1.Recurrent Diabetic Ketoacidosis: Predictors and Clinical Outcomes in a 24-Year Retrospective Cohort
Liang Wei Wong ; Lisa Mohamed Nor ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Jia Whey Jacelyn Ong ; Chin Voon Tong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):33-34
Introduction:
Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare
burden. Despite advances in diabetes care, recurrent
DKA remains common, often reflecting gaps in treatment
adherence and patient education. Identifying predictors
of recurrence is crucial for risk stratification and targeted
intervention.
Methodology:
We conducted a retrospective observational study of all
adult DKA admissions to a tertiary centre between 2001
and 2025. Electronic medical records were reviewed for
demographic data, biochemical parameters, precipitating
factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated
with recurrent DKA admissions were analyzed. Patients
under the age of 18 years and those with missing vital
information were excluded.
Results:
A total of 667 DKA admissions, comprising 566 patients,
were identified, of which 101 admissions (15.1%) were
recurrent, involving 65 patients. Among recurrent DKA
episodes, the most common precipitating factors were
infection (64.4%) and insulin omission (62.4%). After
multivariate analyses, patients with type 1 diabetes
mellitus (T1DM) were more likely to develop recurrent
DKA compared to those with type 2 diabetes mellitus
(aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001).
Insulin omission was strongly associated with recurrent
DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast,
baseline glycated hemoglobin and chronic kidney disease
were not significantly associated with recurrence. Diabetic
counseling during the first DKA admission did not reduce
recurrent DKA. There were no significant differences in
mortality (3.9% vs 6.2%, p = 0.524) or critical care admission
rates (40.6% vs 38.7%, p = 0.718) between recurrent and first
DKA episodes.
Conclusion
Recurrent DKA accounts for a substantial proportion of
DKA admissions and is strongly associated with insulin
omission and T1DM. Our findings suggest that recurrent
DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary
interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis
;
Retrospective Studies
2.Clinical and Biochemical Characteristics of Adult Diabetic Ketoacidosis: T1DM vs. T2DM
Mohd Fyzal Bahrudin ; Chin Voon Tong ; Raja Nurazni Raja Azwan ; Adilah Zulaikha Abd Latib ; idayatil Alimi Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Syaza Izhar Hisham ; Liang Wei Wong ; Jia Whey Jacelyn Ong ; Lisa Mohamed Nor ; Zanariah Hussein
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):39-40
Introduction:
The rising incidence of diabetic ketoacidosis (DKA) in type 2
diabetes mellitus (T2DM) represents a paradigm shift from
its traditional recognition as a hallmark complication of
type 1 diabetes mellitus (T1DM). However, contemporary
data comparing clinical presentation, precipitating factors,
and outcomes between these two populations remain
limited.
Methodology:
In this retrospective observational study, all adult DKA
admissions with T1DM or T2DM at a tertiary centre between
2001 and 2025 were studied. DKA was defined according
to standard biochemical criteria. Electronic medical records were reviewed to extract demographic data, biochemical
parameters, precipitating factors, management details, and
clinical outcomes of all adult DKA admission in T1DM and
T2DM. Patients aged <18 years or those with incomplete
data were excluded.
Results:
A total of 601 DKA episodes were analyzed, comprising
130 (21.6%) in patients with T1DM and 471 (78.4%) in those
with T2DM. Mean age was 26.9 ± 0.71 years for T1DM and
52.1 ± 0.7 years for T2DM. Gender distribution was balanced
(male 48.3%, female 51.7%). Mean hemoglobin A1c (HbA1c)
was 11.3 ± 0.3% in T1DM and 12.1 ± 0.2% in T2DM. Infection
was the most common precipitating factor overall (69.0%),
occurring more frequently in T2DM than in T1DM (74.7%
vs. 56.2%), followed by medication non-adherence (62.4%
vs. 43.8%). Significant differences were observed between
groups in admission pH, bicarbonate (both p <0.001), blood
ketones (p = 0.028), and HbA1c (p = 0.010), whereas anion
gap (p = 0.056) and blood glucose levels (p = 0.755) did not
differ significantly. Clinical outcomes were comparable
with respect to intensive care unit (ICU) admission rates
(40.0% in T1DM vs. 39.0% in T2DM, p = 0.779) and median
resolution time (p = 0.462). However, the median length of
hospital stay was significantly longer in T2DM (8.2 ± 0.32
vs. 5.4 ± 0.4 days; p <0.001). Overall mortality was 6.0%,
with substantially higher mortality in T2DM compared to
T1DM (7.4% vs. 0.8%, p = 0.013).
