Objective To understand the equity and influencing factors of maternal health service utilization in Changning District, Shanghai. Methods A convenience sampling method was used to conduct a questionnaire survey among mothers of children aged 1 to 1.5 years old who received health services from the child health care clinics and EPI clinics of 10 community health service centers in Changning District, Shanghai from March to April 2022. Count data was expressed by frequency and percentage. Chi-square analysis, binomial logistic regression analysis, and multivariate logistic regression analysis were used to analyze fairness-related factors. Rate difference, rate ratio and concentration index were used to represent fairness. Results A total of 696 subjects were investigated, with an average age of (33.35±4.76) years. There were statistically significant differences in service utilization among women with different household registrations only in early pregnancy registration (χ²=11.026, P=0.001) and postpartum visits (χ²=4.989, P=0.026). Women with a career showed differently in folic acid supplement (χ²=6.247, P=0.012), early pregnancy registration (χ²=12.989, P=0.002), physical examination in 42 days postpartum (χ²=4.446, P=0.035) and postpartum contraception (χ²=4.061, P=0.044), and the differences were statistically significant. Women with different monthly family income had a statistically significant difference in pre-pregnancy examination (χ²=8.977, P=0.030) and postpartum visit (χ²=16.114, P=0.001). There was a statistically significant difference between women with maternity insurance or not in the early pregnancy registration (χ²=10.576, P=0.001) and physical examination in 42 days postpartum (χ²=8.166, P=0.004). The results of the multivariate analysis showed that occupation (OR=2.616, 95% CI: 1.142-5.990) and maternity insurance (OR=4.490, 95% CI: 1.992~10.120) affected the utilization of service in early pregnancy registration. The monthly household income (OR=0.278, 95% CI: 0.124-0.625) affected the utilization of services in postpartum visit. At the same time, the monthly household income (10,000-19,999: OR=0.286, 95% CI: 0.090-0.907; ≥30,000: OR=0.180, 95% CI: 0.041-0.801) also affected the utilization of service in physical examination in 42 days postpartum. Conclusion The equity of maternal health care service utilization overall is good in central area in Shanghai, but there is still room for improvement. It is necessary to strengthen community mobilization, propagandize maternal health services, and expand the coverage of maternity insurance to improve the equity of maternal health service utilization and provide equal access to maternity health services.

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective To observe the characteristics of gut microbiota in patients with type 2 diabetes mellitus(T2DM)with different traditional Chinese medicine(TCM)syndrome types,and to further explore the key microbial communities and functional differences affecting syndrome differentiation.Methods A total of 45 patients who visited the Department of Geriatrics,Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine in 2023 were enrolled.These included 15 T2DM patients with qi-yin deficiency and blood stasis syndrome(Group A),15 T2DM patients with qi-yin deficiency syndrome(Group B),and 15 non-diabetic patients from the same period(Group C).Fecal samples were collected,and 16S rRNA sequencing and analysis were performed.Results 1)A total of 1 564 operational taxonomic units(OTUs)were obtained from the three groups of patients,with 224,127,and 351 unique OTUs identified in Groups A,B and C,respectively.2)Both α-and β-diversity analyses indicated differences among the gut microbiota of the three groups.For instance,in the α-diversity analysis,the Sobs index showed significant inter-group differences(P＜0.01).Group A(264.00±88.84)was significantly higher than Group B(145.90±87.0)(P＜0.01),while Group B was significantly lower than Group C(229.7±112.4)(P＜0.05).In the β-diversity analysis,the principal coordinate analysis(PCoA)indicated a clear separation among groups(R=0.1610,P＜0.01).The R values in the Anosim/Adonis analysis ranged from 0.144 to 0.196,and the R2 values ranged from 0.067 to 0.083,all indicating differences in inter-group comparisons(P＜0.01).3)At the phylum level,Firmicutes,Actinobacteriota,and Bacteroidota were predominant in all groups.Among them,Bacteroidota exhibited significant inter-group differences(P＜0.05),with its abundance in Group A being significantly higher than that in Group B(P＜0.01).4)Analysis of differences in microbiota composition,combined with linear discriminant analysis effect size(LEfSe)and Random Forest analysis,revealed that,at the genus level,the microbiota biomarkers between Group A and Group B were Parabacteroides,Bacteroides,g_unclassified_f_Lachnospiraceae,Roseburia,and Aspergillus,those between Group B and Group C were Erysipelotrichaceae_UCG-003 and Ruminococcus,and those between Group A and Group C were Parabacteroides,Anaerotruncus,and Oscillibacter.The results were validated by receiver operating characteristic(ROC)curve analysis,which suggested that the microbiota biomarkers between Group A and Group B(AUC=0.91;95％CI,0.80-1.00),Group B and Group C(AUC=0.84;95％CI,0.69-0.99),Group A and Group C(AUC=0.87;95％CI,0.75-0.99)had good diagnostic efficacy.5)The study identified 116 major pathways with inter-group differences through Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.For example,the enrichment degree of ABC transporter pathway in Group A(2.58±0.36)was significantly lower than those in Group B(2.90±0.48)and Group C(3.11±0.66)(P＜0.05).These pathways were associated with metabolism and environmental information processing.g.Conclusion The differences in the gut microbiota characteristics and functions among patients with specific TCM syndromes of T2DM may provide references for TCM syndrome differentiation and therapeutic mechanisms.

