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 explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Objective To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone(ROT)-induced Parkinson's disease(PD)model mouse.Methods SPF C57BL/6 mice were randomly divided into 6 groups,including control group,solvent control group,ROT model group,ACT001 5 mg/kg group(ROT+ACT001-5),ACT001 20 mg/kg group(ROT+ACT001-20),and levodopa(L-dopa)positive control group(ROT+L-dopa),with 9 mice in each group.The control group received an equivalent amount of intraperitoneal injection of saline,the solvent control group received an equivalent amount of rotenone solvent without rotenone,the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone.Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001,while the positive control group received levodopa intraperitoneally for 15 consecutive days.Behavioral changes in mice were assessed using open field,rotarod,pole-climbing,and balance beam tests.Immunofluorescence(IF)assay to detect the expression of tyrosine hydroxylase(TH)neurons,content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain;Real-time PCR was employed to measure the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in the substantia nigra of the mouse brain.Western blotting was used to measure the protein levels of TH,nuclear factor-κB(NF-κB)p65,NF-κB inhibitor α(IκBα),and phosphorylated IκBα(p-IκBα)in the substantia nigra of the mouse brain.Results Compared to the control group and the solvent control group,the rotenone-induced PD model group exhibited motor impairments in behavioral tests,a decrease in the number of TH positive neurons in the substantia nigra(P＜0.0001),decreased levels of TH-positive fibers in the striatum,activation of midbrain substantia microglia,and elevated levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 expression.ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice,increased the number of TH-positive neurons in the substantia nigra,increased levels of TH-positive fibers in the striatum,inhibition of microglial cell activation in the midbrain substantia nigra,and elevated the protein expression levels of IκBα while reducing the levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 in the substantia nigra(P＜0.05).At a dose of 5 mg/kg,ACT001 significantly improved behavioral impairments in rotenone-induced PD mice,reduced the loss of dopaminergic neurons,and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the suppression of inflammation.In summary,the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain,increased the number of TH-positive neurons,and augmented the population of dopaminergic neurons in the substantia nigra,exerting a protective effect on neurons.Conclusion ACT001 significantly improves behavioral deficits in ROT-induced PD mice,ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum,inhibits the activation of nigrostriatal microglia in the midbrain,and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.

Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Interleukin-8(IL-8)is an important biomarker of OSCC,and its level can reflect the occurrence and development of OSCC.It is of great significance to detect IL-8 rapidly and sensitively for the purpose of early diagnosis of OSCC.In this study,gold nanoparticles(AuNPs)with uniform particle size were synthesized by reduction of chloroauric acid with trisodium citrate,and the probe(AuNPs@mAb1)was prepared by coupling AuNPs with the murine anti-IL-8 monoclonal antibody mAb1.Cy5-NHS and murine anti-IL-8 monoclonal antibody mAb2 complex(Cy5-mAb2)and sheep anti-mouse IgG antibody were sprayed on nitrocellulose membrane to form test line(T line)and control line(C line)respectively,and reverse fluorescence-enhanced test strips were thus constructed,based on which an immunochromatographic method was established for highly sensitive detection of IL-8 in saliva samples.The experimental results showed that the test strip had good stability,high specificity and high sensitivity.The linear range for fluorescence detection of IL-8 was 0.01-100 ng/mL,and the limit of detection(3σ)was 7.93 pg/mL.The linear range for visualization detection was 6-100 ng/mL,with limit of detection(3σ)of 0.85 ng/mL.The fabricated test trip had good preparation reproducibility,with inter-and intra-batch assay precision of less than 5.5%.The test strip was used for detection of IL-8 in healthy human saliva samples,with spiked recoveries of 93.7% -102.4%,and relative standard deviations of 2.1% -4.3%.The fabricated test strip could be used for early screening of OSCC.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Phakic intraocular lens implantation has become one of the important means of correcting refractive errors today. Among them,the implantable collamer lens(ICL)is favored for its wide range of correction, excellent optical quality, and high safety, but the risks of postoperative complications such as glaucoma and anterior subcapsular opacification still exist. Vault is an important indicator for evaluating the safety after ICL implantation, and its ideal state is crucial for preventing complications. Studies have shown that iris morphology has a significant impact on vault. In order to further optimize surgical outcomes and improve surgical safety, this review comprehensively reviews the research progress of iris-related parameters in ICL implantation and discusses the importance of various parameters in preoperative evaluation and postoperative follow-up.

