Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95％CI:1.05～1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95％CI:1.02～1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.

Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95％CI:1.05～1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95％CI:1.02～1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

Objective To study the correlation between the serum ferritin level and the pathological classification,tumor stage,PD-L1 expression,disease control rate(DCR),and survival period of patients with lung cancer.Methods A total of 85 patients with lung cancer admitted to our hospital from February 2020 to February 2021 were selected as the research subjects.All patients received immunotherapy,and the serum ferritin levels of patients before and after immunotherapy were detected.Meanwhile,according to the difference in serum ferritin levels before and after immunotherapy,the patients were divided into the increased group(31 cases)and the decreased group(54 cases).The correlation between the serum ferritin level and the pathological classification,tumor stage and PD-L1 expression level of patients was analyzed,and the DCRs and survival periods of patients with serum ferritin level≥300 ng/mL and<300 ng/mL before treatment were compared,as well as the increased group and the decreased group.The survival curve of patients in each group was analyzed by the Kaplan-Meier.Results Patients with tumor stage Ⅰ to Ⅲ showed significantly lower serum ferritin levels than patients with tumor stage Ⅳ(P<0.05).The DCR,3-year survival rate and progression-free survival(PFS)of patients with serum ferritin level≥300 ng/mL were significantly lower/shorter than those of patients with serum ferritin level<300 ng/mL(P<0.05).The DCR,3-year survival rate and PFS of patients in the increased group were significantly lower/shorter than those in the decreased group(P<0.05).Conclusion The increased serum ferritin level in lung cancer patients before treatment and the further increase after treatment are significantly associated with the reduced efficacy of immunotherapy and the shortened survival period.The combination of baseline serum ferritin levels before treatment and dynamic changes after treatment may serve as a clinical biomarker panel for predicting immunotherapy outcomes.

Allergen-specific Immunotherapy (AIT) is currently the only allopathic treatment capable of modifying the natural course of immunoglobulin E (IgE)-mediated allergic diseases. Currently, there is a lack of recognized clinical markers for evaluating and predicting the efficacy of AIT, and some biological markers may have some potential for application. This article will summarize the currently known indicators for evaluating and predicting the therapeutic effects of AIT, with the aim of providing assistance in evaluating and monitoring the efficacy of AIT.

The prevalence of allergic diseases is on the rise,posing a significant global health challenge.Allergen specific immunotherapy(AIT)is the only treatment capable of altering the natural course of allergic diseases,offering long-term efficacy and the potential to prevent disease progression.However,its widespread application is hindered by factors such as lengthy treatment duration,adverse reactions,and patient compliance issues.In recent years,biologics targeting type 2 inflammatory pathways have played a crucial role at various stages of different allergic diseases.Research indicates that for patients with moderate to severe allergic diseases,using biologics during or prior to AIT can significantly enhance the safety of AIT,reduce the time required to reach maintenance doses,and markedly improve symptom scores.This article elucidates the synergistic mechanisms and recent advancements in the combined application of biologics and AIT in the treatment of allergic diseases.The aim is to provide a reference for the standardized treatment of allergic diseases.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To explore the clinical efficacy and safety of alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet in the treatment of postmenopausal osteoporosis(PMDP).Methods The patients with postmenopausal osteoporosis were divided into control group and treatment group according to the cohort method according to the treatment regimen.The control group was treated with calcium carbonate D3 tablet(600 mg,1 tablet a day)and alendronate sodium tablet(70 mg,once a week),while the treatment group was given injection of reacombinant teriparatide(200 U/20 μg,20 μg every day)on the basis of the control group.Both groups were continuously treated for 6 months.The clinical efficacy was compared after 6 months of treatment.The bone mineral density(BMD)of lumbar spine,total hip and femoral neck and levels of bone metabolism indicators[osteocalcin(OCN),tartrate-resistant acid phosphatase-5b(TRAP-5b),procollagen type Ⅰ amino-terminal propeptide(PINP),C-terminal cross-linked peptide of type Ⅰ collagen(CTX-Ⅰ)]before treatment and after 6 months of treatment and bone pain[visual analogue scale(VAS)]and quality of life[European Foundation Osteoporosis Quality of Life Questionnaire(ECOS-16)]before treatment and after 3 and 6 months of treatment were recorded,and the adverse drug reactions within 6 months of treatment were compared.Results Fifty-two cases in treatment group and 64 cases in control group were enrolled.After treatment,the total effective rates in treatment group and control group were 87.80％(36 cases/41 cases)and 68.29％(28 cases/41 cases),respectively(P＜0.05).The BMD values of lumbar spine in treatment group and control group after treatment were(0.69±0.15)and(0.79±0.18)g·cm-2;the BMD values of total hip were(0.70±0.11)and(0.77±0.15)g·cm-2;the BMD values of femoral neck were(0.79±0.19)and(0.87±0.15)g·cm-2,respectively;the OCN levels were(7.42±1.53)and(5.37±1.16)μg·L-1;the PINP levels were(85.31±5.66)and(76.30±5.49)ng·mL-1;the TRAP-5b levels were(3.27±0.46)and(5.16±0.72)U·L-1;the CTX-Ⅰ levels were(3.37±0.54)and(5.08±0.70)ng·mL-1;the VAS scores were(1.48±0.13)and(2.07±0.24)points;the ECOS-16 scores were(24.84±4.62)and(32.71±6.07)points,and there were statistical differences in the above indicators between treatment group and control group(all P＜0.05).The main adverse drug reactions in treatment group were rash,dizziness and limb pain,and the main adverse drug reactions in control group were rash,dizziness,nausea,and limb pain,and the total incidence rates of adverse reactions in treatment group and control group were 12.20％(5 cases/41 cases)and 19.51％(8 cases/41 cases)(P＞0.05).Conclusion Alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet has a significant short-term efficacy on PMOP patients,and it can help to enhance the bone mineral density,reduce the symptoms of bone pain,and relieve the osteoporosis.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.