Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology, primarily characterized by systemic inflammation and hyperactivation of both B and T lymphocytes. Key immunological features include increased consumption of complement components, sustained overproduction of type I interferons (IFN-I), and persistent production of a broad spectrum of autoantibodies, such as anti-dsDNA antibodies. However, the use of autoantibodies as biomarkers for the early detection of SLE is associated with a high false-positive rate, suggesting that antibody characteristics evolve during disease progression.N-glycosylation is a critical post-translational modification of antibodies that significantly influences their structure and receptor-binding properties, thereby modulating biological activities and functions. In particular, glycosylation patterns affect the antibody’s affinity for Fc gamma receptors (FcγRs), subsequently regulating various antibody-mediated immune responses. Numerous studies have investigated the impact of individual monosaccharides—such as sialic acid, fucose, and N-acetylglucosamine, which constitute N-glycans—on the immunological functions of antibodies. This review systematically summarizes the aberrant immunoglobulin G (IgG) N-glycosylation patterns observed in SLE patients, with a focus on correlations between disease progression or complications and quantitative alterations in individual glycan components. We first review how different types of N-glycosylation modifications affect the biological activity and functional properties of IgG, particularly regarding the effects of specific monosaccharides—such as sialic acid, fucose, and galactose—on FcγR binding affinity and the resulting downstream immune functions. We then summarize the differential expression of IgGN-glycans and glycosyltransferase genes between SLE patients and healthy controls, and outline the associations between glycosylation changes and SLE-related pathological responses. In response to the inconsistencies and limitations in current research, we propose potential explanations from the perspectives of study methodologies, participant characteristics, and variations in N-glycan structures, aiming to provide a constructive reference for future studies. Given the close relationship between antibody glycosylation and SLE, this review highlights the potential of IgG N-glycosylation patterns as promising biomarkers for early diagnosis and disease monitoring. In terms of therapy, we discuss how IgG glycosylation can enhance the efficacy of intravenous immunoglobulin (IVIg) treatment and introduce emerging therapeutic strategies that aim to modulate endogenous IgG N-glycans as a novel glycan-based approach for SLE management. In summary, N-glycans are essential structural components of antibodies that regulate immune responses by modulating antibody-receptor interactions. Aberrant glycosylation is closely associated with the pathogenesis of autoimmune diseases, including SLE. However, due to the structural diversity of N-glycans and the complexity of glycosylation processes, the precise roles of IgGN-glycosylation in SLE pathophysiology remain incompletely understood. Moreover, therapeutic strategies targeting IgG glycosylation are still in early development and have not yet reached clinical application. Continued progress in glycan analysis technologies and other biological tools, along with interdisciplinary collaboration, will be essential for advancing this field.

[摘 要] 目的：探索外周免疫功能状态与肺癌转移的关联，筛选可用于肺癌转移“正虚”评估的外周血免疫标志物。方法：回顾性分析2023年3月至2025年4月期间上海中医药大学附属市中医医院收治的肺癌患者治疗前的外周血免疫标志物，根据是否存在远处转移，将患者分为无转移组与转移组，比较两组间免疫细胞和细胞因子的表达差异。将单因素分析P < 0.05的外周血免疫指标纳入多因素二元Logistic回归模型，以识别肺癌转移的独立预测因素。结果：共纳入193例肺癌患者（无转移组101例，转移组92例），两组在性别、年龄、吸烟史、饮酒史、病理类型间的差异均无统计学意义（均P > 0.05）。单因素分析显示，无转移组与转移组间有多项免疫指标存在显著差异（均P < 0.05），包括：淋巴细胞计数，CD3+、CD4+、CD8+ T、CD19+ B细胞及CD3-CD16+56+ NK细胞绝对计数，Treg细胞、CD8+CD28+ Treg细胞、G-MDSC和CD3-CD16+CD56+dim NK细胞百分率，以及细胞因子IL-1β、IL-6和IL-10水平。将差异性指标行二元Logistic回归分析，提示外周血中Treg细胞和CD8+CD28+ Treg细胞百分率是肺癌发生远处转移的独立预测因素[OR = 1.193, 95% CI（1.047, 1.36）, P < 0.01; OR = 0.978, 95% CI（0.957, 0.999）, P < 0.05]。结论：外周血免疫功能紊乱是肺癌转移“正虚”的生物学基础，本研究以量化指标证实外周免疫功能状态与肺癌转移的相关性，为“正虚伏毒”和“肿瘤转移态”理论提供了实证。

