1.Effect and Mechanisms of Ermiao Formula Analogs and Their Active Components in Treating Dampness-heat Type Gouty Arthritis: A Review
Xueping ZHAO ; Xinya ZHANG ; Le YANG ; Ye SUN ; Xin SUN ; Hui SUN ; Qimeng ZHANG ; Guangli YAN ; Xijun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):276-285
Gouty arthritis (GA) is caused by monosodium urate(MSU) deposition due to purine metabolism disorders. In traditional Chinese medicine (TCM), it falls under the category of "dampness-heat Bi syndrome", with core pathogenesis involving dampness-heat accumulation and dysfunction of the spleen and kidney. The dampness-heat syndrome is the most common and the primary syndrome type during acute attacks. In Western medicine, GA is associated with purine metabolism imbalance and inflammation triggered by MSU crystals, involving pathways such as NOD-like receptor protein 3 (NLRP3) inflammasome activation and Toll-like receptor 2/4 (TLR2/4) signaling. Clinically, colchicine and similar drugs are commonly used to treat GA, although long-term use carries potential side effects. Ermiao Formula analogs originate from ancient prescriptions, including Ermiao, Sanmiao, and Simiao compound formulas. All contain Atractylodis Rhizoma and Phellodendri Chinensis Cortex. Ermiaowan follow a 1∶1 formulation ratio. Sanmiaowan add Cyathulae Radix. Simiaowan further incorporate Coicis Semen. These formulas are rich in active ingredients, including alkaloids, terpenoids, flavonoids, and sterols, and treat GA through multi-component, multi-pathway, and multi-target mechanisms. Ermiaosan primarily exerts anti-inflammatory effects by inhibiting pathways such as TLR4/nuclear factor kappa-B (NF-κB) or regulating immune responses to reduce the release of inflammatory mediators, while also suppressing xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activity to decrease uric acid production. Sanmiaowan enhance uric acid-lowering and anti-inflammatory effects through the guiding herb Cyathulae Radix, while also protecting cartilage from damage. Simiaowan utilizes Coicis Semen to regulate intestinal flora, alleviate dampness-heat symptoms, and exert multi-pathway anti-inflammatory and uric acid-lowering effects. The active ingredients contribute differently to uric acid metabolism regulation, anti-inflammation, antioxidant activity, and bone repair, resulting in varying therapeutic effects due to differences in formula composition. In summary, formulas derived from Ermiaosan demonstrate significant efficacy in treating dampness-heat type GA. This review summarizes their research progress and mechanisms, providing a reference for clinical application, new drug development, and further studies.
2.Construction and validation of a prognostic risk assessment model for lung adenocarcinoma based on miR-34 family target genes
Lingyu GU ; Ang GELEMA ; Dan YANG ; Huifeng WANG ; Lixin WANG ; Hui DONG
Acta Universitatis Medicinalis Anhui 2026;61(1):118-126
ObjectiveTo establish a tumor prognostic risk assessment model related to target genes of the miR-34 family. MethodsTarget genes of the miR-34 family were screened, and the scores of miR-34 target genes were assessed in 16 tumor types. Univariate Cox regression analysis was used to identify the tumor type with the strongest correlation between miR-34 target gene scores and overall survival (OS). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functional roles and signaling pathways of miR-34 target genes. A prognostic risk model based on the miR-34 target genes was constructed using univariate Cox and LASSO regression analyses. Quantitative real-time PCR (qPCR) and dual-luciferase reporter assays were conducted to validate whether the target genes bind to miR-34 and measure their RNA expression levels in the relevant tumors. Additionally, the risk score was integrated with other clinical indicators to develop a nomogram prediction model for patient survival. ResultsA total of 65 target genes of the miR-34 family were screened. The cancer type exhibiting stronger correlation between the target gene scores and OS was lung adenocarcinoma (P = 0.003, HR= 5.150). Furthermore, miR-34 target genes were predominantly enriched in oxidative stress pathways and various tumor-related processes. Three genes, LDHA, GALNT7, and SATB2, were identified as core components of the prognostic analysis model for lung adenocarcinoma. Additionally, the constructed nomogram model demonstrated robust predictive performance. ConclusionThe risk model and prognosis model of lung adenocarcinoma constructed based on the key target genes of miR-34 have good predictive performance.
