OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.
Male ; Female ; Humans ; Middle Aged ; Carcinoma, Adenoid Cystic/surgery* ; Retrospective Studies ; Skull Base/pathology* ; Disease-Free Survival ; Prognosis

Objective: To summarize the clinical experience and treatment results of endoscopic transoral resection of metastatic retropharyngeal lymph nodes (MRPLN) in nasopharyngeal carcinoma (NPC) via posteroinferior eustachian tube approach. Methods: The clinical data of 37 patients with NPC who underwent endoscopic transoral surgery via posteroinferior eustachian tube approach for MRPLN in Xuanwu Hospital, Capital Medical University from 2010 to 2020 were analyzed retrospectively. There are 28 males and 9 females, aged from 31 to 72 years. The clinicopathological features such as gender, age, primary tumor stage, stage, side and size of MRPLN were recorded and analyzed. The surgical procedures of endoscopic transoral resection of MRPLN via posteroinferior eustachian tube approach were described. The MRPLN resection, perioperative complications and follow-up results were also summarized. Results: The primary tumors of 37 cases were determined as rT1 stage in 2 cases, rT2 stage in 30 cases and primary T2 stage in 5 cases in this study. There were 33 cases of unilateral MRPLN(89.2%), 4 cases of bilateral ones (10.8%), 36 cases in N1 stage, and 1 case in N3 stage. Single lymph node was detected in 23 cases(62.2%), and 2-5 lymph nodes in 14 cases(37.8%). Endoscopic transoral surgery via posteroinferior eustachian tube approach was completed in all cases. Total MRPLN resection was obtained in 35 cases (94.6%) with one-stage operation, and subtotal resection was achieved in 2 cases whose MRPLN involved the wall of internal carotid artery. No serious complications occurred in the perioperative period. During the follow-up period (median follow-up period 53.1 months), no recurrence of MRPLN was observed in patients who received total resection. And 8 patients (21.6%) died from different causes. Conclusion: Endoscopic transoral surgery via posteroinferior eustachian tube approach for MRPLN is a practicable and effective surgical option, but the long-term effect still needs longer follow-up and summary of bulk cases.
Humans ; Male ; Female ; Nasopharyngeal Carcinoma ; Eustachian Tube ; Retrospective Studies ; Lymph Nodes ; Nasopharyngeal Neoplasms

Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (n=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor β1 (AR-β1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-β1. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68⁺ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.
Animals ; Cross-Sectional Studies ; Ganglionectomy ; Heart Failure ; Male ; Mice ; Mice, Inbred C57BL ; Stroke Volume ; Ventricular Function, Left ; Ventricular Remodeling

We aimed to obtain the recombinant aminopeptidase encoded by Listeria monocytogenes (L. monocytogenes) gene lmo1711, and characterized the enzyme. First, the amino acid sequences of Lmo1711 from L. monocytogenes EGD-e and its homologues in other microbial species were aligned and the putative active sites were analyzed. The putative model of Lmo1711 was constructed through the SWISS-MODEL Workspace. Then, the plasmid pET30a-Lmo1711 was constructed and transformed into E. coli for expression of the recombinant Lmo1711. The his-tagged soluble protein was purified using the nickel-chelated affinity column chromatography. With the amino acid-p-nitroaniline as the substrate, Lmo1711 hydrolyzed the substrate to free p-nitroaniline monomers, whose absorbance measured at 405 nm reflected the aminopeptidase activity. The specificity of Lmo1711 to substrates was then examined by changing various substrates, and the effect of metal ions on the catalytic efficiency of this enzyme was further determined. Based on the bioinformatics data, Lmo1711 is a member of the M29 family aminopeptidases, containing a highly conserved catalytic motif (Glu-Glu-His-Tyr-His-Asp) with typical structure arrangements of the peptidase family. The recombinant Lmo1711 with a size of about 49.3 kDa exhibited aminopeptidase activity and had a selectivity to the substrates, with the highest degree of affinity for leucine-p-nitroaniline. Interestingly, the enzymatic activity of Lmo1711 can be activated by Cd²⁺, Zn²⁺, and is strongly stimulated by Co²⁺. We here, for the first time demonstrate that L. monocytogenes lmo1711 encodes a cobalt-activated aminopeptidase of M29 family.

