ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase （MEK）/rat sarcoma viral oncogene homolog （Ras）/rapidly accelerated fibrosarcoma kinase （Raf）/extracellular signal-regulated kinase （ERK） signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice （eight weeks old， half male and half female） were used in the experiment. Ten mice were randomly selected as the blank control group， while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride （BAC） into the eyes for four weeks to establish a dry eye mouse model. After successful modeling， the mice were randomly divided into five groups： Model group， sodium hyaluronate group， and Mimenghua prescription groups with low dose （4.83 g·kg^-1）， medium dose （9.67 g·kg^-1）， and high dose （19.34 g·kg^-1）. The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume， tear film break-up time （TBUT）， and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration， mice were euthanized， and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin （HE） staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK， Ras， Raf， and ERK. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents and expressions of MEK， Ras， Raf， ERK， and interleukin （IL）-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to determine mRNA expression levels of MEK， Ras， Raf， and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume （P<0.05） and prolonged TBUT （P<0.05） after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK， Ras， Raf， and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose （P<0.05）. ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）. Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group （P<0.05）， but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups （P<0.05）， suggesting that Mimenghua prescription can decrease the expressions of MEK， Ras， Raf， and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses， increase tear secretion， prolong TBUT， and promote corneal recovery by inhibiting the MEK， Ras， Raf， and ERK signaling pathways in lacrimal gland and corneal tissues.

Objective: To understand the awareness of chikungunya fever knowledge and its related factors among medical college students in Baise City, so as to provide a scientific basis to offer relevant courses and special education. Methods: From July to August 2025, 7 286 enrolled medical students were selected by a sampling method from a medical college in Baise City to participate in the questionnaire survey. The questionnaire covered epidemiological characteristics, clinical symptoms, and prevention/control knowledge of chikungunya fever. Statistical analyses including the Chi quare test and multivariate Logistic regression models were performed. Results: The overall awareness rate of chikungunya fever knowledge among the medical students was 18.89%. Among the knowledge items, the awareness rate of "the high incidence season" was the highest (84.05%), while that of "the infectious period" was the lowest (17.80%). Multivariate Logistic regression analysis showed that medical students with female (a OR= 1.37 , 95%CI =1.20- 1.57 ), the age for over 25 years old (a OR=1.76, 95%CI =1.05-2.93), whose father had a middle school educational level (a OR=1.18, 95%CI =1.05-1.31), and majored in preventive medicine (a OR=1.54, 95%CI =1.10-1.67) had relatively higher awareness rates of chikungunya fever knowledge (all P <0.05). In contrast, students of Zhuang ethnicity (a OR= 0.87 , 95%CI =0.76-0.98) and majoring in nursing (a OR=0.74, 95%CI =0.61-0.91) or pharmacy (a OR=0.70, 95%CI =0.52-0.95) had relatively lower awareness rates (all P <0.05). Conclusions The awareness rate of chikungunya fever related knowledge among medical college students in Baise City is relatively low. Schools should take targeted publicity measures to improve medical students awareness.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Introduction: Large, rapidly enlarging adrenal masses typically mandate surgical intervention given the high probability of adrenocortical carcinoma (ACC). However, benign processes can mimic these aggressive growth kinetics, creating a diagnostic challenge for clinicians. Case: A 74-year-old male with hypertension, atrial fibrillation on rivaroxaban, and prostate cancer was referred for evaluation of a right adrenal incidentaloma detected on computed tomography imaging performed for prostate cancer staging. The well-defined mass measured 8.9 × 7.8 × 7.5 cm (AP × W × CC) with areas of calcification. Mean attenuation was +40 Hounsfield Unit, with no significant washout. Biochemical evaluation confirmed a non-functioning lesion (24-hour urine metanephrines 756 mcg/24 hours [N 246–753 mcg/24 hours]; serum cortisol 62 nmol/L post overnight dexamethasone suppression test). The patient was otherwise asymptomatic and declined surgical intervention. Repeat imaging 4 months later demonstrated interval enlargement of the mass to 9.8 × 8.8 × 10.7 cm. Due to this rapid growth, which was highly concerning for ACC, the patient underwent laparoscopic right adrenalectomy. Histopathological examination unexpectedly revealed an adrenal hematoma without evidence of an underlying tumor or malignancy. This case illustrates the difficulty in differentiating aggressive cortical tumors from atypical hemorrhagic events. Larger series on adrenal hemorrhage reported trauma and procedural complications as the leading causes, with a median size of 3–4 cm. Idiopathic large adrenal hematomas presenting as rapidly expanding “pseudotumors” are exceptionally rare, with fewer than 20 cases reported in which surgical resection was performed due to high preoperative suspicion of malignancy. Additionally, adrenal hemorrhage attributed to anticoagulant therapy often occurs bilaterally. Unilateral lesion, especially when large, can pose a diagnostic challenge as highlighted in this case. Conclusion In patients on anticoagulation, rapid interval growth of an adrenal mass does not always equate to malignancy. Recognizing this mimicry in the era of widespread Direct Oral Anticoagulant use is essential for refining treatment decision regarding surgical intervention, as most cases exhibited a self-limiting process with spontaneous resolution.

