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.

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.

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.

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.

The left maxilla of a patient was resected because of tumor,and the defect was reconstruted with fibular transplantation.The autonomous dental implant robot technology was used to achieve precise implantation of multiple implants and immediate denture restoration within the limited left maxilla.The surgery was minimally invasive and efficient,and significantly reducing patient post-operative discomfort.The final restoration was completed 6 months after surgery.

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 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.