1.Dual Targeting of TBK1 and JAK-STAT1 Pathways by (-)-epigallocatechin-3-gallate Suppresses Type I Interferon-driven Inflammation
Liang LI ; Qi-Huan SHENG ; Huan LIU ; Wen-Hao YANG ; Jia-Lin SHI ; Ying-Jie SUN ; Rui JING ; Wei-Hua MAI ; Zhi-Min LI ; Xiao-Li XIE
Progress in Biochemistry and Biophysics 2026;53(7):1969-1983
ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.
2.Brown Tumor: Rare Today, but Never to Be Forgotten
Min Jing Choo ; Liang Wei Wong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):77-
Introduction:
Brown tumors are rare skeletal manifestations of primary
hyperparathyroidism (PHPT), now seen in less than 5%
of cases due to widely accessible biochemical screening.
Despite being benign, they can mimic malignant bone
lesions, making diagnosis challenging.
Case:
A 45-year-old female presented with lethargy and
hypercalcemia (corrected calcium 3.5 mmol/L) and was
discharged after intravenous zoledronate. She returned
1 week later with an enlarging gingival mass present
for 2 months but not previously disclosed, with a strong
family history of malignancy. Examination revealed a 6
× 3 cm pedunculated lesion over the right alveolar ridge.
Biochemistry showed persistent hypercalcemia (2.7–2.9
mmol/L), hypophosphatemia, and elevated alkaline
phosphatase. Contrast-enhanced computed tomography of
the neck demonstrated lytic mandibular and skull changes,
raising suspicion for malignancy. Tumor markers and
multiple myeloma screening were negative. Parathyroid
hormone (PTH) later returned markedly elevated at 222.1
pg/mL (upper limit of normal 56.9 pg/mL), consistent
with PHPT, alongside concomitant vitamin D deficiency.
Excision biopsy of the mandibular lesion confirmed a
brown tumor on histopathology. Following preoperative
localization, she underwent left parathyroidectomy and
recovered without hungry bone syndrome. Histology
confirmed a parathyroid adenoma, and she has remained
normocalcemic since.
Brown tumors arise from prolonged osteoclastic activity
and represent advanced PHPT. Craniofacial involvement
is rare, with the mandible affected in 4–5% of cases,
and lesions may clinically and radiologically mimic
primary bone tumors or metastases, creating diagnostic
uncertainty. Hypercalcemia should be systematically
investigated to determine the underlying cause, with early
measurement of PTH to distinguish PTH-dependent from
PTH-independent etiologies. Untreated brown tumors
may result in bone pain, deformity, pathological fractures,
and functional impairment, highlighting the importance
of early detection and management.
Conclusion
Brown tumors, although rare, remain an important
differential diagnosis for lytic bone lesions in the context
of hypercalcemia. Early measurement of PTH and careful
clinical examination are essential to avoid misdiagnosis
and prevent disease-related morbidity.
Neoplasms
3.When Hyperprolactinemia Fails to Suppress: The Silent Gonadotroph in a Pituitary Macroadenoma
Min Jing Choo ; Liang Wei Wong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):85-
Introduction:
Pituitary macroadenomas may present with mass effects,
hypopituitarism, or hormone hypersecretion. Hyperprolactinemia, resulting from a prolactin-secreting tumor
or stalk compression, typically suppresses gonadotropins.
Thus, elevated follicle-stimulating hormone (FSH) and
luteinizing hormone (LH) with low testosterone in this
context are unusual. We report a macroprolactinoma with
a clinically non-functioning gonadotroph adenoma.
Case:
A 69-year-old male presented with acute giddiness and
headache while in Vietnam. He reported reduced libido
but no visual symptoms or galactorrhea. Examination
showed no neurological deficits, normal visual fields, and
secondary sexual characteristics; bilateral testes volume of
25 mL. Magnetic resonance imaging (MRI) brain revealed
a 1.6 × 2.2 × 2.1 cm pituitary macroadenoma compressing
the optic chiasm and pituitary stalk.
Initial pituitary evaluation demonstrated hyperprolactinemia (prolactin >200 µg/L; normal 2.4–13.1), central hypothyroidism (T4 6.8 pmol/L [7.8–14.4], thyroid-stimulating
hormone 2.3 mIU/L [0.38–5.3]), elevated FSH (21.5 IU/L
[1.2–19.2]) and LH (191 IU/L [1.24–8.62]), low testosterone
(8.88 nmol/L), normal insulin-like growth factor 1 (IGF-1)
(68 µg/L [46.5–191.9]), and cortisol 237 nmol/L. Cabergoline
was initiated at 0.25 mg twice weekly and titrated to 1
mg twice weekly over 4 months, alongside levothyroxine
25 µg daily.