Introduction: The increasing prevalence of diabetes represents a significant global health challenge. Modifiable risk factors, including physical inactivity, unhealthy dietary habits, and obesity contribute substantially to this rising burden. In conjunction with the 2025 World Diabetes Day (WDD) campaign focusing on “diabetes and the workplace,” we assessed diabetes risk among healthcare workers in our hospital using the Modified Asian Finnish Diabetes Risk Score (ModAsian FINDRISC). Methodology: Healthcare workers from various departments were invited to participate in the hospital WDD celebration. A total of 286 attendees underwent anthropometric measurements and completed the ModAsian FINDSRIC questionnaire. Descriptive statistics were used to summarize the prevalence of risk factors and overall diabetes risk. Results: The participants included doctors, nurses, allied healthcare professionals, as well as hospital support and administrative staff. The majority of participants (74.8%) were aged below 45 years. 39.2% were overweight while 30.8% were obese. One-third (37.4%) had increased waist circumference (WC) (≥90 cm for men, ≥80 cm for women). Additionally, 20% of respondents reported being on antihypertensive medication, and 23.8% had previously recorded high blood glucose. A family history of diabetes mellitus (DM) was reported by 62.6% of respondents. Additionally, about onethird were sedentary with less than 30 minutes of daily exercise or physical activity, another one-third did not consume fruits or vegetables on a daily basis. The median ModAsian FINDRISC score was 8, with approximately 30% of them classified as having moderate to very high risk of developing DM (moderate: 17.5%; high: 10.8%; very high: 2.8%). Conclusion These results revealed high metabolic risk in healthcare workers and highlight the need for targeted workplace health promotion strategies to reduce the risk of developing diabetes.
Tertiary Care Centers ; Health Personnel ; Diabetes Mellitus