Conclusion
In this large regional series of adult DKA, most episodes
occurred in T2DM. Despite similar ICU admission rates
and time to resolution, T2DM was associated with more
frequent infection-related precipitants, longer hospital
stays, and higher mortality, underscoring the need for
targeted preventive strategies in this population.
Adult
;
Diabetes Mellitus, Type 1
;
Diabetic Ketoacidosis
;
Diabetes Mellitus, Type 2
3.Diabetic Ketoacidosis in Pregnancy: Clinical Triggers, Outcomes, and Missed Opportunities—A Case Series
Jia Whey Jacelyn Ong ; Chin Voon Tong ; Raja Nurazni binti Raja Azwan ; Adilah Zulaikha binti Abd Latib ; Hidayatil Alimi bin Keya Nordin ; Qin Zhi Lee ; Kean Heng Lim ; Jia Ling Low ; Mohd Fyzal bin Bahrudin ; Syaza binti Izhar Hisham ; Liang Wei Wong ; Lisa Mohamed Nor ; Nurain Mohd Noorr
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):48-49
Introduction:
Diabetic ketoacidosis (DKA) in pregnancy is an uncommon
yet life-threatening emergency, with disproportionate risks
to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite
this, local data remain limited. We describe the clinical
profile, precipitating factors, and outcomes of DKA in
pregnancy in a tertiary centre, with emphasis on potentially
preventable triggers.
Cases:
Nine pregnant patients with DKA were identified from a
retrospective review of all cases admitted for DKA from
2002 to 2025. Mean age was 31.67 ± 5.20 years; all were
Malay. The majority had type 2 diabetes mellitus (55.6%),
followed by type 1 diabetes (33.3%) and latent autoimmune
diabetes in adults (11.1%). The mean period of amenorrhea
was 19.67 ± 12.62 weeks.
Infection was the leading precipitant (44.4%), with
additional triggers including insulin omission (22.2%),
hyperemesis gravidarum, preterm labor, steroid exposure,
and perioperative fasting. Most diagnoses were made in
the emergency department (55.6%).
Biochemical parameters reflected significant severity (mean
bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81),
with 88.9% classified as severe DKA. Intensive Care Unit
(ICU) care was required in 77.8% of cases. The majority
(77.8%) were admitted to the ICU unit, with a median time
to resolution of 13.00 ± 12.00 hours (interquartile range
[IQR]), and the median hospital length of stay was 7.00 ±
5.00 days (IQR).
Complications during treatment included hypokalemia
(33.3%), acute kidney injury (22.2%), and hypoglycemia
(11.1%). Rebound DKA occurred in one-third of patients.
All patients were discharged clinically stable. Outcome
data demonstrated pregnancy loss in three cases and one
preterm birth.
Conclusion
DKA in pregnancy remains a severe and resource-intensive
condition. This series highlights missed opportunities in
prevention, with modifiable precipitants such as infection
and insulin omission commonly identified. The high
severity at presentation suggests delays in recognition.
Early detection, optimized metabolic care, and targeted
preventive strategies are crucial to improving maternal
and fetal outcomes.
