Objective To explore the infection status and clinical characteristics of human parvovirus B19 (HPV-B19) in patients with hematological disease. Methods A total of 94 patients with benign hematological disease, 128 patients with hematological malignancy, and 89 healthy individuals at Shanghai Eighth People’s Hospital from February 2019 to February 2020 were selected. The levels of specific IgM and nucleic acid of HPV-B19 in the plasma were detected using ELISA and PCR. The infection rates among the 3 groups and clinical characteristics between HPV-B19 positive and negative patients with hematological disease were compared. Results The positive rate of HPV-B19 IgM was 9.6% (9/94), the positive rate of nucleic acid was 11.7% (11/94), and the overall infection rate of HPV-B19 (IgM and/or nucleic acid positive) was 14.9% (14/94) in benign group of patients. The positive rate of HPV-B19 IgM was 18.0% (23/128), the positive rate of nucleic acid was 19.5% (25/128), and the overall infection rate of HPV-B19 was 26.6% (34/128) in malignant group of patients. The positive rate of HPV-B19 IgM was 1.1% (1/89), the positive rate of nucleic acid was 2.2% (2/89), and the overall infection rate of HPV-B19 was 2.2% (2/89) in healthy controls. The overall HPV-B19 infection rate in benign group of patients was higher than that in healthy controls (P＝0.006). The overall HPV-B19 infection rate was higher in malignant group of patients than that in benign group of patients (P＝0.037) and healthy controls (P＜0.001). In the benign group, the HPV-B19 infection rates in patients with pure red cell aplasia (PRCA), autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), and aplastic anemia (AA) were higher, with 44.4% (4/9), 27.3% (3/11), 25.0% (4/16), and 21.4% (3/14), respectively. In the malignant group, the HPV-B19 infection rates in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) were higher, with 42.9% (9/21) and 37.5% (6/16), respectively. The HPV-B19 positive patients in both hematological disease groups were older (P＜0.05). In patients with NHL, CLL or multiple myeloma (MM), HPV-B19 infection decreased the reticulocyte ratio (P＜0.05); in patients with NHL, acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), HPV-B19 infection prolonged bone marrow suppression time after chemotherapy (P＜0.05). Conclusions HPV-B19 infection rate in patients with hematological disease is elevated and HPV-B19 infection may influence the condition and treatment efficiency of these patients.

BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

To evaluate the immunogenicity and immunoprotective effects of a tRNA thiouridylase TgMnmA deletion strain of Toxoplasma gondii(T.gondii)on ICR mice,we constructed a mouse model immunized with RH△MnmA.Mice were immunized with 10 RH△MnmA tachyzoites by in-traperitoneal injection.After 30 d,indirect ELISA was used to detect the specific IgG antibody and its subtypes of immunized mice.Spleen lymphocyte suspension was prepared,and the splenic lym-phocyte subsets were analyzed by flow cytometry.Moreover,the relative expression level of cyto-kine mRNA was detected by real-time fluorescence quantitative PCR.After 30 d of immunization,mice were intraperitoneally inoculated with RH△ku80 tachyzoites.At 5 d post infection,the para-site load in the ascites,heart,liver and brain of mice was measured,and the survival of mice within 30 d after infection was observed and recorded.The results showed that compared with the control PBS group,RH△MnmA immunized group produced higher level of IgG and IgG2a antibodies,higher mRNA relative expression level of cytokines IL-2,IL-4,IL-6,IL-10,IL-12 and IFN-γ,and the number of CD4+and CD8a+in spleen lymphocytes also increased significantly.Mean-while,for the attack of RH△ku80 strain,the immune group can effectively reduce the parasite load in the ascites and some tissues,inhibit the reproduction of parasites In vivo,and significantly improve the survival rate of mice.The results of this study showed that the TgMnmA deletion strain of T.gondii can induce strong humoral and cellular immune responses in mice,and provide good immune protection against the infection of RHΔku80 strain,which has the potential to be-come a potentially promising live attenuated vaccine candidate against T.gondii.

