The therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with intestinal probiotics on the wound healing of diabetic mice and its potential mechanism were explored. A diabetic wound mouse model was established, and 25 male C57BL/6J mice were randomly divided into five groups: blank control group, model group, hUCMSCs treatment group, probiotics treatment group, and hUCMSCs combined with probiotics treatment group. The wound healing conditions were photographed and recorded on days 0, 3, 6, 9, and 12 after modeling, and the differences in wound healing rates among the groups were analyzed. HE and Masson staining were used to observe the histopathological changes and collagen deposition. CD31 immunofluorescence was used to detect angiogenesis. Collagen I immunohistochemistry was used to evaluate the formation of type I collagen. ELISA was used to detect the expression levels of anti-inflammatory factors (Arg1) and pro-inflammatory factors (IL-6, IL-1β, TNF-α) in wounded skin tissue and serum. The results showed that on day 12 after modeling, compared with the other groups, the combined treatment group had the most significant wound contraction and the fastest healing rate. HE and Masson staining showed that the combined treatment group had the fastest epithelialization and the most collagen deposition. Immunofluorescence and immunohistochemistry showed that the combined treatment group had the highest expression levels of CD31 and Collagen I. ELISA results indicated that the combined treatment group had higher expression levels of Arg1 in wound skin tissue and serum than the other groups, while the expression levels of IL-6, IL-1β, and TNF-α were significantly lower. These results suggest that the combined treatment of hUCMSCs and intestinal probiotics can accelerate wound healing in diabetic mice through mechanisms such as promoting angiogenesis, enhancing collagen deposition, and regulating the inflammatory microenvironment. The therapeutic effect was significantly better than that of single treatment, providing a new potential strategy for the clinical treatment of diabetic foot.

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.

Lung cancer is the leading cause of cancer-related deaths worldwide， and tumor metastasis is a key factor contributing to the mortality of most lung cancer patients. Aberrant activation of epithelial-mesenchymal transition （EMT） is a major driver of lung cancer progression and metastasis. EMT is characterized by the loss of apical-basal polarity and intercellular adhesion in highly differentiated， polarized， and organized epithelial cells， which acquire motility， migratory potential， and invasive properties. During this process， cells undergo cytoskeletal remodeling and transform into a mesenchymal phenotype， accompanied by associated changes in cellular markers. The EMT process is highly complex and is tightly regulated by intricate networks involving multiple transcription factors， post-translational controls， epigenetic modifications， and non-coding RNAs. Therefore， therapies targeting the mechanisms of malignant transformation and their associated pathways in lung cancer are of significant clinical importance. In recent years， EMT has attracted increasing attention as a potential target for cancer therapy. Chinese medicine， with its characteristics of multi-target action， low side effects， and good therapeutic efficacy， has demonstrated an important role in anticancer treatment. A series of studies have investigated the role of Chinese medicine in inhibiting EMT in lung cancer. Active ingredients of Chinese medicine， including flavonoids， glycosides， phenols， terpenoids， saccharides， and alkaloids， as well as Chinese medicine compound formulas， have shown significant regulatory effects on EMT. Their mechanisms mainly involve multiple pathways， targets， and links， including signaling pathways， exosomes， microRNAs （miRNAs）， and the tumor-associated immune microenvironment. This article summarizes the mechanisms by which EMT promotes malignant tumor progression and reviews the current research on how Chinese medicine active ingredients， monomers， and compound formulas inhibit EMT and suppress lung cancer cell migration and invasion. This study is expected to provide comprehensive theoretical information for basic and translational research on lung cancer.

ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor （M1AChR） to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease （AD） model rats through the adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group， a model group， a Shenghui Tang group （9.3 g·kg^-1）， an exercise group， an exercise + Shenghui Tang group （9.3 g·kg^-1）， and a rapamycin group （1.5 mg·kg^-1）. Except for the blank group， the rat model of AD was constructed by injecting amyloid beta （Aβ_1-42） into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks， while the Shenghui Tang group received intragastric administration for 4 weeks， and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention， the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry （IHC）. The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. The expression of Beclin1 and microtubule-associated protein light chain 3β （LC3β） was detected by immunofluorescence （IF）. The protein expression of M1AChR， AMPK， p-AMPK， mTOR， Beclin1， LC3β， and chelate 1 （SQSTM1/p62） in hippocampus was detected by Western blot. ResultsCompared with the blank group， the model group exhibited significantly increased platform escape latency on the fifth day （P<0.01） and significantly decreased activity distance in the target quadrant and times of crossing the platform （P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed obviously decreased （P<0.05）. The arrangement of nerve cells in hippocampus CA1 region was dispersed， and the numbers of Nissl bodies and M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was significantly increased （P<0.01）. The typical autophagic lysosomal structure decreased. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly decreased （P<0.01）， and the protein expression of p62 was significantly increased （P<0.01）. Compared with the model group， the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly increased （P<0.01）. The number of Nissl bodies significantly increased （P<0.01）. The number of M1AChR positive cells in hippocampus was significantly increased （P<0.01）. The expression of TUNEL positive cells was significantly decreased （P<0.01）. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly increased （P<0.01）， while the protein expression of p62 was significantly decreased （P<0.01）. Compared with the exercise + Shenghui Tang group， the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day （P<0.01） and obviously decreased activity distance in the target quadrant and times of crossing the platform （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly decreased （P<0.01）. The number of Nissl bodies and the number of M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was obviously increased （P<0.05）. Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group （P<0.05， P<0.01）， while the protein expression of p62 was significantly increased （P<0.01）. In the exercise group， the protein expression of M1AChR， p-AMPK/AMPK， Beclin1， and LC3Ⅱ/Ⅰ was obviously decreased （P<0.05， P<0.01）， while the protein expression of p-mTOR/mTOR and p62 was significantly increased （P<0.01）. ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats， induce autophagy through the AMPK/mTOR signaling pathway， and improve the learning and memory ability of AD rats.

ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture （JDJM） in treating synovial lesions in knee osteoarthritis （KOA）. MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group （n=8） and a model group （n=35）. The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage， with a modeling period of 6 weeks， resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group， celecoxib group， JDJM group and JDJM+740Y-P group， each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg^-1， while the JDJM was administered a single dose of 6.8 mL·kg^-1 （4.515 2 g·kg^-1） of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway activator + JDJM group received 4.515 2 g·kg^-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg^-1 740Y-P. For a period of 6 weeks， the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period， the knee joint pain threshold and circumference were measured， and hematoxylin-eosin （HE） staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay （ELISA） measured the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-18） and tumor necrosis factor-α （TNF-α） in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， NOD-like receptor protein 3 （NLRP3）， cysteine-requiring aspartate protease-1 （Caspase-1） and gasdermin D （GSDMD） in the synovial tissues. Immunohistochemical （IHC） assay was performed to assess the protein expression of NLRP3， Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD. ResultsCompared to the blank group， the model group showed a significant increase in knee joint circumference and decrease in pain threshold， the synovial tissue pathology score was higher （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid significantly increased （P<0.01）. PI3K， Akt， mTOR phosphorylation as well as mRNA and protein expression increased （P<0.01）， while the mRNA and protein expression levels of NLRP3， Caspase-1 and GSDMD also significantly increased （P<0.01）. Compared to the model group， the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold， the synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid decreased （P<0.01）. The mRNA and protein expression of p-PI3K， p-Akt， p-mTOR， NLRP3， Caspase-1 and GSDMD were reduced （P<0.01）. Compared to the JDJM group， the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions， an increase in knee joint circumference， and a decrease in pain threshold. The synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid were higher （P<0.01）. The mRNA and protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD increased （P<0.01）. ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues， inhibiting pyroptosis， reducing inflammatory factor release， and protecting bony structures.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

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.

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

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