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

Introduction: Repaglinide, a meglitinide analogue, has a rapid onset and short duration of action. It offers prandial glucose control while reducing hypoglycemia risk compared to sulfonylureas. We describe its use in our special cohorts of diabetic patients where repaglinide was prescribed to reduce hypoglycemia in vulnerable patients or to optimize glycemic control through pharmacotherapy intensification or deintensification. Cases: Cohort A comprised 12 elderly patients with multiple comorbidities (mean age: 70.3 years; mean DM duration: 18.3 years) characterized by high glucose variability and problematic hypoglycemia. In seven patients, low-dose gliclazide was replaced with repaglinide with reduction in hypoglycemic episodes. One patient on low-dose premixed insulin was successfully switched to preprandial repaglinide. Two patients on basal insulin were able to reduce their insulin requirements and stabilize their glucose levels. A younger patient with autonomic dysfunction had hypoglycemia while on insulin glulisine, while its omission led to severe hyperglycemia. Substituting glulisine with repaglinide resolved the glucose variability. Repaglinide effectively reduced hypoglycemic episodes while maintaining glycemic stability, with a mean hemoglobin A1c (HbA1c) reduction of 0.36% over 3–6 months. Cohort B consisted of six younger patients (mean age: 35.3 years) with focus on optimizing HbA1c and improving treatment adherence. Two patients on basal-bolus regimes success-fully transitioned off bolus insulin to repaglinide, significantly improving compliance. One patient on basal insulin was successfully transitioned to an all-oral regimen. Three patients on existing oral hypoglycemic agents were started on repaglinide to close the glycemic gap. Cohort B achieved a robust mean HbA1c reduction of 2.1% within 3–6 months. Conclusion Repaglinide remains an important armamentarium in personalized diabetes management. Its pharmacokinetics and flexible dosing allow intensification of glycemic control while minimizing the risk of hypoglycemia. It also offers a viable strategy for selected patients struggling with complex insulin regime.
Repaglinide

Introduction: Severe hypercalcemia is most commonly caused by primary hyperparathyroidism (PHPT) and malignancy. While standard therapies are effective in most cases, a subset of patients have persistent or refractory hypercalcemia. We present a retrospective case series detailing the clinical characteristics, biochemistry, and outcomes of patients treated with denosumab for hypercalcemia. Cases: Seven patients with severe hypercalcemia were identified, comprising five with PHPT and two with malignancyassociated hypercalcemia. The mean age was 70.4 years (range 55–86), with 71% female (n = 5) and 29% male (n = 2). Baseline corrected calcium ranged from 2.92 to 4.59 mmol/L, with a mean of 3.26 mmol/L. In the PHPT cohort, parathyroid hormone (PTH) levels were significantly elevated (16.7–168 pmol/L), while malignancy patients had suppressed PTH (0.6 and 0.9 pmol/L). Prior to denosumab, 4/7 patients (57%) received bisphosphonates, 3/7 (43%) received calcitonin, and 1/7 (14%) was treated with cinacalcet. Denosumab resulted in a mean reduction in corrected calcium of 0.22 mmol/L from 3.26 to 3.03 mmol/L. Biochemical response was observed in 5/7 patients (71%). Of these, 3 patients (43%) achieved normocalcemia, while 2 patients (29%) demonstrated a partial response. The remaining 2/7 patients (29%) showed no significant improvement in calcium levels. Among responders, the mean time to calcium reduction to <3.0 mmol/L was 27 days (range 7–47). Repeat dosing was required in the majority of patients, with a mean of 1.7 doses per patient (range 1–4), indicating variability in both onset and durability of response. Among patients with PHPT, four underwent parathyroidectomy, and one declined surgery. Both patients with malignancy were managed nonsurgically. Conclusion Denosumab achieved normocalcemia in 43% of patients, with additional partial responses. Its effects were variable, with delayed response and frequent need for repeat dosing, supporting its role as an adjunctive or bridging therapy rather than as a definitive treatment.
Denosumab ; Hypercalcemia ; Retrospective Studies