Objective To observe the clinical efficacy and safety of lupatadine tablets combined with azelastine hydrochloride nasal spray in the treatment of allergic rhinitis patients.Methods Patients with allergic rhinitis were randomly divided into control group and treatment group.Both groups received general treatment.On this basis,the control group was given azelastine hydrochloride nasal spray 0.14 mg per nostril each time,bid;on the basis of control group,the treatment group received lupatadine tablets 10 mg each time,orally,qd.Two groups were treated for 4 weeks.The clinical efficacy,rhinoconjunctivitis related quality of life questionnaire(RQLQ),serum indexes[interleukin-6(IL-6),IL-1 β,tumor necrosis factor-α(TNF-α),immunoglobulin E(IgE)]and safety were compared between the two groups.Results Treatment group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.Control group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.After treatment,the total effective rates of the treatment and control groups were 95.92％(47 cases/49 cases)and 81.63％(40 cases/49 cases)with significant difference(P＜0.05).After treatment,the RQLQ scores of treatment and control groups were(49.57±6.97)and(58.18±7.78)points,IL-6 levels were(5.12±1.25)and(7.34±1.46)ng·L-1,IL-1 β levels were(12.25±5.64)and(20.05±6.32)pg·mL-1,TNF-α levels were(3.25±0.62)and(4.45±0.49)pg·mL-1,the IgE levels were(114.28±19.63)and(136.84±30.14)μg·L-1,respectively,the differences were statistically significant difference(all P＜0.05).The adverse drug reactions of two groups were dry mouth,fatigue,dizziness and drowsiness.The total incidences of adverse drug reactions in the treatment and control groups were 16.33％and 10.20％without significant difference(P＞0.05).Conclusion Lupatadine tablets combined with azostine hydrochloride nasal spray have a definitive clinical efficacy in the treatment of allergic rhinitis patients,which can effectively reduce the inflammatory reaction,reduce the IgE levels,improve the quality of life,without increasing the incidence of adverse drug reactions.

ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol^-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.

Objective To explore the potential value of three-dimensional fast spin echo(3D-SPACE)combined with multilayer spiral CT(MSCT)in the diagnosis of knee cruciate ligament injury,to provide a new direction for the optimization of subsequent clinical diagnosis.Methods A total of 120 patients with knee cruciate ligament injury were treated from April 2020 to April 2021,aged from 21 to 68 with an average of(41.52±4.13)years old.For all patients,separate MSCT scanner scans,3D-SPACE sequence scans alone and 3D-SPACE sequence combined with MSCT scans were used.The injury and classifica-tion of the anterior and posterior cruciate ligament of the knee were compared,the length of the anterior-medial bundle and posterolateral bundle and its angle of the knee with the horizontal plane were observed,the diagnostic value of 3 diagnostic methods in knee cruciate ligament injury were determined.Results There was no significant difference between the 3D-SPACE sequence scan alone and the MSCT test alone on the total diagnostic rate and grading total diagnostic rate(P＞0.05).The total diagnostic rate and grading total diagnostic rate of 3D-SPACE scan combined with MSCT were significantly higher than those of 3D-SPACE scan or MSCT alone(P＜0.05).The 3D-SPACE sequence scan alone and the MSCT detection alone had no signifi-cant difference in the measurement values related to the anterior and posterior cruciate ligaments of the knee joint(P＞0.05).3D-SPACE sequence scanning combined with MSCT detection on the knee joint anterior and posterior cruciate ligament related mea-surements were significantly higher than the 3D-SPACE sequence scan or MSCT detection alone(P＜0.05).The area under the ROC curve estimated by 3D-SPACE sequence scanning combined with MSCT was 0.960,which was significantly higher than that of 3D-SPACE sequence scanning and MSCT alone evaluating the area under the ROC curve line of 0.756 and 0.795.The com-bined 3D-SPACE sequence scanning and 3D-SPACE sequence scanning MSCT analysis and prediction models were statistically different(Z=2.236,P＜0.05),and MSCT alone and 3D-SPACE sequence scanning combined with MSCT analysis and prediction models were statistically different(Z=2.653,P＜0.05).Conclusion The application of 3D-SPACE sequence combined with MSCT scanning for knee cruciate ligament injury can improve the diagnosis rate of patients with knee cruciate ligament injury.It can be used as a diagnostic tool for patients with knee cruciate ligament injury and is worthy of clinical application.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.