Female
;
Pregnancy
;
Diabetic Ketoacidosis
4.Exploring Mechanism of Yijing Decoction in Treating Decreased Ovarian Reserve Based on Oxidative Stress Mediated by Chronic Iron Overload
Jing YU ; Chengcheng LIANG ; Heng HU ; Zhe LI ; Haijing CHU ; Jijun CHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(18):77-87
ObjectiveTo investigate the mechanism of Yijing decoction to inhibit oxidative stress induced by chronic iron overload and improve ovarian reserve hypofunction in mice. MethodsSeventy-two female C57BL/6J mice with normal estrous cycles were randomly divided into six groups (n=12 per group):blank group,model group,Yijing decoction(YJD) low-dose group,medium-dose group,high-dose group,and dehydroepiandrosterone (DHEA) group. Mice in the blank group received intraperitoneal injections of normal saline,while those in all other groups were administered iron dextran (Sigma-Aldrich) at a dose of 0.5 g·kg-1 once weekly for 8 weeks to establish a chronic iron overload model. Following the final injection,interventions were initiated and continued for 4 weeks. The low,medium,and high dose groups of YJD received oral gavage of Yijing decoction aqueous solution at doses of 18.165, 36.33,and 72.66 g·kg-1·d-1,respectively. The DHEA group received DHEA aqueous solution at 10.812 5 mg·kg-1·d-1. The blank and model groups received an equivalent volume of distilled water by gavage once daily. Body weight was recorded weekly,and food intake was monitored throughout the treatment period. Vaginal smears were collected daily and stained with hematoxylin-eosin (HE) to assess estrous cycle regularity. At the end of the experiment,mice were euthanized,and bilateral ovaries and uteri were rapidly excised and weighed to calculate ovarian and uterine indices (mg·g-1). Ovarian tissues were fixed,embedded,and sectioned for hematoxylin and eosin (HE) staining to evaluate histopathological changes. Iron deposition in ovarian tissue was visualized using Prussian blue staining. Serum levels of follicle-stimulating hormone (FSH),luteinizing hormone (LH),estradiol (E2),and anti-Müllerian hormone (AMH) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in ovarian homogenates were determined using commercial biochemical assay kits. Reactive oxygen species (ROS) levels in ovarian tissue were assessed by ROS fluorescence staining on frozen sections. Mitochondrial ultrastructure in ovarian tissue was examined by transmission electron microscopy (TEM). Total RNA was extracted from ovarian tissue for real-time quantitative polymerase chain reaction (Real-time PCR) to quantify mRNA expression of ferritin heavy chain 1 (Fth1),ferritin light chain (Ftl),transferrin (Tf),transferrin receptor 1 (Tfr1),catalase (Cat),and glutathione peroxidase 1 (GPX1). Protein expression levels of Fth1,Ftl,Tf,Tfr1,and glutathione peroxidase 4 (GPX4) were analyzed by Western blot. ResultsCompared with the blank group,mice in the model group exhibited significantly reduced body weight and severe estrous cycle disruption (P<0.01),a markedly increased uterine index (P<0.01),and a significantly decreased ovarian index (P<0.01). The number of antral follicles was significantly reduced,while atretic follicles were markedly increased,accompanied by pronounced iron deposition in the ovarian stroma. Serum levels of AMH and E2,as well as ovarian SOD activity,protein and mRNA expression of Tf and Tfr1,and mRNA levels of GPX1 and Cat were all significantly downregulated (P<0.05,P<0.01). Conversely,serum FSH and LH levels,MDA content,protein and mRNA expression of Fth1 and Ftl,and ROS fluorescence intensity were significantly elevated (P<0.05,P<0.01),along with a marked decrease in GPX4 protein expression (P<0.01). TEM revealed an increased number of damaged mitochondria in ovarian tissue,characterized by loss or disappearance of mitochondrial cristae. Compared with the model group,treatment with low,medium,and high doses of YJD and DHEA significantly improved body weight and ameliorated estrous cycle irregularities (P<0.05,P<0.01),decreased the uterine index (P<0.05),and increased the ovarian index (P<0.05,P<0.01). These groups also showed increased numbers of antral follicles,reduced atretic follicles,and significantly diminished iron deposition in the ovarian stroma. Serum AMH and E2 levels,ovarian SOD activity,protein and mRNA expression of Tf and Tfr1,and mRNA levels of GPX1 and Cat were all significantly upregulated (P<0.05,P<0.01). In contrast,serum FSH and LH levels,MDA content,protein and mRNA expression of Fth1 and Ftl,and ROS fluorescence intensity were significantly reduced (P<0.05,P<0.01),while GPX4 protein expression was markedly increased (P<0.01). Moreover,mitochondrial damage was alleviated,and mitochondrial ultrastructure was notably restored in ovarian tissue. ConclusionYijing decoction ameliorates ovarian reserve function in mice with chronic iron overload by upregulating the expression of Tf,Tfr1,and GPX4,downregulating the expression of Ft,Fth1,and Ftl,thereby alleviating systemic iron metabolism disorders,reducing oxidative stress in ovarian tissue,and restoring mitochondrial morphology and structure.