Introduction: Hypercalcemic crisis, a decompensated state characterized by multiorgan dysfunction and a corrected serum calcium (CCa) level typically >3.5 mmol/L, is a rare but lifethreatening endocrine emergency that requires prompt recognition and aggressive multimodal management. We report a fatal case of hypercalcemic crisis secondary to primary hyperparathyroidism, which was refractory to multiple lines of medical therapy. Case: A 55-year-old female with diabetes mellitus, hypertension, and chronic kidney disease (creatinine 159 umol/L; estimated glomerular filtration rate 33 mL/min) presented with 3 days of confusion, profound fatigue, and constipation, preceded by a 1-month history of polyuria and polydipsia. Her Glasgow Coma Scale (GCS) was E4V3M5. Physical examination was unremarkable, with no palpable neck swelling. Significant laboratory findings included severe hypercalcemia with markedly elevated serum intact parathyroid hormone (iPTH) (CCa 4.49 mmol/L; phosphate 1.01 mmol/L; iPTH 60.1 pmol/L [N 1.6–6.0]; creatinine 149 umol/L). Saline diuresis was initiated together with subcutaneous calcitonin, resulting in an initial biochemical response, with CCa decreasing to a nadir of 3.61 mmol/L. However, the CCa subsequently rebounded to 5.00 mmol/L. Hemodialysis was performed, followed by administration of subcutaneous denosumab 60 mg. Nonetheless, the CCa decreased only modestly to 4.28 mmol/L. She became increasingly drowsy, and her clinical course was further complicated by aspiration pneumonia and lung collapse, leading to respiratory failure requiring intubation and inotropic support. Despite intensive care, additional sessions of hemodialysis and continuous renal replacement therapy, her CCa remained persistently above 4.0 mmol/L, peaking at 5.35 mmol/L. Due to her critical condition, imaging for lesion localization could not be performed. She eventually succumbed to her illness on day 10 of admission, before definitive surgery could be undertaken. Conclusion This case highlights the potentially fatal course of hypercalcemic crisis secondary to primary hyperparathyroidism. The reported mortality rate is high, at around 60%. Early recognition and intensive management, including emergency parathyroidectomy in resistant cases, have been shown to be crucial in improving outcomes.
Hyperparathyroidism, Primary

Introduction: Ectopic ACTH secretion (EAS) is a rare cause of Cushing’s syndrome, accounting for 5–15% of cases. Pulmonary neuroendocrine tumors are the most frequent cause. However, primary tumor localization remains a significant diagnostic challenge, delaying effective treatment. Case: A 59-year-old female with diabetes mellitus presented with refractory hypertension and hypokalemia. Initial laboratory findings revealed a baseline cortisol of 1,164 nmol/L and morning adrenocorticotropic hormone (ACTH) of 19.5 pmol/L (normal <10.2 pmol/L), with an overnight dexamethasone suppression test cortisol of 624 nmol/L. Pituitary magnetic resonance imaging (MRI) and computed tomography (CT) scans of the thorax, abdomen, and pelvis were initially unremarkable. A PET scan identified mild hypermetabolism in the left adrenal gland and gastrointestinal tract, though colonoscopy revealed only chronic colitis. An intravenous desmopressin stimulation test demonstrated a 181% rise in ACTH and a 35% rise in cortisol, pointing toward pituitary Cushing’s. However, repeat pituitary MRI remained normal. A high-dose dexamethasone suppression test showed approximately 34% cortisol suppression (cortisol 1,128 nmol/L to 745 nmol/L), suggesting ectopic Cushing’s syndrome. Bilateral inferior petrosal sinus sampling demonstrated a peak central-to-peripheral ACTH ratio of 1.8 on the right and 1.6 on the left, pointing toward ectopic Cushing’s. Localization with DOTATATE PET-CT identified a 7 × 9 × 8 mm nodule in the right middle lobe. A wedge resection was performed. Histopathology confirmed a typical carcinoid tumor with clear resection margins. Immunohistochemistry revealed tumor cells positive for CK AE1/ AE3, synaptophysin, chromogranin, and INSM-1, with weak positivity for ACTH. The latest 8 am cortisol was 117 nmol/L and ACTH 1.74 pmol/L, confirming biochemical cure. Hypokalemia resolved, with improvement in her metabolic profile. Conclusion This case highlights the diagnostic complexities of EAS, particularly when initial imaging is inconclusive and biochemical tests yield conflicting results. Timely, precise localization of the causative tumor is crucial for successful surgical intervention and to prevent severe complications of hypercortisolism, thereby improving patient outcomes.
ACTH Syndrome, Ectopic