Objective To research the monoclonal antibody KMP1 inhibited bladder cancer EJ cell lines growth and metastasis in vivo by bioluminescence imaging. Methods Immunohistochemistry was used to determine the KMP1 binding to EJ and EJ-GFP cell lines. The xenograft tumor cell growth and distribution were measured by vernier calipers and dynamic in vivo fluorescence imaging. Immunohistochemistry and H&E counterstaining researched the feature of the xenograft tumor. Results Cell growth curves of EJ and EJ-GFP cells were similar. EJ-GFP had a green fluorescence. In EJ-GFP nude mouse tumor model, the addition of KMP1 significantly inhibited tumor growth and extended the average life span of nude mice. Both EJ and EJ-GFP cells can bind to KMP1,and the weight of transplanted tumors in the KMP1 treatment group was significantly lower than that of the mIgG control group (P＜0.001).Conclusion KMP1 has a promising antitumor effect in vivo. It might be valuable for development as a promising targeted agent for bladder cancer.

Objective To investigate the relationship and the influence between pre-diabetes mellitus (PDM) and hyperuricemia (HUA).Methods 157 PDM patients,aged 20 to 75 years old were selected from the Second Clinical Medical College of Harbin Medical University,from 2009 February to 2010 February and were divided into HUA group (76 cases) and NUA group (81 cases).All the patients had not been on thiazide drugs.T-test and Pearson correlation analysis were used to calculate the differences and correlation between uric acid and biochemical indicators.Results In the HUA group,BMI was (27.74 ± 2.88) kg/m2,waist to height ratio (WSR) was (0.55 ± 0.41),TC was (6.61 ± 0.73) mmol/L,TG was (3.94 ± 1.97) mmol/L,LDL-C was (3.60 ± 0.45) mmol/L and homeostasis model assessment-insulin resistance index (HOMA-IR) was (3.09± 1.20).There were significant differences noticed in BMI,TG,TC,LDL-C,HOMA-IR at higher level in the HUA group than those in the NUA group.Pre-diabetes uric acid levels were positively correlated with TG,TC,LDL-C while HOMA-1R (TG:r=0.29,TC:r=0.33,LDL-C:r=0.49,HOMA-IR:r=0.51,P＜0.05)was negatively correlated (r=－0.30,P＜0.05) with the HbAlc.Conclusion The levels of PDM uric acid might both be related with TC,TG,LDL-C and HOMA-IR.The High level of uric acid status in vivo appeared closely related to HOMA-IR,which could further promote the progress of pre-diabetic patients to diabetes and causing dyslipidemia.Our findings suggested that the levels of pre-diabetes uric acid levels should be under concern.

Objective To observe the influence of silencing hypoxia-inducible factor-1α(HIF-1α)gene on the proliferation, invasion and metastasis of glioblastoma U87 cells. Methods The samples were divided into 3 groups: blank group: samples without giving any treatments, control group: cells with empty shRNA vector, and experimental group: cells with HIF-1α-shRNA transfection complex. HIF-1α gene was silenced by shRNA constructed in early time; and HIF-1α-shRNA lentivirus vector was constructed in the experimental group, and then transfected into glioblastoma U87 cells with the mediation of liposome. The interference efficiency was detected by using RT-PCR and Western blotting, and cell proliferation was measured by MTT assay; cell migration in vitro was observed by migration test, and invasion and metastasis abilities were detected by Transwell booth model. Results As compared with those in cells of the control and blank groups, the mRNA and protein expressions of HIF-1α in cells of the experimental group were significantly decreased; MTT assay showed that the cell proliferation in the experimental group was significantly lower than that in the other 2 groups (P<0.05). The number of penetrating cells of the blank group, control group and experimental group in Transwell chamber invasion assay were (125.2±10.8), (118.3±8.3), (60.9±5.4), respectively, and significant differences were noted between each 2 groups (P<0.05). Conclusion The mRNA and protein levels of HIF-1α in U87 cells are efficiently depressed by HIF-1α-shRNA, and so are the proliferation, invasion and metastasis abilities of U87 cells.