This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

With the aging of the population, Alzheimer’s disease（AD）has become a common disease in the elderly. Because of its complex pathogenesis and the limited clinical drugs which can only improve the symptoms, traditional Chinese medicine（TCM）shows great potential in the prevention and treatment of AD. Its multi-component and multi-target characteristics coincide with the network pharmacology concept of regulating multiple targets signal pathways. The common websites and tools of network pharmacology, as well as the application of network pharmacology in the research of AD were summarized, which provided reference for further research on the prevention and treatment of AD using traditional Chinese medicine.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective: To investigate the relationship between pubertal timing and depressive symptoms among high school students in Suzhou, so as to provide scientific evidence for promoting adolescents mental health. Methods: From October 2023 to January 2024, 3 369 students were selected from 20 high schools in Suzhou using stratified cluster random sampling method. Physical examinations and questionnaire surveys were conducted. The Preece & Baines growth Model 1 was used to calculate the age at take off of height velocity (ATO) and age at peak height velocity (APHV), categorizing students into three groups: early pubertal timing group (< P 15 ), ontime group ( P 15 - P 85 ), and delayed group (> P 85 ). Binary Logistic regression was used to analyze its association with depressive symptoms. Results: The ATO for male and female high school students in Suzhou was (9.35±1.23) and ( 8.12 ±1.52) years old, respectively. The mean APHV was (12.35±0.74) years old for boys and (10.91±0.82) years old for girls. The overall prevalence of depressive symptoms was 34.22%, with no statistically significant gender difference ( χ 2=0.42, P =0.52). Significant differences in depressive symptom prevalence were observed across grade levels, breakfast frequency, weekly days of moderate to vigorous physical activity, daily sleep duration, history of school bullying, and the presence of Internet addiction ( χ 2=5.03-69.21, all P < 0.05 ). After adjusting for age, body mass index, region, boarding status, breakfast frequency, weekly moderate to vigorous physical activity days, sleep duration, campus bullying, and presence of Internet addiction, Logistic regression analysis revealed that when ATO was used to evaluate pubertal timing, the risk of depressive symptoms in the delayed group of boys was 1.65 times that of the on time group (95% CI =1.24-2.19); when APHV was used to evaluate pubertal timing, the risks of depressive symptoms in the early pubertal timing group and delayed group of boys were 1.43 times (95% CI =1.07-1.91) and 1.41 times (95% CI =1.05-1.88) of that of the on time group, respectively (all P <0.05). No statistically significant associations were found among females (all P > 0.05 ). Conclusion The prevalence of depressive symptoms among high school students in Suzhou is relatively high, and both early and delayed puberty timing in boys are associated with depressive symptoms.

Objective: To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia. Methods: A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes. Results: The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05). Conclusions Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

Zirconium dioxide(ZrO2)is a suitable solid phase microextraction(SPME)fiber coating due to its high thermal and chemical stability and excellent adsorption.Similarly,polydopamine(PDA)can also be utilized as SPME fiber coating because of its strong oxidation resistance and stability,desired adsorption as well as environmental friendliness.In this work,a novel zirconium dioxide-doped polydopamine(ZrO2@PDA)SPME fiber coating was quickly fabricated on the stainless steel(SS)by cyclic voltammetry(CV)using the etched SS wire as working electrode,a Pt rod as counter electrode and a saturated calomel electrode as reference electrode.Coupled with high performance liquid chromatography-ultraviolet detection(HPLC-UV),the extraction performance of the fabricated SS@ZrO2@PDA fiber was evaluated using typical aromatic compounds of polycyclic aromatic hydrocarbons(PAHs),ultraviolet filters(UvFs),phthalate acid esters(PAEs)and chlorophenols(CPs).The SS@ZrO2@PDA fiber showed excellent extraction capability for PAHs and PAEs,however,poor extraction capability for UvFs and no extraction capability for CPs.Therefore,PAHs were selected as target analytes and the key experimental factors on extraction efficiency were optimized.Under the optimized conditions,good linearity was obtained for the developed SPME-HPLC-UV method with the SS@ZrO2@PDA fiber.The limits of detection(LODs,S/N=3)were 0.018-0.082 μg/L.The developed method was successfully applied to determination of trace PAHs in different actual water samples with recoveries of 86.7%-102.4%and RSDs less than 8.2%.In addition,the fabricated novel fiber was simple to prepare and exhibited high stability,good reproducibility and long service life.