5.Study on secondary metabolites of Penicillium expansum GY618 and their tyrosinase inhibitory activities
Fei-yu YIN ; Sheng LIANG ; Qian-heng ZHU ; Feng-hua YUAN ; Hao HUANG ; Hui-ling WEN
Acta Pharmaceutica Sinica 2025;60(2):427-433
Twelve compounds were isolated from the rice fermentation extracts of
6.Yijingtang Reduces Ovarian Inflammatory Responses in Rat Model of Diminished Ovarian Reserve via TLR4/MyD88/NF-κB Signaling Pathway
Heng HU ; Jijun CHU ; Zhe LI ; Haijing CHU ; Jing YU ; Chengcheng LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):20-30
ObjectiveTo investigate the effect and mechanism of Yijingtang (YJT) in treating diminished ovarian reserve (DOR) in rats by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank, model, low- and high-dose (12.579 and 25.158 g·kg-1, respectively) YJT, and dehydroepiandrosterone (7.487 5 mg·kg-1) groups, with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension (5 mg·kg-1) by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days, and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH)] and inflammatory factors [tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-10 (IL-10)] were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction(Real-time PCR) was conducted to determine the mRNA levels of TLR4, MyD88, NF-κB profilin α (IκBα), NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence (IF) was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group, the model group showed disturbed estrous cycles, increased inflammatory infiltration in the ovarian tissue, decreases in ovarian index and proportion of presinusoidal follicles, and an increase in the proportion of atretic follicles (P<0.05, P<0.01). In addition, the model group showed elevated serum levels of FSH, LH, TNF-α, and IL-1β, up-regulated mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.01), lowered serum levels of AMH, E2, and IL-10, down-regulated mRNA level of IL-10 (P<0.01), and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group, dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle, reduced inflammatory infiltration in the ovarian tissue, increased the ovarian index (P<0.01), and changed the follicular composition ratio (P<0.01). Furthermore, the drugs lowered the serum levels of FSH, LH, TNF-α, and IL-1β, down-regulated the mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and the protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.05, P<0.01), raised the serum levels of AMH, E2, and IL-10, up-regulated the mRNA level of IL-10 (P<0.05, P<0.01), and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue, thereby improving the ovarian function in DOR rats.
7.Yijingtang Reduces Ovarian Inflammatory Responses in Rat Model of Diminished Ovarian Reserve via TLR4/MyD88/NF-κB Signaling Pathway
Heng HU ; Jijun CHU ; Zhe LI ; Haijing CHU ; Jing YU ; Chengcheng LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):20-30
ObjectiveTo investigate the effect and mechanism of Yijingtang (YJT) in treating diminished ovarian reserve (DOR) in rats by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank, model, low- and high-dose (12.579 and 25.158 g·kg-1, respectively) YJT, and dehydroepiandrosterone (7.487 5 mg·kg-1) groups, with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension (5 mg·kg-1) by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days, and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH)] and inflammatory factors [tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-10 (IL-10)] were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction(Real-time PCR) was conducted to determine the mRNA levels of TLR4, MyD88, NF-κB profilin α (IκBα), NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence (IF) was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group, the model group showed disturbed estrous cycles, increased inflammatory infiltration in the ovarian tissue, decreases in ovarian index and proportion of presinusoidal follicles, and an increase in the proportion of atretic follicles (P<0.05, P<0.01). In addition, the model group showed elevated serum levels of FSH, LH, TNF-α, and IL-1β, up-regulated mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.01), lowered serum levels of AMH, E2, and IL-10, down-regulated mRNA level of IL-10 (P<0.01), and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group, dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle, reduced inflammatory infiltration in the ovarian tissue, increased the ovarian index (P<0.01), and changed the follicular composition ratio (P<0.01). Furthermore, the drugs lowered the serum levels of FSH, LH, TNF-α, and IL-1β, down-regulated the mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and the protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.05, P<0.01), raised the serum levels of AMH, E2, and IL-10, up-regulated the mRNA level of IL-10 (P<0.05, P<0.01), and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue, thereby improving the ovarian function in DOR rats.
