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1.
Langenbecks Arch Surg ; 409(1): 168, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38819706

RESUMO

PURPOSE: To evaluate the safety and efficacy of two-step vascular exclusion and in situ hypothermic portal perfusion in patients with end-stage hepatic hydatidosis. METHODS: This study involved patients with advanced hepatic hydatid disease undergoing surgical treatment between 2022 and 2023, which included resection and reconstruction of the hepatic veins, inferior vena cava (IVC), and portal vein (PV). We described the technical details of liver resection and vascular reconstruction, as well as the use of two-step vascular exclusion and in situ hypothermic portal perfusion techniques during the vascular reconstruction process. RESULT: We included 7 patients with advanced hepatic hydatid disease who underwent surgical resection using two-step vascular exclusion and in situ hypothermic portal perfusion. The mean duration of surgery was 12.5 h (range, 7.5-15.0 h). The average hepatic ischemia time was 45 min (range, 25-77 min), while the occlusion time of the IVC was 87 min (range, 72-105 min). The total blood loss was 1000 milliliters (range, 500-1250 milliliters). Postoperatively, patients exhibited good recovery of liver and renal function. The mean ICU stay was 2 days (range, 1-3 days), and the mean postoperative hospital stay was 13 days (range, 9-16 days), with no Grade III or above complications observed during a mean follow-up period of 15 months (range, 9-24 months), CONCLUSION: two-step vascular exclusion and in situ hypothermic portal perfusion for surgical resection of end-stage hepatic hydatid disease is safe and effective. This significantly reduces the anhepatic time.


Assuntos
Equinococose Hepática , Hepatectomia , Veia Porta , Veia Cava Inferior , Humanos , Equinococose Hepática/cirurgia , Equinococose Hepática/diagnóstico por imagem , Masculino , Feminino , Hepatectomia/métodos , Adulto , Pessoa de Meia-Idade , Veia Porta/cirurgia , Veia Cava Inferior/cirurgia , Hipotermia Induzida , Resultado do Tratamento , Perfusão/métodos , Estudos Retrospectivos , Veias Hepáticas/cirurgia , Idoso
3.
Blood Adv ; 8(7): 1651-1666, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38315834

RESUMO

ABSTRACT: Stress erythropoiesis can be influenced by multiple mediators through both intrinsic and extrinsic mechanisms in early erythroid precursors. Single-cell RNA sequencing was conducted on spleen tissue isolated from mice subjected to phenylhydrazine and serial bleeding to explore novel molecular mechanisms of stress erythropoiesis. Our results showed prominent emergence of early erythroblast populations under both modes of anemic stress. Analysis of gene expression revealed distinct phases during the development of emerging erythroid cells. Interestingly, we observed the presence of a "hiatus" subpopulation characterized by relatively low level of transcriptional activities that transitions between early stages of emerging erythroid cells, with moderate protein synthesis activities. Moreover, single-cell analysis conducted on macrophage populations revealed distinct transcriptional programs in Vcam1+ macrophages under stress. Notably, a novel marker, CD81, was identified for labeling central macrophages in erythroblastic islands (EBIs), which is functionally required for EBIs to combat anemic stress. These findings offer fresh insights into the intrinsic and extrinsic pathways of early erythroblasts' response to stress, potentially informing the development of innovative therapeutic approaches for addressing anemic-related conditions.


Assuntos
Anemia , Baço , Camundongos , Animais , Baço/metabolismo , Eritroblastos/metabolismo , Anemia/etiologia , Anemia/metabolismo , Eritropoese/fisiologia , Macrófagos/metabolismo
5.
Cancer Med ; 12(17): 18306-18316, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37609808