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To evaluate the bioequivalence and safety of two voriconazole for injection in healthy Chinese subjects,and to explore the safety of the excipient sulfobutyl-β-cyclodextrin.Methods A single-center,single-dose,randomized,open-label,two-preparation,two-period,double-crossover trial design.A total of 18 healthy subjects were enrolled and administrated with a single intravenous infusion of voriconazole test drug and reference drug at 4 mg·kg-1 under fasting conditions,with a sequence determined by randomization.The concentrations of voriconazole in plasma and sulfobutyl-β-cyclodextrin in urine were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters of voriconazole in plasma,and SAS(version 9.4)software was used to calculate pharmacokinetic parameters of sulfobutyl-β-cyclodextrin in urine and bioequivalence analysis.Results Major pharmacokinetic parameters of voriconazole in plasma after a single intravenous infusion of voriconazole test drug and reference drug in 18 healthy subjects in a fasted state were as follows:Cmax were(2 177.00±399.10)and(2 265.00±378.70)ng·mL-1;AUC0-t were(14 612.07±8 182.95)and(15 144.69±7 814.02)ng·h·mL-1;AUC0-∞ were(16 217.48±10 862.78)and(16 863.18±10695.75)ng·h·mL-1;tmax were 2.00 and 1.98 h,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the two drugs were within the equivalence range of 80.00％to 125.00％.Conclusion The two voriconazole for injection preparations were bioequivalent and safe when administered by intravenous infusion under fasting conditions in healthy Chinese subjects.

BACKGROUND:There are few studies on the effect of degeneration of paraspinal muscle on osteoporotic vertebral compression refractures treated by percutaneous vertebroplasty in postmenopausal women.This paper intends to reveal the relationship between them. OBJECTIVE:To investigate the relationship between degeneration of paraspinal muscle and osteoporotic vertebral compression refractures in postmenopausal women treated by percutaneous vertebroplasty. METHODS:The medical records of 81 postmenopausal female patients who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2018 to March 2021 for osteoporotic vertebral compression fracture and received percutaneous vertebroplasty were retrospectively analyzed.The patients were divided into an osteoporotic vertebral compression refracture group(n=39)and a control group(n=42)according to whether they had osteoporotic vertebral compression refracture after percutaneous vertebroplasty.General data,vertebral bone mineral density,paravertebral cross-sectional area and mean CT value(Hu)of the two groups were analyzed. RESULTS AND CONCLUSION:(1)Univariate analysis showed that there was no significant difference in age and mean CT value of psoas major between the two groups(P>0.05).The body mass index,vertebral bone mineral density,paravertebral cross-sectional area and the mean CT value of the posterior vertebral muscle group in the control group were significantly higher than those in the osteoporotic vertebral compression refracture group(P<0.05).(2)Multivariate logistic regression analysis showed that low vertebral bone mineral density(OR=0.004,95%CI:0.000-0.555,P<0.05)and low mean CT value of posterior vertebral muscle group(OR=0.940,95%CI:0.894-0.988,P<0.05)were independent risk factors for postmenopausal osteoporotic vertebral compression refracture.(3)It is indicated that degeneration of paraspinal muscle will increase the risk of osteoporotic vertebral compression refractures in patients treated by percutaneous vertebroplasty,especially in postmenopausal women with a low mean CT value of low posterior vertebral muscle group.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

ObjectiveTo observe the clinical efficacy of modified Yigongsan combined with multi-enzyme tablets and bifidobacterium triple live powder on infantile anorexia with spleen-stomach Qi deficiency syndrome. MethodA total of 112 infantile patients anorexia with spleen-stomach Qi deficiency syndrome treated at Hebei Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were enrolled and divided into a control group and an observation group， with 56 cases in each group， according to a random number table. Children in the control group were treated with multi-enzyme tablets and Bifidobacterium triple live powder， while those in the observation group were treated with modified Yigongsan in addition to the treatment in the control group. During the study， one case dropped out in the control group and two cases dropped out in the observation group. The clinical efficacy of the two groups of children was compared， including changes in traditional Chinese medicine （TCM） syndrome scores （main symptoms， secondary symptoms， tongue， and pulse）， time to restore normal food intake， and increase in body weight. Changes in calcium， iron， zinc levels， hemoglobin， and albumin levels before and after treatment， as well as changes in gastrointestinal hormones such as gastrin and motilin， vasoactive intestinal peptide， somatostatin， neuropeptide Y， orexin， and leptin， were observed. The occurrence of adverse reactions in the two groups of children during the study was also recorded. ResultThe total effective rate of children in the control group after treatment was 85.19% （46/54）， while that in the observation group was 98.15% （53/54） （χ² =5.939， P<0.05）. Compared with the control group， the time for food intake to return to normal in the observation group was shorter， and the increase in body weight was greater （P<0.05）. Compared with the results before treatment， the TCM syndrome scores （main symptoms， secondary symptoms， tongue， and pulse） in both groups of children significantly decreased， while the levels of calcium， iron， zinc， hemoglobin， albumin， gastrin， motilin， neuropeptide Y， and orexin increased， and the levels of vasoactive intestinal peptide， somatostatin， and leptin decreased （P< 0.01）. Compared with the control group after treatment， the improvement in the above indicators in the observation group was more significant （P<0.01）. The incidence of adverse reactions in the two groups of children during the treatment period was similar， and the difference was not statistically significant. ConclusionModified Yigongsan combined with multi-enzyme tablets and Bifidobacterium triple live powder is highly effective in treating infantile anorexia （spleen-stomach Qi deficiency syndrome）. After treatment， symptoms of the children were improved，appetite and food intake increased， gastrointestinal function was improved， body weight increased， and adverse reactions were few， indicating that the treatment was safe and reliable.

Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.