Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Objective To investigate the mortality and risk factors of HIV-infected patients complicated with progressive multifocal leukoencephalopathy(PML)to inform the outcomes of these patients.Methods The clinical data of people living with HIV related PML who were treated at Chongqing Public Health Medical Treatment Center from January 1,2019 to December 31,2023 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.Log-rank test was performed.Cox regression model was used for multivariate analysis.Results A total of 42 people living with HIV related PML were enrolled,including 34 males(81.0％).The median age was 44.5(36.3,51.0)years.PML was confirmed in 76.2％(32/42)of patients,and possible PML was diagnosed in 23.8％(10/42)of patients.The median time to diagnosis was 32.5(14.8,58.3)days.The median CD4+T cell count was 69.0(39.8,112.0)cells/μL.The median HIV viral load was 5.05(2.62,5.77)log10 copies/mL.The overall mortality rate was 54.8％(23/42)for patients with HIV related PML.CD4+T cell count ≤50 cells/μL and initial modified Rankin scale(mRS)score ≥4 points were independent risk factors for the overall mortality of people living with HIV related PML(P＜0.05).Conclusions People living with HIV related PML have a high mortality rate.Low CD4+T cell count and high initial mRS score were independent risk factors for the mortality of patients with HIV related PML.Currently,no definitive and effective drug treatment is available for PML.Early detection,diagnosis and initiation of antiretroviral therapy may improve the outcomes of patients.

Objective:To investigate the impact of metformin on the Beh?et's disease (BD) mice model via the Treg/Th17 axis.Methods:The BD mice model was established by subcutaneous injection of HSV-1. Four groups were established, including healthy control group, model group, high-dose metformin group, and low-dose metformin group. The HSV-1 DNA copy number in the peripheral blood was measured using qRT-PCR. Plasma levels of TGF-β 1, IL-10, IL-17, IL-23, IL-6, and TNF-α were assessed by ELISA. Flow cytometry was employed to determine the proportion of Treg and Th17 cells in the spleen. One-way analysis of variance was used for inter-group comparisons, pairwise comparisons were performed using SNK- q test. Results:Thirty-eight BD models were successfully established, with 28 survived. Compared to the BD model group, the metformin treatment groups showed faster healing of genital ulcers, joint redness/swelling, and skin ulcers, along with better mental status. HSV-1 copy numbers decreased in the metformin groups compared to the model group at 20 and 30 days post-treatment. Compared to the healthy control group, the model group exhibited elevated levels of TGF-β 1, IL-17, IL-6, IL-23, and TNF-α, but a decrease in IL-10. Following high-dose metformin treatment, TGF-β 1, IL-17, IL-6, IL-23, and TNF-α were significantly reduced ( q=16.17, P<0.001; q=8.76, P<0.001; q=6.78, P=0.004; q=4.45, P=0.020; q=12.08, P<0.001), accompanied by elevated IL-10 (specific value) ( q=6.28, P<0.001). Compared with the control group [Treg: (1.82±0.68)%; Th17: (2.12±0.86)%], the model group showed significantly elevated proportions of Treg cells[(6.03±2.42)%] ( q=5.01, P<0.001) and Th17 cell [(3.40±0.58)%] ( q=2.96, P=0.017). After high-dose metformin treatment, both Treg cell proportion [(3.20±1.66)%] and Th17 cell proportion [(2.16±0.78)%] decreased compared to the model group ( q=3.05, P=0.014). No significant differences were observed between the high-and low-dose metformin groups across all measured indicators, indicating similar efficacy. Conclusion:Metformin could reduce HSV-1 virus replication, reduce the levels of inflammatory cytokines and regulate Treg/Th17 axis to alleviate the BD symptoms. This study provides evidence for repurposing metformin in the treatment of Beh?et's disease.

Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.