RESUMO

OBJECTIVE: This study aims to develop a risk prediction model for chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving highly emetogenic chemotherapy (HEC) and identify the variables that have the most significant impact on prediction. METHODS: Data from Tianjin Medical University General Hospital were collected and subjected to stepwise data preprocessing. Deep learning algorithms, including deep forest, and typical machine learning algorithms such as support vector machine (SVM), categorical boosting (CatBoost), random forest, decision tree, and neural network were used to develop the prediction model. After training the model and conducting hyperparameter optimization (HPO) through cross-validation in the training set, the performance was evaluated using the test set. Shapley additive explanations (SHAP), partial dependence plot (PDP), and Local Interpretable Model-Agnostic Explanations (LIME) techniques were employed to explain the optimal model. Model performance was assessed using AUC, F1 score, accuracy, specificity, sensitivity, and Brier score. RESULTS: The deep forest model exhibited good discrimination, outperforming typical machine learning models, with an AUC of 0.850 (95%CI, 0.780-0.919), an F1 score of 0.757, an accuracy of 0.852, a specificity of 0.863, a sensitivity of 0.784, and a Brier score of 0.082. The top five important features in the model were creatinine clearance (Ccr), age, gender, anticipatory nausea and vomiting, and antiemetic regimen. Among these, Ccr had the most significant predictive value. The risk of CINV decreased with increased Ccr and age, while it was higher in the presence of anticipatory nausea and vomiting, female gender, and non-standard antiemetic regimen. CONCLUSION: The deep forest model demonstrated good discrimination in predicting the risk of CINV in cancer patients prescribed HEC. Kidney function, as represented by Ccr, played a crucial role in the model's prediction. The clinical application of this predictive tool can help assess individual risks and improve patient care by proactively optimizing the use of antiemetics in cancer patients receiving HEC.


Assuntos
Antieméticos , Antineoplásicos , Aprendizado Profundo , Neoplasias , Humanos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/diagnóstico , Náusea/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico
6.
Hum Cell ; 36(6): 2259-2269, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37603218

RESUMO

Peritoneal mesenchymal stromal cells (pMSCs) are isolated from peritoneal dialysis (PD) effluent, and treatment with the pMSCs reduces peritoneal membrane injury in rat model of PD. This study was designed to verify the identity of the pMSCs. pMSCs were grown in plastic dishes for 4-7 passages, and their cell surface phenotype was examined by staining with a panel of 242 antibodies. The positive stain of each target protein was determined by an increase in fluorescence intensity as compared with isotype controls in flow cytometrical analysis. Here, we showed that pMSCs predominantly expressed CD9, CD26, CD29, CD42a, CD44, CD46, CD47, CD49b, CD49c, CD49e, CD54, CD55, CD57, CD59, CD63, CD71, CD73, CD81, CD90, CD98, CD147, CD151, CD200, CD201, ß2-micoglobulin, epithelial growth factor receptor, human leukocyte antigen (HLA) class 1, and, to a lesser extent, CD31, CD45RO, CD49a, CD49f, CD50, CD58, CD61, CD105, CD164, and CD166. These cells lacked expression of most hematopoietic markers such as CD11b, CD14, CD19, CD34, CD40, CD80, CD79, CD86, and HLA-DR. There was 38.55% difference in the expression of 83 surface proteins between bone marrow (BM)-derived MSCs and pMSCs, and 14.1% in the expression of 242 proteins between adipose tissue (AT)-derived MSCs and pMSCs. The BM-MSCs but not both AT-MSCs and pMSCs express cytokine receptors (IFNγR, TNFI/IIR, IL-1R, IL-4R, IL-6R, and IL-7R). In conclusion, pMSCs exhibited a typical cell surface phenotype of MSCs, which was not the same as on BM-MSCs or AT-MSCs, suggesting that the pMSCs may represent a different MSC lineage from peritoneal cavity.