OBJECTIVE To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.METHODS One hundred C57BL/6 mice were randomly divided into blank group,model group,Qingwen Baidu Drink low-dose group,Qingwen Baidu Drink medium-dose group,and Qingwen Baidu Drink high-dose group,with 20 mice in each group.HE staining was used to examine the pathological changes of lung tissues.ELISA was used to detect the expression levels of serum interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),chemokine ligand 10(CXCL10)and plasma coagulation factor Ⅲ(F3).qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1(MCP-1),cyclooxygenase-2(COX-2)and interferon-γ(IFN-γ)in lung tissues.The number of platelets(PLT)in plasma was analyzed by routine blood analysis instrument.Immunofluorescence a-nalysis was used to detect vascular endothelial cadherin(VE-cadherin),endothelial adhesion junction marker occludin 5(CLDN5)and pericyte marker neuronal collagen antigen 2(NG2)in alveolar capillary endothelial cells.Western blot was used to detect the pro-tein expression levels of cysteine-containing aspartate proteinase 11(Caspase11),GSDMD and GSDMD-N in mouse lung tissues.RESULTS Compared with the blank group,the lung tissue of the mice in the model group showed obvious pathological dam-age.The levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tis-sue were significantly increased(P<0.01),and the number of PLT and the content of F3 in plasma were significantly decreased(P<0.01).The fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissue was significantly enhanced(P<0.01),while the expression of Caspase11 and GSDMD-N proteins was increased(P<0.01).Compared with the model group,the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated,the levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tissue were significantly decreased(P<0.05,P<0.01),and the number of PLT and the content of F3 in plasma were increased(P<0.05,P<0.01);the fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissues was weakened(P<0.05,P<0.01),and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced(P<0.05,P<0.01).CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11,reduce the release of inflammatory factors,decrease blood loss and damage to vascular barrier function,and thus improve the lung injury caused by sepsis.

Objective:The impact of bystander CD8 + T cells (CD8 + Tbys) within the tumor microenvironment on the prognosis of early-stage non-small cell lung cancer (NSCLC) remains unclear, particularly concerning their infiltration differences at the invasive margin (IM) and tumor center (TC). Methods:We retrospectively collected postoperative specimens from 173 patients with primary early-stage NSCLC who underwent radical surgery at the Affiliated Tumor Hospital of Shandong First Medical University from 2014 to 2018. Tissue microarrays encompassing IM and TC regions were prepared and subjected to multicolor immunofluorescence staining (CK/CD8/CD103/DAPI). Image processing and phenotype recognition (CD8 + T cells, CK -CD8 +; CD8 + T bys, CK -CD8 +CD103 -) were performed using inFrom software, and automatic quantitative cell density analysis was conducted using R language. Differences in CD8 + T and CD8 + T bys densities at IM and TC were analyzed using the Mann-Whitney U test. The relationship between CD8 + T, CD8 + T bys and clinicopathological features was examined using the Kruskal-Wallis H test. The impact of CD8 + T and CD8 + T bys on recurrence-free survival (RFS) was evaluated using Kaplan-Meier, log-rank, and Cox proportional hazards models. Results:A total of 173 patients with stage ⅠA-ⅡA NSCLC were included, with a recurrence rate of 26.6% (46/173) and a median RFS of 62.3 months (range: 44.7-71.9 months). CD8 + T and CD8 + T bys densities (1/1 000) were significantly higher in the IM region than in the TC region [70(32, 155) vs. 37(18, 88), P＜0.001; 25(11, 46) vs. 18(7, 34), P=0.002]. No significant association was found between CD8 + T, CD8 + T bys and age, gender, smoking history, histological type, or pathological stage (all P＞0.05). Patients with low-density IM CD8 + T cells had lower RFS compared to those with high-density IM CD8 + T cells ( P=0.021; median RFS not reached), Further analysis revealed that patients with low-density IM CD8 + T bys cell had lower RFS compared to those with high-density IM CD8 + T bys ( P=0.047; median RFS not reached), and low-density IM CD8 + T cell was an independent risk factor for postoperative recurrence ( HR=1.836, 95% CI:1.007-3.347, P=0.048). Joint analysis of IM and TC revealed that patients with low IM CD8 + T bys and high TC CD8 + T bys had significantly lower RFS compared to the other three groups ( P=0.006), and this combination was an independent risk factor for postoperative recurrence in early-stage NSCLC ( HR=2.090, 95% CI:1.162-3.760, P=0.014). Conclusions:The spatial distribution of bystander CD8 + T cells within the primary tumor influences the prognosis of patients with early-stage NSCLC. Patients with low-density IM CD8 + T bys and high-density TC CD8 + T bys are more prone to recurrence after radical surgery.