Repeated MRI brain 2 months after cabergoline initiation
showed a persistent macroadenoma (1.7 × 2.2 × 2.2 cm) with
bilateral cavernous sinus extension. Prolactin decreased to
<170 µg/L, central hypothyroidism persisted; levothyroxine
was optimized, and hydrocortisone was initiated.
At the 5-month follow-up, prolactin further improved to
57 µg/L. Central hypothyroidism and borderline adrenal
function persisted, requiring continued replacement
therapy. Testosterone remained low-normal (10.2 nmol/L)
despite elevated FSH (15.4 IU/L) and LH (92 IU/L). Followup MRI and hormonal reassessment were planned in
May 2026.
Conclusion
Profoundly elevated prolactin level >200 µg/L and response
to cabergoline reflect true prolactinoma rather than stalk
effect. Persistently low testosterone with discordant high
FSH/LH suggests a non-functioning gonadotroph component producing biologically inactive gonadotropins. Definitive diagnosis requires histopathological confirmation,
while serial biochemical and radiological follow-up guides
management and clarifies tumor subtype.
Gonadotrophs
;
Hyperprolactinemia
4.Evaluation on the Efficacy and Advantages and Mechanisms of TCM in Preventing and Treating"Inflammation-cancer Transformation"of Colorectal Adenoma-colorectal Cancer
Xiaojuan TANG ; Yuan REN ; Min HE ; Liang ZHAO ; Yuan LYU ; Yongmin LI ; Jing HUANG ; Yongheng HE
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):20-24
Colorectal adenoma is a definite precancerous lesion,and the"inflammation-cancer transformation"is a key pathological link in the process of colorectal adenoma-cancer evolution.Under the guidance of the theory of"preventive treatment of diseases"in TCM,prevention before disease onset and preventing the development of the occurred disease has become the consensus and the important subject of clinical research to block the"inflammation-cancer transformation"and prevent the precancerous lesions of colorectal cancer.This article discussed the effectiveness of TCM in preventing and treating the"inflammation-cancer transformation"from different aspects.Its advantages are reflected in improving the symptoms of TCM and improving the quality of life,etc.Its mechanism may be related to inhibiting the activation of cancer-promoting signals,regulating inflammation,maintaining intestinal microbial homeostasis,and protecting the intestinal barrier.By explaining the pathogenesis of adenoma-cancer transformation in TCM,this article discussed the efficacy and advantages of TCM to block"inflammation-cancer transformation",analyzed its intervention targets and pathways,providing references for the intervention of TCM in the management of precancerous lesions of colorectal cancer and the synergistic prevention and treatment of traditional Chinese and Western medicine.
5.Present situation of sensors applied to monitoring of spinal morphology and motion
Shi-yu ZHOU ; Ya-qin LI ; Yang-xi HUANG ; Xiao CHEN ; Jing WANG ; Zhi-min LIANG ; Yu-chen GUO ; Xue YANG ; Ling-li LI
Chinese Medical Equipment Journal 2025;46(6):105-110
The application of sensors to the monitoring of spinal morphology and motion was reviewed in terms of the research object and monitoring index.The present situation of the application of sensors was introduced,such as inertial sensor,stretchable strain sensor and electromagnetic sensor.The deficiencies of sensors applied to the monitoring of spinal morphology and motion were analyzed,and the future directions of the application were pointed out.[Chinese Medical Equipment Journal,2025,46(6):105-110]
6.Present situation of sensors applied to monitoring of spinal morphology and motion
Shi-yu ZHOU ; Ya-qin LI ; Yang-xi HUANG ; Xiao CHEN ; Jing WANG ; Zhi-min LIANG ; Yu-chen GUO ; Xue YANG ; Ling-li LI
Chinese Medical Equipment Journal 2025;46(6):105-110
The application of sensors to the monitoring of spinal morphology and motion was reviewed in terms of the research object and monitoring index.The present situation of the application of sensors was introduced,such as inertial sensor,stretchable strain sensor and electromagnetic sensor.The deficiencies of sensors applied to the monitoring of spinal morphology and motion were analyzed,and the future directions of the application were pointed out.[Chinese Medical Equipment Journal,2025,46(6):105-110]
