase， CNKI， and VIP database to collect randomized controlled trial （RCT） that INCS combined with AH （experimental group） versus INCS （control group） in the treatment of allergic rhinitis from the inception to December 31， 2024. After study selection， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 12 RCTs were included in the meta-analysis， with a total of 1 842 patients. Results of meta-analysis showed that， compared with the control group， patients in the experimental group had a greater reduction in sneezing scores， rhinorrhea scores， nasal congestion scores， nasal itching scores， total nasal symptom scores， total ocular symptom scores， and rhinoconjunctivitis quality of life questionnaire scores （P＜0.05）. The incidence of headache was lower in the experimental group （P＜0.05）； whereas there were no significant differences between the two groups in the incidence of nosebleed， dryness of the mouth and nose， drowsiness， fatigue， and total adverse events （P＞0.05）. CONCLUSIONS Compared with INCS monotherapy， the combination of INCS and oral AH provides superior efficacy and safety in the treatment of allergic rhinitis.

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male