3.Comparison of dosimetry and radiobiology between volumetric modulated arc therapy and helical tomotherapy for craniospinal irradiation
Yongqing GE ; Xiunan WANG ; Hui YANG ; Xiaofeng MU
Chinese Journal of Radiological Health 2026;35(1):113-119
Objective To compare the dosimetric and radiobiological differences of helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) in craniospinal irradiation. Methods The CT images of 15 patients who received craniospinal irradiation in our hospital were selected. The target volumes and organs at risk (OARs) were contoured, and HT and VMAT plans were designed. The dosimetric parameters of the two plans were compared. A Matlab program based on equivalent uniform dose was developed to calculate the normal tissue complication probability (NTCP). The NTCP values of the two plans were compared. Results The homogeneity index of the target volume in the HT group was better than that in the VMAT group, with values of 0.06 ± 0.01 and 0.08 ± 0.24, respectively, and the difference was statistically significant (P=0.03). However, there was no significant difference in the conformity index of the target volume (P>0.05). There were significant differences in key indicators (Dmean, V5, Dmax) of the lungs, liver, lens, and eyeballs between the two groups (P<0.05). Regarding OARs, the NTCP values of the lens, optic chiasm, lungs, and liver in the HT and VMAT groups were as follows: 0.04 ± 0.03 vs. 0.1 ± 0.06 in the left lens, 0.04 ± 0.06 vs. 0.1 ± 0.07 in the right lens, 0.16 (0.14-0.17) vs. 0.21 (0.18-0.24) in the optic chiasm, 3.89 × 10−4 (2.45 × 10−4-7.3 × 10−4) vs. 8.95 × 10−4 (5.19 × 10−4-1.75 × 10−3) in the lungs, and 3.45 × 10−8 (6.0 × 10−9-1.036 × 10−7) vs. 9.54 × 10−8 (1.70 × 10−8-2.056 × 10−7) in the liver; the HT group was superior to the VMAT group, and all differences were statistically significant (P<0.05). The NTCP values of the heart in the two groups were 1.35 × 10−8 (6.34 × 10−9-2.06 × 10−9) vs. 5.06 × 10−9 (2.29 × 10−9-7.9 × 10−9), significantly lower in the VMAT group than in the HT group (P<0.05). Conclusion HT has high homogeneity and consistency. The two plans have their own advantages in OAR protection. For OARs with no significant differences in physical dosimetry, NTCP results can be used as a reference. Therefore, comparing the dosimetric parameters and OAR NTCP of HT and VMAT plans can help select the optimal clinical treatment strategy.
4.Mechanism of Zuogui Jiangtang Jieyu Prescription Against Damage to Hippocampal Synaptic Microenvironment via Suppressing GluR2/Parkin Signal-mediated Mitophagy in Rats with Diabetes-related Depression
Jian LIU ; Lin LIU ; Xiaoyuan LIN ; Wei LI ; Yuhong WANG ; Hui YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):104-112
ObjectiveTo reveal the mechanism of Zuogui Jiangtang Jieyu prescription against damage to hippocampal synaptic microenvironment via suppressing glutamate receptor 2 (GluR2)/Parkin signal-mediated mitophagy in rats with diabetes-related depression (DD). MethodsEighty male SD rats underwent adaptive feeding for 5 days before the study. Ten rats were randomly assigned to the normal group. The model of DD rats was established with the rest by 2-week high-fat diet + streptozotocin (STZ) tail intravenous injection + 28 days of chronic unpredictable mild stress (CUMS) combined with isolation. The rats were randomly divided into a normal group, a model group, a GluR2 blocker group (5 μg·kg-1), a GluR2 agonist group (10 μg·kg-1), a metformin + fluoxetine group (0.18 g·kg-1 metformin + 1.8 mg·kg-1 fluoxetine), and high- and low-dose Zuogui Jiangtang Jieyu prescription groups (20.52 and 10.26 g·kg-1, respectively). The rats in the GluR2 blocker group and the GluR2 agonist group were continuously injected with CNQX and Cl-HIBO in the dentate gyrus of the hippocampus once a week starting from stress modeling, respectively, while the metformin + fluoxetine group and the high- and low-dose Zuogui Jiangtang Jieyu prescription groups were continuously given intragastric administration for 28 d at the same time of stress modeling. Depression-like behavior was evaluated by open field and forced swimming experiments. The levels of serum insulin and adenosine triphosphate (ATP) in hippocampus were detected by biochemical analysis. The levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The autophagosomes of hippocampal neurons were observed by transmission electron microscopy. The morphology and structure of dendrites and spines of hippocampal neurons were evaluated by Golgi staining. Western blot detected the expression levels of GluR2 and Parkin proteins in hippocampus. The expression levels of GluR2, Parkin, regulating synaptic membrane exocytosis protein 3 (RIMS3), and postsynaptic density protein 95 (PSD95) in the dentate gyrus of the hippocampus were detected by immunofluorescence. ResultsCompared with the normal group, the model group exhibited reduced total activity distance in the open field and increased immobility time in forced swimming (P<0.01), lowered levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.01), increased autophagosomes of hippocampal neurons, significantly damaged morphology and structure of dendrites and spines of hippocampal neurons, decreased expression levels of GluR2, RIMS3, and PSD95 in hippocampus, and an increased Parkin expression level (P<0.05, P<0.01). Compared with the model group, the GluR2 blocker group and the GluR2 agonist group showed aggravation and alleviation of the above abnormal changes, respectively (P<0.05, P<0.01). The above depression-like behavior was significantly improved in the high- and low-dose Zuogui Jiangtang Jieyu prescription groups to different degrees. Specifically, the two groups saw elevated levels of serum insulin and ATP, 5-HT, and DA in hippocampus (P<0.05, P<0.01), restrained increase in autophagosomes and damage to morphology and structure of dendrites and spines of hippocampal neurons, up-regulated protein expression levels of GluR2, RIMS3, and PSD95, and down-regulated Parkin expression level (P<0.05, P<0.01). ConclusionZuogui Jiangtong Jieyu prescription can ameliorate the mitophagy-mediated damage to hippocampal synaptic microenvironment in DD rats, the mechanism of which might be related to the regulation of GluR2/Parkin signaling pathway.