Objective:To explore the safety, economic benefits, and clinical application effect of the new practical patent open window central venous catheter combination dressing (Patent No.ZL 202121652858.8).Methods:From October 2022 to October 2023, a randomized controlled trial was conducted. A total of 120 tumor patients in Yunnan Cancer Hospital with indwelling central venous catheters who met the inclusion and exclusion criteria were randomly divided into three groups at a ratio of 1∶1∶1 with random digit table, with 40 patients in each group: control group 1, control group 2, and the experimental group. In control group 1, Smith & Nephew IV 3000 dressing was used, in control group 2, 3M transparent dressing was used; and in the experimental group, the self - developed fenestrated central venous catheter combined dressing by the researchers was used for catheter maintenance. The skin surface bacterial colonization, the occurrence of medical adhesive-related skin injuries, catheter maintenance time, and maintenance costs were compared among the three groups.Results:In control group 1, there were 21 males and 19 females, with an average age of (51.53 ± 12.01) years. In control group 2, there were 22 males and 18 females, with an average age of (54.00 ± 11.03) years. In the experimental group, there were 19 males and 21 females, with an average age of (53.60 ± 9.41) years. During the 72 - hour observation period, 1, 3, and 2 cases of bacterial colonization occurred in control group 1, control group 2, and the experimental group respectively, and there was no significant difference among the three groups ( χ2 = 1.10, P = 0.577). No medical adhesive - related skin injury occurred in the experimental group, and there was a significant difference compared with the 4 cases in control group 2 ( χ2 = 4.21, P = 0.040). The average catheter maintenance time and maintenance cost in the experimental group were (15.20 ± 1.56) minutes and (8.11 ± 1.35) yuan respectively. Compared with (21.05 ± 3.31) minutes and (13.16 ± 1.03) yuan in control group 1, the differences were statistically significant ( t = 5.85, 5.05, both P<0.001). Compared with (21.08 ± 3.00) minutes and (15.17 ± 1.63) yuan in control group 2, the differences were also statistically significant ( t = 5.88, 7.06, both P<0.001). Conclusions:The open-window central venous catheter combination dressing designed in this study can effectively reduce the incidence of medical adhesive-related skin injury, and also has a better role in saving maintenance time and reducing maintenance costs, especially for patients who need repeated dressing changes at the puncture point for treatment with the advantages of, convenience, economy, speed, firm fixation and safety.

Chronic spontaneous urticaria (CSU) is the most common phenotype of chronic urticaria. To date, second-generation H1 antihistamines (sgAHs) and omalizumab are the main treatment options for CSU. However, a considerable number of CSU patients are resistant to these therapies. Bruton's tyrosine kinase (BTK) inhibitors inhibit the degranulation of mast cells and basophils, as well as the production of antibodies by B cells, possessing a theoretical basis and potential benefits in the treatment of CSU. First-generation BTK inhibitors have been approved for the treatment of B cell-related malignancies, but there is a high risk of adverse reactions due to their poor selectivity. The second-generation BTK inhibitor remibrutinib has high affinity and selectivity for BTK, exhibiting good pharmacokinetic profiles. Phase Ⅱ and Ⅲ clinical trials of remibrutinib for CSU have been completed. Second-generation BTK inhibitors offer a novel treatment option for patients with CSU who do not respond adequately to increased doses of sgAHs. This review summarizes the mechanism of action, pharmacological characteristics, and clinical application of BTK inhibitors.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Objective To systematically evaluate the safety and efficacy of replacing tyrosine kinase inhibitors(TKIs)with similar drugs after they cause liver injury,based on case reports and case series studies.Methods PubMed,Embase,Cochrane,Web of Science,CNKI,Wanfang,and VIP databases were searched up to October 2023.Two reviewers independently screened the literature,extracted data,and assessed the quality of the studies.Descriptive and statistical analyses were performed.Results Twenty-six studies(22 case reports and 4 case series)were included,involving 75 patients who switched to similar drugs for TKI-induced liver injury,primarily targeting the epidermal growth factor receptor(EGFR),anaplastic lymphoma kinase(ALK),and multiple targets.The results indicate that majority of patients have favorable safety profiles after switching drugs,with normal liver function or no severe liver injury.Only one patient reported a serious liver adverse reaction,characterized by(grade 3 total bilirubin elevation).In terms of clinical efficacy,most patients responded well to the new TKIs,maintaining stable disease,or showing no progression during follow-up.Disease progression occurred in only two patients who switched from gefitinib to erlotinib after dose reduction due to non-hepatic adverse effects.Additionally,one patient who switched from erlotinib to afatinib experienced worsening tumor symptoms.Conclusion Evidence from published case reports and case series suggests that continuing treatment with similar drugs after TKI-induced liver injury,targeting EGFR,ALK,and multiple targets,demonstrates a certain degree of safety,efficacy,and clinical practicability.This can be a strategy after TKI discontinuation due to liver injury.However,there are no clear guidelines on drug selection,timing,and dosage,and further research is urgently needed.