8.Three-dimensional speckle tracking imaging in evaluation on right ventricular function for predicting adverse events in patients with unstable angina after PCI
Wenshu HU ; Chang ZHOU ; Liang XU ; Heng SUN ; Shuting NIE ; Yuanyuan SHAO ; Xinyi LI
Chinese Journal of Interventional Imaging and Therapy 2025;22(2):102-106
Objective To observe the value of three-dimensional speckle tracking imaging(3D-STI)in evaluation on right ventricle(RV)function for predicting adverse events in patients with unstable angina(UA)after percutaneous coronary intervention(PCI).Methods A total of 155 UA patients who underwent both 3D-STI and conventional echocardiography and planned to accept PCI were prospectively enrolled and divided into adverse event group(n=37)and control group(n=118)based on the occurrence of adverse events after PCI or not.Clinical data and echocardiographic parameters were compared between groups,and new binary variables were generated according to the optimal cut-off values showed by the maximum Youden index of receiver operating characteristic curves of 3D-STI parameters being statistically different between groups.Then the independent predictors of adverse events among UA patients after PCI were analyzed,a combined model was constructed,and its predictive value was assessed.Results In adverse event group,the left ventricular end diastolic volume(LVEDV)was higher,while the left ventricular ejection fraction(LVEF),right ventricular free wall longitudinal strain(RVFWLS)and right ventricular global longitudinal strain(RVGLS)were all lower than those in control group(all P<0.05).The optimal cut-off values for distinguishing adverse event or not was 110 ml for LVEDV,19.05%for RVFWLS and 19.75%for RVGLS,respectively,and all the 3 generated binary variables were independent predictors for adverse events of UA patients after PCI(all P<0.05).The area under the curve of combined model for predicting adverse events in UA patients after PCI was 0.864.Conclusion RVFWLS<19.05%and RVGLS<19.75%obtained with 3D-STI,as well as LVEDV>110 ml with conventional echocardiography were all independent predictors of adverse events in UA patients after PCI.
9.Effects of Bushen Antai Mixture on Maternal and Foetal Interface Angiogenesis in Recurrent Spontaneous Abortion Mice Based on the VEGF/Hippo/YAP Pathway
Zhe LI ; Chengcheng LIANG ; Haijing CHU ; Heng HU ; Jing YU ; Jijun CHU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):107-112
Objective To observe the effects of Bushen Antai Mixture on angiogenesis at the maternal fetal interface in recurrent spontaneous abortion(RSA)mice;To explore its mechanism in treating RSA based on the VEGF/Hippo/YAP pathway.Methods RSA mouse model and normal pregnancy mouse were constructed using Clark classic method.RSA model mice were randomly divided into model group,progesterone group,Bushen Antai Mixture low-,medium-and high-dosage groups,and normal pregnant mice were used as normal group,with 10 mice in each group.Starting from the first day of pregnancy,each medication group was given the corresponding medication by gavage for 15 days.The absorption rate of mouse embryos was calculated,the morphology of decidual tissue were observed by HE staining,the mRNA and protein expression of VEGF and Hippo/YAP pathway-related molecules of decidual tissue were detected by RT-qPCR and Western blot.Results Compared with the normal group,the absorption rate of embryos in the model group significantly increased(P<0.01),the arrangement of decidual tissue cells were disordered,edematous and degenerated,some nuclei disappeared,the vascular density decreased,the mRNA expressions of VEGF,Yes associated protein(YAP),large tumor suppressor factor(LATS)1 and LATS2 in decidual tissue significantly decreased(P<0.01),the protein expression of VEGF decreased(P<0.01),and the protein expressions of p-YAP/YAP and p-LATS/LATS significantly increased(P<0.01).Compared with the model group,the absorption rate of embryos in each dosage group of Bushen Antai Mixture was significantly reduced(P<0.05,P<0.01),the cells in the decidual tissue were arranged in an orderly manner,and edema degeneration was reduced,the mRNA expressions of VEGF,YAP,LATS1 and LATS2 in decidual tissue significantly increased(P<0.05,P<0.01),and the protein expression of VEGF significantly increased(P<0.05,P<0.01),the protein expressions of p-YAP/YAP and p-LATS/LATS decreased(P<0.05,P<0.01).Conclusion Bushen Antai Mixture can promote the expressions of VEGF,YAP,LATS by activating VEGF/Hippo/YAP signaling pathway,promote angiogenesis at the maternal-fetal interface,reduce the pregnancy loss rate,and play a therapeutic effect of RSA.