This study innovatively incorporates on-site teaching with the International Museum of Stomatology into the curriculum to establish an immersive and intuitive teaching mode,promoting education from both theoretical and practical dimensions.The teaching effect is comprehensively evaluated to explore the pathway to optimization.Multi-dimensional questionnaires are designed to collect feedback data from students on teaching satisfaction,knowledge mastery,professional identity,and humanistic literacy perception,fol-lowed by in-depth quantitative and qualitative analyses.The results demonstrate that this teaching mode significantly enhances literacy,playing a critical role in helping stomatological students fully understand professional knowledge and humanistic connotations while sub-stantially improving their professional identity.This teaching mode gives a direction for innovative stomatological education,holds sig-nificant importance for cultivating stomatological professionals with both clinical skills and humanistic literacy,possessing substantial potential for promotion,application,and further refinement.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

Objective:To investigate the effect of cytoskeleton-associated protein 4 (CKAP4) gene knockout on maxillary expansion osteogenesis and its regulatory mechanism on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC).Methods:Nineteen wild type (WT) and nineteen CKAP4 gene knockout (Ckap4 -/-) mice aged 6-8 weeks were selected to establish a mouse model of rapid maxillary expansion. Samples were taken on the 7th and 14th day after the operation. Micro-CT and HE staining were used to evaluate bone regeneration. Tissue proteins in the modeled area were collected, and Western blotting analysis (WB) was used to detect the protein expression levels of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). BMSC were isolated from WT and Ckap4 -/- mice. The expression of surface markers CD29, Sca-1, CD44, CD45, CD34, and CD11b was detected by flow cytometry, and cell proliferation ability was detected by 5-ethynyl-2'-deoxyuridine (EdU). After 7 days of osteogenic induction, real-time fluorescence quantitative PCR (RT-qPCR) and WB were used to detect the expression levels of RUXN2, ALP, OCN, protein kinase B (AKT), and phosphorylated protein kinase B (p-AKT). After 21 days, alizarin red staining and cetyl pyridine chloride quantification were used to detect the differences in mineralized nodule formation in each group. In CKAP4 gene knockout BMSC, the small-molecule AKT agonist sc79 (4 μg/ml) was added as the intervention group (Ckap4 -/- +sc79), and dimethyl sulfoxide (DMSO) treatment was used as the control group (Ckap4 -/- +DMSO). After osteogenic induction, RT-qPCR, WB, and alizarin red staining were used to compare the osteogenic differentiation differences between the two groups of cells. Results:The micro-CT results showed that at 7 days and 14 days after surgery, the new bone volume in the Ckap4 -/- group [(0.070±0.010) and (0.146±0.019) mm 3] was significantly lower than that in the WT group [(0.094±0.006) and (0.196±0.013) mm 3] (both P<0.01). HE-stained histological sections showed that the area of new bone tissue in the Ckap4 -/- group at 7 days and 14 days after surgery [(0.101±0.008) and (0.158±0.010) mm 2] was also significantly lower than that in the WT group [(0.116±0.005) and (0.183±0.008) mm 2] (both P<0.05). WB was used to detect the tissue proteins in the maxillary modeling area of mice in the two groups 7 days after surgery. The results showed that the expression levels of ALP, RUNX2 and OCN in the Ckap4 -/- group were significantly lower than those in the WT group. BMSC from wild-type mice and CKAP4 knockout mice were both positively expressed for CD29, CD44, and Sca-1, and basically not expressed for CD45, CD34, and CD11b. EdU assay showed that there was no significant difference in the proliferation ability of cells in the two groups. After 21 days of osteogenic induction of BMSC, alizarin red staining results showed that the number of mineralized nodules in the Ckap4 -/- group was significantly less than that in the WT group. After adding sc79, the number of mineralized nodules increased significantly, which was consistent with the results of cetyl pyridine chloride quantification. After 7 days of osteogenic induction, It was found that the expression levels of ALP, RUNX2, and OCN in the CKAP4 -/-group (0.751±0.066, 0.484±0.040, 0.679±0.063) were significantly lower than those in the WT group (1.000±0.113, 1.000±0.081, 1.000±0.113) (all P<0.001). The results of WB were consistent with those of RT-qPCR. At the same time, the WB results showed that the level of p-AKT protein in the CKAP4 -/-group (0.518±0.114) was significantly lower than that in the WT group (1.000±0.234) ( P<0.05). After treatment with sc79 for 7 days of osteogenic induction, RT-qPCR was used to detect the gene expression levels of ALP, RUNX2, and OCN. The results showed that the expression levels in the CKAP4 -/-+sc79 group (2.755±0.353, 4.800±0.990, 2.524±0.137) were significantly higher than those in the CKAP4 -/-+DMSO group (1.000±0.078, 1.000±0.247, 1.000±0.175) (all P<0.001). Conclusions:CKAP4 knockout inhibits the osteogenic differentiation of BMSC by reducing the activity of the PI3K/AKT signaling pathway, thereby suppressing osteogenesis in maxillary expansion.

