Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

This study was aimed at understanding the prevalence and drug resistance status of Salmonella of waterfowl ori-gin in the Guangdong region in the past decade,to guide prevention and control efforts.The drug-sensitive paper slide method was used to conduct drug susceptibility testing on 314 waterfowl-originating Salmonella strains isolated from 238 waterfowl farms in the Guangdong region from 2013 to 2023.The isolated Salmonella strains were most resistant to penicillin,amoxicil-lin,cefradine,and cefazolin in the β-lactam group;sulphadoxine dimethylpyrimidine in the sulphonamide group;and tetracy-cline in the tetracycline group.The resistance rates ranged from 73.57％to 89.49％.The highest sensitivity was observed to amikacin,gentamicin,and kanamycin in the aminoglycoside group,and norfloxacin in the quinolone group,with susceptibility rates all exceeding 50％.The 280 strains of Salmonella showed multi-drug resistance to six classes of antimicrobial drugs and high resistance(as much as 60.83％)to five drug classes.Correlation analysis revealed the highest correlations for florfenicol with gentamicin,and for amoxicillin with penicillin(r=0.650 for both),followed by gentamicin with kanamycin(r=0.620).Salmonella resistance in waterfowl in Guangdong Province was generally severe and showed a complex pattern of drug resist-ance.Detection of waterfowl pathogens should be strengthened to prevent the spread of drug-resistant bacteria and support ra-tional use of antibiotics.This work provides a reference for Salmonella prevention and control in waterfowl farms.

Objective To investigate the effects of DNA Cross-Link Repair 1A(DCLRE1A)on mitochondrial func-tion in lens epithelial cells(LECs).Methods Thirty eyes from 30 patients with age-related cataracts(ARC)were select-ed and divided into three groups:cortical type(ARCC group),nuclear type(ARNC group),and posterior subcapsular type(ARPC group),with 10 cases in each group.Additionally,10 eyes from 10 age-matched patients diagnosed with epiretinal membrane and having clear lenses were selected as the control group.Western blot was used to detect the ex-pression levels of DCLRE1A protein in the anterior capsule tissues of patients in each group and in the lens epithelial cell line(SRA01/04)treated with hydrogen peroxide(H2O2)in vitro and overexpressed DCLRE1A model(OE-DCLRE1A group).The effects of overexpressed DCLRE1A on the expression levels of mitochondrial transcription factor(TFAM)and peroxisome proliferator-activated receptor-γ coactivator-1α(PGC1α)proteins were also detected.Normal cultured SRA01/04 cells were randomly divided into Control group(untreated),H2 O2 group,H2 O2+HA group(transfected with control plasmid HA),and H2O2+OE-DCLRE1A group(transfected with DCLRE1A plasmid).RT-PCR was used to measure mtD-NA expression in each group cells.Changes in mitochondrial membrane potential(MMP)and mitochondrial reactive oxy-gen species(ROS)in each group were detected by immunofluorescence staining.Results Western blot analysis showed that compared with the control group cells,the relative expression levels of DCLRE1A protein in the anterior capsule tis-sues of patients in the ARCC,ARNC,and ARPC groups were all decreased,with statistically significant differences(all P＜0.001).In the in vitro H2O2-induced oxidative damage model,compared with the Control group,the relative expression level of DCLRE1A protein in the H2O2 group was significantly decreased(P＜0.001).The overexpression efficiency results of DCLRE1A showed that,compared with the Control group,the relative expression level of DCLRE1A protein in the OE-DCLRE1A group cells was significantly increased,with statistical significance(P＜0.001).RT-PCR results showed that compared with the H2O2+HA group,the expression level of mtDNA in the H2O2+OE-DCLRE1A group was significantly in-creased(P＜0.001).Western blot analysis showed that compared with the H2O2+HA group,the relative expression levels of TFAM and PGC1α proteins in the H2O2+OE-DCLRE1A group were significantly increased(P＜0.001).Immunofluores-cence staining results showed that compared with the H2O2+HA group,the MMP level in the H2O2+OE-DCLRE1A group was significantly restored,and the accumulation of mitochondrial ROS was reduced(P＜0.001).Conclusion Under H2O2-induced oxidative stress conditions,DCLRE1A promotes the repair of damaged mtDNA in LECs by regulating mito-chondrial biogenesis,thereby reducing LEC apoptosis and participating in the occurrence and development of ARC.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

OBJECTIVE: To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia. METHODS: Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected. RESULTS: Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027). CONCLUSION Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Acupuncture Therapy ; Depression/complications* ; Aged ; Young Adult ; Acupuncture Points ; Comorbidity

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*