10.The impact of coexisting choroidal detachment on surgical prognosis in macular hole retinal detachment associated with high myopia
Yi CAI ; Mingwei ZHAO ; Jianhong LIANG ; Hong YIN ; Wenzhen YU ; Xuan SHI ; Jinfeng QU ; Yong CHENG ; Jing HOU ; Heng MIAO ; Enzhong JIN
Chinese Journal of Ocular Fundus Diseases 2025;41(2):89-97
Objective:To investigate the clinical characteristics of patients with high-myopia macular hole retinal detachment (MHRD) combined with choroidal detachment and to preliminarily analyze factors associated with postoperative hole closure.Methods:A retrospective clinical case series study. A total of 68 patients with high myopia (68 eyes) with MHRD diagnosed by Department of Ophthalmology, Peking University People’s Hospital from January 2019 to April 2024 were included in this study. Among them, there were 14 males (14 eyes) and 54 females (54 eyes). The mean age was (61.10±9.66) years. All eyes were treated with pars plana vitrectomy (PPV) combined with silicone oil or gas filling. Best corrected visual acuity (BCVA), intraocular pressure, and B-mode ultrasonography were performed. The BCVA test was performed using the Snellen visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The range of choroidal detachment was defined according to the number of involved quadrants observed in B-mode ultrasound or surgery, which was divided into 1 to 4 quadrants. Axial length (AL) was measured under retinal reattachment. In 68 eyes, there were 17 eyes with choroidal detachment and 51 eyes without choroidal detachment, respectively. There were 17 eyes with choroidal detachment, and the detachment range involved 1, 2, 2 and 12 eyes in 1, 2, 3 and 4 quadrants, respectively. During operation, 13% C 3F 8 was filled in 2 eyes, all of which were not complicated with choroidal detachment. 66 eyes were filled with silicone oil. According to whether the patients were complicated with choroidal detachment, the patients were divided into the group without choroidal detachment and the group with choroidal detachment. Independent sample t test, Welch two-sample t test or Mann-Whitney U test were used for comparison between groups. Generalized linear regression and logistic regression were used to analyze the relationship between the aperture size of postoperative unclosed holes and the closed hole after surgery and clinical factors. Results:At 3 months after surgery, the logMAR BCVA of the affected eye was 1.29±0.43, with a preoperative to postoperative difference ranging from -1.60 to 0.70 (-0.51±0.51) logMAR units. The AL ranged from 26.6 to 34.3 (29.60±2.12) mm. Among 68 eyes, macular hole of 37 (54.4%, 37/68) eyes were open and 31 (45.6%, 31/68) eyes were closed, respectively. The hole diameter of the open eye was (753±424) μm. There was no significant difference in age, course of disease and AL between the two groups ( W=412.0, 477.5, 427.0; P>0.05). Before operation, BCVA in patients with choroidal detachment was worse ( W=257.5) and intraocular pressure was lower ( t=4.051) in patients with choroidal detachment compared with those without choroidal detachment, with statistical significance ( P<0.05). At 3 months after surgery, BCVA in patients with choroidal detachment was significantly worse than that in patients without choroidal detachment, with statistical significance ( W=284.0, P<0.05). There were no significant differences in logMAR BCVA difference ( t=0.616) and macular hole closure rate ( χ 2=0.000) before and after surgery ( P>0.05). The reoperation rate of retinal detachment due to persistent or recurrent retinal detachment was significantly higher in the group with choroid detachment than in the group without choroid detachment, and the difference was statistically significant (odds ratio=6.424, P<0.05). Logistic regression analysis showed that young age was significantly correlated with macular hole closure failure after surgery ( β=0.077, P=0.015). There was no correlation between AL, duration of disease, BCVA before surgery, intraocular pressure, wether combined with choroid detachment range and postoperative hole closure ( β=-0.072, 0.000, 0.672, -0.085, -0.391; P>0.05). Conclusions:Concomitant choroidal detachment adversely affected on both pre-operative and post-operative visual acuity in high myopia MHRD. It is closely associated with the risk of recurrent retinal detachment and the needs of multiple operations, but has no significant effect on hole closure rate. Lower age of onset may be a risk factor for macular hole closure.


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