5.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
6.Herbal Textual Research on Dioscoreae Hypoglaucae Rhizoma, Dioscoreae Spongiosae Rhizoma, Smilacis Chinae Rhizoma and Smilacis Glabrae Rhizoma in Famous Classical Formulas
Li LU ; Yichen YANG ; Erhuan WANG ; Hui CHANG ; Li AN ; Shibao WANG ; Cunde MA ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):218-247
This article systematically reviews and verifies the medicinal materials of Dioscoreae Hypoglaucae Rhizoma(DHR), Dioscoreae Spongiosae Rhizoma(DSR), Smilacis Chinae Rhizoma(SCR) and Smilacis Glabrae Rhizoma(SGR) from the aspects of name, origin, producing area, quality, harvesting, processing and efficacy by consulting historical literature, in order to provide reference for the development and utilization of famous classical formulas containing the four medicinal materials. DHR, DSR, SCR and SGR have a long history of application as medicinal materials. However, due to their similar growth environment and medicinal properties, as well as their functions of promoting dampness, dispelling wind and removing numbness, there have been instances of homonymous foreign objects and homonymous synonyms throughout history, resulting in confusion of the origin. Therefore, it is necessary to conduct comparative analysis and systematic research for clarifying the historical development and changes of the four, in order to provide a basis for safe and effective medication. According to research, Bixie was first recorded in Shennong Bencaojing and has been historically known as Baizhi, Chijie, Zhumu, and other aliases. From ancient times to the mid-20th century, there has always been a situation where the rhizomes of Dioscorea plants and Smilax plants, and even the rhizomes of Heterosmilax plants, were mixed together to be used as medicinal herbs for Bixie. However, since the Tang dynasty, it has been clearly advocated that the rhizomes of Dioscorea plants have excellent quality and have been the mainstream throughout history. The 2020 edition of Chinese Pharmacopoeia categorized it into two types of medicinal herbs(DHR and DSR). Among them, the origin of DHR is the dry rhizomes of Dioscorea hypoglauca, and the origins of DSR are the dry rhizomes of D. spongiosa and D. futschauensis. In ancient times, due to different types, the corresponding production areas of DHR and DSR were also different. Nowadays, They are mainly produced in the southern region of the Yangtze River. Since the Tang dynasty, the quality of Bixie has been characterized by its white color and soft nature. In modern times, it has been summarized that those with white color, large and thin pieces, powdery texture, tough and elastic texture, and neat and unbreakable are the best. The harvesting times of DHR and DSR are in spring or autumn, with the best quality harvested in autumn. The mainstream processing methods of them are slicing and then using the raw products or wine-processed products. SCR was first recorded in Mingyi Bielu and has been known as Jinganggen, Tielingjiao, Tieshuazi, and other aliases in history. The mainstream source is the dry rhizomes of Smilax china in the past dynasties, with the best quality being those that are tough and rich in powder. The harvesting time is from the late autumn to the following spring, and the main processing method throughout history has been slicing for raw use. SGR was first recorded under the item of Yuyuliang in Variorum of Shennong's Classic of Materia Medica. It was listed as an independent medicinal material from Bencao Gangmu. In history, there were such aliases as Cao Yuyuliang, Lengfantuan, Xianyiliang, Tubixie, etc. The main source of the past dynasties was dry rhizomes of S. glabra. In history, there have also been instances of multiple plants belonging to the same genus, and even cases of mixing the rhizomes of plants in the genus Heterosmilax. It is mainly produced in Guangdong, Hunan, Hubei, Zhejiang, Sichuan, Anhui and other regions, its quality has been summarized as large in size, powdery in texture, with few veins, and light brown in cross-section since modern times. The harvesting time is in spring or autumn, and the main processing method throughout history has been slicing for raw use. DHR, DSR, SCR and SGR all have the effects of promoting dampness, dispelling wind, relieving rheumatism and detoxifying. However, their detoxification abilities are ranked as follows:SGR>SCR>Bixie(DHR and DSR). Especially for the treatment of limb spasms, arthralgia and myalgia, scrofula, and scabies caused by syphilis and mercury poisoning, SGR has a unique effect. Based on the research results, DHR is recommended to develop the famous classical formulas containing Bixie as the first choice for medicinal herbs. It should be harvested in autumn, sliced thinly while fresh, and processed according to the requirements of the famous classical formulas, without any requirements for raw use. Selecting the rhizomes of S. china, harvested in late autumn, and thinly sliced while fresh. If there are no special processing requirements in the formulas, use it raw. Selecting the rhizomes of S. glabra, it is harvested in autumn and thinly sliced while fresh. If there are no special processing requirements in the formulas, raw products can be used.