7.A Cross-sectional Study of Blood Glucose and Biochemical Indicators in Pediatric Patients with Hepatic Glycogen Storage Disease
Ni MA ; Haotian WU ; Ying WANG ; Jing YANG ; Danxia LIANG ; Min YANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):132-137
[Objective]Patients with hepatic glycogen storage disease(GSD)have recurrent episodes of hypoglycemia.This study aimed to investigate and analyze blood glucose and biochemical indicators in pediatric patients with hepatic GSD,thus provide data support for hypoglycemia prevention and its clinical management.[Methods]A cross-sectional field study was conducted among patients with hepatic GSD treated in the Department of Pediatrics of Guangdong Provincial People's Hospital on July 14,2024.We collected the peripheral blood samples of the patients and their healthy family controls on site,then analyzed and compared their blood glucose and biochemical indicators.[Results]Of the 44 patients with hepatic GSD,there were 34 males and 10 females,including GSD Ib(n=14),GSD Ia(n=15),GSD Ⅲ(n=2),GSD Ⅵ(n=7)and GSD Ⅸ(n=6).The average age was 7.60(5.08-11.98)years.All patients were on uncooked cornstarch(UCCS)therapy.Of the patients,77.3%(34/44)had hepatomegaly,61.4%(27/44)had recurrent hypoglycemia,61.4%(27/44)had blood glucose≤3.9 mmol/L,18.2%(8/44)had blood glucose≤2.8 mmol/L,and none of the 8 cases was GSD Ib.The lowest blood glucose level was 1.19 mmol/L and no episodes of hypoglycemia occurred.Of the family control subjects,65.9%(29/44)had blood glucose≤3.9 mmol/L.There was no significant difference in hypoglycemia prevalence between hepatic GSD group and control group(P=0.658).The hepatic GSD patients had hyperlactacemia,hyperuricemia and hypercholesterolemia prevalence rates of 65.9%,45.5%and 9.1%,respectively,as compared with 18.2%,43.2%and 15.9%,respectively,for the family control subjects.No significant difference was found in the prevalence rates of hyperuricemia and hypercholesterolemia between the two groups(P=0.830 and P=0.334,respectively).[Conclusions]Asymptomatic hypoglycemia is common in patients with hepatic GSD,especially in non-GSD-Ib patients.It is necessary to optimize the diet management of UCCS,conduct dynamic blood glucose monitoring and follow a light diet,so as to decrease hyperuricemia and hypercholesterolemia,avoid and reduce the serious adverse reactions and complications caused by severe hypoglycemia.
8.Molecular epidemiological characteristics and hypervirulence evolution of ST11 carbapenem-resistant Klebsiella pneumoniae in medical institutions in Shanghai
Jing BI ; Wenjie CHEN ; Liang TIAN ; Qian LIU ; Huanyu WU ; Min CHEN ; Taiyao CHEN ; Tingting SHI ; Wei MA ; Hongzhi ZHANG
Chinese Journal of Infection Control 2025;24(8):1075-1082
Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03%of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24%(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.
9.Contamination risk and drug resistance analysis of Klebsiella pneumoniae in a medical institution in Minghang District, Shanghai, 2021‒2023
Sijia ZHANG ; Xing ZHANG ; Liang TIAN ; Yibin ZHOU ; Xiaosa WEN ; Jing WANG ; Zhiyin XU ; Min WU
Shanghai Journal of Preventive Medicine 2025;37(4):289-295
ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ2=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ2=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ2=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ2=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ2=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ2=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.
10.Environmental Temperature and the Risk of Hand, Foot, and Mouth Disease Transmission in the Yangtze River Region of China.
Yan Qing YANG ; Min CHEN ; Jin LI ; Kai Qi LIU ; Xue Yan GUO ; Xin XU ; Qian LIANG ; Xing Lu WU ; Su Wen LEI ; Jing LI
Biomedical and Environmental Sciences 2025;38(3):290-302
OBJECTIVE:
To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors.
METHODS:
From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact.
RESULTS:
Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution.
CONCLUSION
The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female
;
Humans
;
Male
;
China/epidemiology*
;
Cities/epidemiology*
;
Hand, Foot and Mouth Disease/transmission*
;
Incidence
;
Risk Factors
;
Temperature


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