Objective:To systematically evaluate the efficacy, patient-reported outcomes (PROs) and safety of hyaluronic acid (HA) fillers and collagen stimulators (PCL/PLLA) for various facial aesthetic indications.Methods:This study focused on facial fillers approved and widely used in China, including HA fillers such as Juvéderm?, Restylane?, Belotero?, Fillmed?, and PCL/PLLA such as Ellansé?, L?viselle?, and CureWhite?. A systematic literature search was conducted across both English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, and Wanfang Data, covering the period from database inception to August 24, 2023, to identify randomized controlled trials (RCTs). The characteristics and outcomes of the included RCTs were summarized and analyzed, including efficacy indicators by injection site, patient satisfaction, and safety profiles. Network meta-analysis (NMA) was performed using R software to compare efficacy outcomes, including the 6-month improvement response rate for nasolabial folds (NLF) and the global aesthetic improvement scale (GAIS).Results:A total of 38 articles were included. Among them, Juvéderm? was most frequently used as the treatment group (17 out of 38 articles), while Restylane? was the most common comparator (17 out of 38 articles), particularly in studies involving NLF injections (15 out of 16 articles). For collagen stimulators, only 2 studies on Ellansé? were included, both focusing solely on NLF treatment. Quality assessment showed that 34 studies were of medium to high quality, with Juvéderm? accounting for the majority of high-quality studies (11 articles). Based on injection sites, NLF was the most studied area (16 articles), followed by the midface (8 articles), and the remaining 14 articles covered other regions including lips, nose, chin, and infraorbital area. In the NLF region, the 6-month improvement response rate assessed by blinded investigators showed that Juvéderm? showed better outcomes than Restylane? ( RR=1.07, 95% CI: 0.89-1.32), while Belotero? was slightly inferior to Restylane? ( RR=0.97, 95% CI: 0.65-1.44), although the differences were not statistically significant. Subject-reported outcomes showed consistent trends with investigator assessments. For 6-month GAIS improvement, Juvéderm? and Restylane? showed comparable result within the HA filler category ( RR=1.01, 95% CI: 0.71-1.43). The collagen stimulator Ellansé? demonstrated numerically higher values than HA fillers ( RR=1.32, 95% CI: 0.86-2.08). However, none of these differences reached statistical significance. In midface treatments, Juvéderm? had more long-term evidence, with follow-up periods extending up to 24 months. Four studies reported numerically greater volume enhancement with Juvéderm? compared to Restylane?. For other facial areas, Juvéderm? had the most comprehensive clinical evidence, covering the widest range of injection sites. No relevant RCTs were available for collagen stimulators in these regions. Regarding patient satisfaction, 19 studies reported patient-reported outcomes, with Juvéderm? contributing 16 of them, and showing higher satisfaction in 6 head-to-head comparisons with Restylane?. In contrast, collagen stimulators currently lack such evidence. Safety result indicated that HA fillers were generally safe and well tolerated, while safety data for collagen stimulators remain limited due to insufficient high-quality evidence. Conclusion:Among the HA fillers, Juvéderm? has a large quantity and highest quality of clinical studies, and NMA result shows its superior efficacy in NLF. In comparison, the current evidence is still not sufficient to draw a clear conclusion for the PCL/PLLA due to a lack of adequate high-quality clinical evidence regarding its clinical efficacy, PROs, and safety.