7.
Foods ; 12(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37444250

RESUMO

Camellia taliensis (W. W. Smith) Melchior, belonging to the genus Camellia sect. Thea., is mainly distributed from northern Myanmar to western and southwestern Yunnan province of China, and its leaves have been used to make various teas by the locals of its growing regions. The chemical constituents of C. taliensis are significantly related to those of cultivated tea plants, C. sinensis and C. sinensis var. assamica. The HPLC-ESI-MS analysis of black tea prepared from the leaves of C. taliensis showed a rich existence of polyphenols. Further comprehensive chemical study led to the separation and recognition of 32 compounds (1-32), including one new hydrolyzable tannin, 1-O-galloyl-4,6-tetrahydroxydibenzofurandicarboxyl-ß-D-glucopyranose (1), and one new natural product (24). The known compounds referred to seven hydrolyzable tannins (2-8), 10 flavonols and glycosides (9-18), and 14 simple phenolics (19-32). Their structures were elucidated by comprehensive spectroscopic analyses. Among them, 20 compounds (2, 3, 6, 7, 8, 15, 17, 18, 20-22, 24-32) were isolated from black tea for the first time. Most isolates displayed obvious antioxidant activities on DPPH and ABTS+ assays, and the hydrolyzable tannins 1, 3-5, 7, and 8 exhibited stronger inhibitory activities on α-glycosidase than quercetin and acarbose (IC50 = 5.75 and 223.30 µM, respectively), with IC50 values ranging from 0.67 to 2.01 µM.

8.
J Dig Dis ; 24(2): 70-84, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37220999

RESUMO

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.


Assuntos
Gastroscopia , Humanos , Gastroscopia/métodos , Magnetismo
9.
Pharmacol Res ; 192: 106789, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149115

RESUMO

Oral multitarget tyrosine kinase inhibitors (TKIs), such as sorafenib, which suppress tumor cell proliferation and tumor angiogenesis, have been approved to treat patients with hepatocellular carcinoma (HCC). Of note, only approximately 30% of patients can benefit from TKIs, and this population usually acquires drug resistance within 6 months. In this study, we intended to explore the mechanism associated with regulating the sensitivity of HCC to TKIs. We revealed that integrin subunit ß 5 (ITGB5) is abnormally expressed in HCC and contributes to decreased the sensitivity of HCC to sorafenib. Mechanistically, unbiased mass spectrometry analysis using ITGB5 antibodies revealed that ITGB5 interacts with EPS15 to prevent the degradation of EGFR in HCC cells, which activates AKT-mTOR signaling and the MAPK pathway to reduce the sensitivity of HCC cells to sorafenib. In addition, mass spectrometry analysis showed that CSNK1A1 binds to ITGB5 in HCC cells. Further study indicated that ITGB5 increased the protein level of CSNK1A1 through the EGFR-AKT-mTOR pathway in HCC. Upregulated CSNK1A1 phosphorylates ITGB5 to enhance the interaction between ITGB5 and EPS15 and activate EGFR in HCC cells. Thus, we identified a positive feedback loop between ITGB5-EPS15-EGFR-CSNK1A1 in HCC cells. This finding provides a theoretical basis for the future development of therapeutic strategies to improve the anti-HCC efficacy of sorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/metabolismo , Regulação para Cima , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células , Serina-Treonina Quinases TOR/metabolismo , Receptores ErbB , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
10.
RSC Adv ; 13(16): 11037-11043, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37033442

RESUMO

Panax notoginseng (PN) is a well-known traditional Chinese medicine, with dammarane-type triterpenoid saponins characterized as major component and active ingredients, together with amino acids, flavonoids, polysaccharides, and polyacetylenes. The roots of PN are susceptible to root rot disease, which causes a huge loss and changes in the chemical components of this precious resource. In this study, sub-fractions of rot PN root extracts were preliminarily found to have admirable cytotoxicity on two human cancer cells. Further bioassay-guided isolation discovered nine new non-triterpenoids, including two novel N-methylacetamido-1-oxotetrahydropyrimidine alkaloids (1, 2), five 2H-furanones or 2H-pyranones (3-7), and two polyacetylenic alcohols (8, 9). Their structures were illuminated by extensive spectroscopic data, calculated ECD, and X-ray diffraction analysis. Among them, 3-7 were considered to be transformed from panaxatriol through the intermediates (8, 9). The new alkaloids (1, 2) displayed noteworthy cytotoxicity against five human cancer cells with IC50 values ranging from 14 to 24 µM. In silico target prediction and molecular docking studies showed that 1 and 2 may interact with EGFR, and were verified by the experimental inhibitory effect on EGFR tyrosine kinase.