7.Pharmaceutical care for a patient with empagliflozin-induced euglycemic diabetic ketoacidosis
Lili YANG ; Qi LI ; Hui WANG ; Ruilong GAO ; Min MAO
China Pharmacy 2025;36(2):214-218
OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus (T2DM) and limb-girdle muscular dystrophy (LGMD) who developed euglycemic diabetic ketoacidosis (euDKA) after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions, clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA, clinical pharmacists suggested discontinuing empagliflozin and metformin, and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis, blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors (SGLT2i). RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment, the patient’s condition improved, and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i, and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin, adjusting medication regimens,conducting pharmaceutical monitoring,and other pharmaceutical services. Meanwhile, they provide medication education to patients to ensure their medication safety.
8.Pharmaceutical care for a patient with empagliflozin-induced euglycemic diabetic ketoacidosis
Lili YANG ; Qi LI ; Hui WANG ; Ruilong GAO ; Min MAO
China Pharmacy 2025;36(2):214-218
OBJECTIVE To provide a reference for the pharmaceutical care of a patient with type 2 diabetes mellitus (T2DM) and limb-girdle muscular dystrophy (LGMD) who developed euglycemic diabetic ketoacidosis (euDKA) after taking empagliflozin. METHODS Clinical pharmacists provided pharmaceutical care for a patient with T2DM and LGMD who developed euDKA after taking empagliflozin. According to the patient’s recent use of medications and his conditions, clinical pharmacists assessed the correlation between euDKA and empagliflozin as “very likely”. As to euDKA, clinical pharmacists suggested discontinuing empagliflozin and metformin, and giving intravenous infusion of 10% Glucose injection instead of 5% Glucose injection for fluid resuscitation. Clinical pharmacists monitored the patient’s laboratory indicators such as arterial blood gas analysis, blood/urine ketones and electrolytes. They assisted physicians to decide when to stop intravenous supplements of liquid and insulin. Clinical pharmacists also assisted physicians to adjust the antidiabetic drugs and educated the patient to avoid empagliflozin or other sodium- glucose linked transporter 2 inhibitors (SGLT2i). RESULTS Physicians adopted the suggestions of clinical pharmacists. After treatment, the patient’s condition improved, and he was allowed to be discharged with medication. CONCLUSIONS euDKA is a relatively rare and serious adverse reaction associated with SGLT2i, and the patients with LGMD are susceptible to euDKA. Clinical pharmacists assist physicians in developing personalized medication plans by evaluating the association between euDKA and empagliflozin, adjusting medication regimens,conducting pharmaceutical monitoring,and other pharmaceutical services. Meanwhile, they provide medication education to patients to ensure their medication safety.
9.Increased CT Attenuation of Pericolic Adipose Tissue as a Noninvasive Marker of Disease Severity in Ulcerative Colitis
Jun LU ; Hui XU ; Jing ZHENG ; Tianxin CHENG ; Xinjun HAN ; Yuxin WANG ; Xuxu MENG ; Xiaoyang LI ; Jiahui JIANG ; Xue DONG ; Xijie ZHANG ; Zhenchang WANG ; Zhenghan YANG ; Lixue XU
Korean Journal of Radiology 2025;26(5):411-421
Objective:
Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity.
Materials and Methods:
This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC).
Results:
The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85.
Conclusion
Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.
10.Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
Claudia Ha-ting TAM ; Ying WANG ; Chi Chiu WANG ; Lai Yuk YUEN ; Cadmon King-poo LIM ; Junhong LENG ; Ling WU ; Alex Chi-wai NG ; Yong HOU ; Kit Ying TSOI ; Hui WANG ; Risa OZAKI ; Albert Martin LI ; Qingqing WANG ; Juliana Chung-ngor CHAN ; Yan Chou YE ; Wing Hung TAM ; Xilin YANG ; Ronald Ching-wan MA
Diabetes & Metabolism Journal 2025;49(1):128-143
Background:
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods:
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results:
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

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