Objective:To evaluate the effectiveness and safety of zoledronic acid in patients with Paget′s disease of bone based on clinical data from a single medical center.Methods:This retrospective study included 24 patients diagnosed with Paget′s disease of bone and treated with zoledronic acid at Peking Union Medical College Hospital between January 2009 and June 2020. Demographic data, clinical symptoms, treatment efficacy, and safety outcomes were collected. The primary efficacy measure was serum alkaline phosphatase(ALP) levels. Treatment was considered effective if ALP levels returned to normal or decreased by more than 75% from baseline in the difference between the ALP level and its normal median value.Results:Among the 24 patients with Paget′s bone disease, the most commonly affected site was the skull(in 17 cases). All patients received a single 5 mg intravenous infusion of zoledronic acid. Serum ALP levels significantly decreased after treatment. Among the 15 patients who completed at least 3 months of follow-up, all achieved treatment success. The median time for serum ALP levels to reach the target was 13.1(9.4, 26.1) weeks. In 12 patients, ALP levels normalized within a medium of 16.9(11.5, 37.3) weeks, and remained stable over a medium follow-up of 4.56(2.42, 5.71) years. The most common side effects were hypocalcemia(21 cases, 87.5%) and flu-like symptoms(17 cases, 70.8%). Seven patients had severe hypocalcemia(serum calcium<1.75 mmol/L), and they had higher baseline levels of ALP, calcium, and phosphorus compared to those with mild hypocalcemia.Conclusions:Zoledronic acid 5 mg intravenous infusion effectively controlled disease activity in patients with Paget′s disease of bone. Generally, Most patients achieved treatment goals within 3-4 months, with sustained remission for a median of 4 years. Hypocalcemia was the most frequent side effect, underscoring the importance of timely calcium and vitamin D supplementation.

Objective To explore the pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks

Purpose To evaluate the diagnostic value of 18F-fluorodeoxyglucose(18F-FDG)PET/CT in differentiating primary lung cancer(PLC)from metastatic pulmonary breast cancer in breast cancer patients with solitary pulmonary lesion(SPL).Materials and Methods This retrospective analysis included 58 breast cancer patients with SPL in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2015 to August 2024.All patients had pathologically confirmed breast cancer with SPL and underwent PET/CT scans,including 36 cases of PLC and 22 cases of metastatic pulmonary breast cancer.Differences in clinical pathological features,high resolution CT morphological,and PET metabolic characteristics were analyzed.Multivariate Logistic regression was utilized to investigate independent predictive factors for SPL diagnosis.Results Statistically significant differences were observed between lesion density,nodule-lung interface,bubble sign,vascular convergence sign and pleural indentation sign(χ2=9.420,7.000,8.487,all P<0.05).PET/CT metabolic analysis revealed a significant difference in maximum standardized uptake value(SUVmax)between the two groups(Z=4.613,P<0.001).Multivariate analysis showed that bubble sign,pleural indentation sign and lower SUVmax were independent predictors for PLC.With an SUVmax threshold of 2.5,the area under the receiver operating curve(AUC)was 0.862,with a sensitivity of 90.9%,specificity of 77.8%and an accuracy of 82.8%.Combined analysis of high resolution CT and SUVmax demonstrated the highest diagnostic efficacy,with an area under the curve of 0.937,sensitivity of 90.9%,specificity of 94.4%and accuracy of 93.1%.Conclusion The presence of bubble sign,pleural indentation and SUVmax<2.5 suggests a high likelihood of PLC.Combined high resolution CT imaging features and PET metabolic characteristics significantly improve diagnostic accuracy for SPLs in breast cancer patients.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective:To investigate the causal relationship between plasma proteins and spontaneous abor-tion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS)data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finn-ish Genetic Research Project(FinnGen)as an outcome,the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR)study.The inverse variance weighting(IVW)method was used as the primary study method,with MR-Egger,weighted median and weighted mode complementing the results;and sensitivity analyses were performed using Cochrane's Q test,MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95％CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95％CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR0.905,95％CI 0.848-0.966,P=0.003)were associ-ated with a reduced risk of SA development,while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95％CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95％CI 1.008-1.071,P=0.012),dendritic cell-specif-ic intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95％CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95％CI 1.001-1.071,P=0.045)levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Co-chrane's Q test and MR-Egger intercept test,P＞0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mende-lian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion,which is potentially clinically valuable for studying the correlation between plasma proteins and spontane-ous abortion.

Non-alcoholic fatty liver disease(NAFLD)is characterized by excessive fat accumulation in the liver,which progresses to steatosis,inflammation and fibrosis with the progression of the disease,involving multiple cellular pathways and molecular mechanisms.Sterol regulatory element-binding proteins(SREBPs)have become key regulators of lipid metabolism in NAFLD,providing potential therapeutic targets for NAFLD.This article summarized molecular mechanism of SREBPs in NAFLD,and concluded the active components of Chinese materia medica targeted to regulate the SREBPs signaling pathway.It was found that the active components of Chinese materia medica(glycosides,flavonoids,polyphenols,polysaccharides,alkaloids,etc.)could inhibit the activation of SREBPs,inhibit de novo lipogenesis in the liver,and promote the β oxidation of free fatty acids and cholesterol metabolism,thus delaying or preventing the progress of NAFLD,which provided a reference for the treatment of NAFLD.