Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective:To detect the serum levels of 25(OH)D,miR-125b-5p,hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)in patients with multiple myeloma(MM),and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.Methods:Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included.Meanwhile,25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls.The serum level of 25(OH)D was monitored by mass spectrometry,the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR,and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay.The levels of 25(OH)D,miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.According to the level of 25(OH)D,the MM patients were divided into vitamin D deficiency group(＜20 ng/ml)and vitamin D non-deficiency group(≥ 20 ng/ml),and the levels of miR-125b-5p,HIF-1α,and VEGFA were compared between the two groups.The correlations between 25(OH)D,miR-125b-5p,HIF-1α and VEGFA were analyzed.The receiver operating characteristic(ROC)curve analysis was used to determine the diagnostic value of25(OH)D combined with miR-125b-5p for newly diagnosed MM.Results:The level of 25(OH)D in MM patients was significantly lower than that in control group(P＜0.01).There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients(P＞0.05).Compared with the control group,the level of miR-125b-5p was significantly reduced in MM patients(P＜0.01),while the levels of HIF-1α and VEGFA were significantly increased(both P＜0.001).In MM patients,the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group(P＜0.01),while the levels of HIF-1 α and VEGFA were significantly increased(both P＜0.05).In MM patients,25(OH)D was positively correlated with miR-125b-5p,while negatively correlated with HIF-1α and VEGFA(both P＜0.05).Moreover,miR-125b-5p was negatively correlated with HIF-1α and VEGFA(both P＜0.05).The area under the curve(AUC)for diagnosing MM with 25(OH)D,miR-125b-5p,and their combination were 0.699,0.751,and 0.791,respectively.Conclusion:The incidence of vitamin D deficiency is high in MM patients.Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P＜0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P＜0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P＜0.05),while no significant difference was found between the CS+MT and CS+HT groups(P＞0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P＜0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P＜0.05),with the CS+MT group having the lowest body weight(P＜0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P＜0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P＜0.05),with the CS+MT and CS+HT groups showing the lowest levels(P＜0.05).No significant difference was found between the CS+MT and CS+HT groups(P＞0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P＜0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P＜0.05),with the CS+MT group showing the lowest AUC for OGTT(P＜0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P＜0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P＜0.05),with no significant differences in TC and LDL-C levels between these two groups(P＞0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.

An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100％in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3％)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3％,100.0％,100.0％,and 98.9％;these values were significantly higher than those of VIDAS CDAB(60.0％,98.9％,91.3％,and 92.7％)(Kappa=0.714,OR=157.50,95％CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

The purpose of this study was to establish a luciferase immunosorbent assay(LISA)using the Crimean-Congo hemorrhagic fever virus(CCHFV)glycoprotein C(Gc),a specific antigen,for the detection of CCHFV IgG antibodies.Three antigenic fragments based on CCHFV glycoprotein C were designed,and three recombinant plasmids were constructed by liga-tion with the NanoLuc luciferase(NLuc)expression vector pNLF1-N through molecular cloning.The accuracy of the sequences in the recombinant plasmids was confirmed through sequencing.The recombinant plasmids were transfected into eukaryotic cells to obtain fusion proteins containing specific antigens and luciferase,and the expression of the fusion proteins was verified by western blotting,thereby facilitating the establishment of the CCHFV-LISA detection technique.The assay's sensitivity,specificity,and stability were evaluated and compared with those of a commercial CCHFV IgG antibody test kit.Three recom-binant antigen fragments of CCHFV Gc—NLuc-Gc-Full,NLuc-Gc-C1,and NLuc-Gc-C2—were expressed,with molecular weights of 80.1 kDa,62.8 kDa,and 53.9 kDa,respectively.The optimal fragment for CCHFV detection was NLuc-Gc-C2.The sensitivity of the CCHFV-LISA was 90.9％,and the specificity was 100％;the findings were highly concordant with those for the commercial CCHFV enzyme-linked immunosorbent assay kit.Repeatability tests indicated no statistically significant differ-ences in inter-and intra-assay variability within the same batch.The LISA was highly specific,sensitive,and user-friendly in detecting IgG antibodies against the CCHFV.Therefore,this method may facilitate serological diagnosis and epidemiological studies in endemic regions,and provide essential technical support for disease surveillance and early warning.