11.
BMC Med Genomics ; 16(1): 58, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949429

RESUMO

BACKGROUND: Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC. METHODS: First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan-Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model. RESULT: Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan-Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR. CONCLUSION: The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.


Assuntos
Apoptose , Neoplasias Colorretais , RNA Longo não Codificante , Humanos , Algoritmos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Prognóstico , RNA Longo não Codificante/genética , Cobre
12.
Eur J Med Res ; 28(1): 83, 2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36805825

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly males, and many kinds of minimally invasive procedures can be used for the treatment of BPH. However, various procedures have caused some controversies regarding clinical outcomes, so more studies are needed to validate these controversial topics. AIMS: This study aimed to explore differences of clinical efficacy, surgical features, and complications between transurethral resection of the prostate (TURP) and plasmakinetic enucleation of the prostate (PKEP) for BPH. METHODS: A total of eligible 850 cases of BPH underwent TURP (the TURP group, 320 cases) or PKEP (the PKEP group, 530 cases) in the urology department of our hospital from March 2015 to 2018 were involved in this study. Then, the baseline data, surgical characteristics, IPSS, QoL, PVR, Qmax, IIEF-5, and documented complications were compared between the two groups. RESULTS: The operative time, intraoperative irrigation volume, postoperative hemoglobin, decrease in hemoglobin, postoperative irrigation time and volume, catheterization time, and hospital stay of the PKEP group were significantly less than those of the TURP group (all P < 0.05). At 3 months, 1, 2, and 3 years after operation, no significant differences were observed in IPSS, QoL, PVR, but the results of Qmax and IIEF-5 in the PKEP group were significantly higher than those parameters in the TURP group (all P < 0.05). The incidences of massive blood loss, postoperative secondary bleeding, blood transfusion, capsular perforation, urinary tract irritation, bladder spasm, clot retention, urinary tract infection, transient incontinence, erectile dysfunction, and the incidences of II, III grade of Clavien-Dindo classification in the PKEP group were significantly lower than those of the TURP group (all P < 0.05). CONCLUSION: The clinical efficacy of PKEP is compared favorably with TURP during midterm follow-up. Given the merits such as less blood loss and hospital stay, lower complications, PKEP should be given a priority for BPH.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Idoso , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Resultado do Tratamento , Hemorragia Pós-Operatória
14.
Cell Death Dis ; 14(1): 47, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670097

RESUMO

For patients with advanced or metastatic Hepatocellular carcinoma (HCC) who are not suitable for surgical resection, systemic therapy has been considered to be the standard treatment. In recent years, a small subset of patients with unresectable HCC have been benefit from tyrosine kinase inhibitors (TKIs), and the overall survival time of these patients is significantly increased. However, all responders ultimately develop resistance to TKI treatment. The tripartite motif (TRIM) family member TRIM15 acts as an E3 ligase to mediate the polyubiquitination of substrates in cells. However, the biological role of TRIM15 in HCC is still an enigma. In our study, our results demonstrated that TRIM15 was abnormally upregulated in liver cancer cells after treated with TKIs and that this upregulation of TRIM15 contributed to TKI resistance in liver cancer cells. Then, we demonstrated that the upregulation of TRIM15 after TKI treatment was mediated by the AKT/FOXO1 axis. Moreover, we demonstrated that TRIM15 induced the nuclear translocation of LASP1 by mediating its K63-linked polyubiquitination, which modulated sensitivity to TKIs by increasing the phosphorylation of AKT and the expression of Snail in liver cancer cells. Collectively, we identified a novel AKT/FOXO1/TRIM15/LASP1 loop in cells, which provided potential candidates for overcoming TKI resistance in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas Proto-Oncogênicas c-akt , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Transporte , Linhagem Celular Tumoral , Proteína Forkhead Box O1/genética , Proteínas do Citoesqueleto , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas com Domínio LIM
15.
Adv Fiber Mater ; 5(2): 497-513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36530771

RESUMO

Hard-to-dissolve polymers provide next-generation alternatives for high-performance filter materials owing to their intrinsically high chemical stability, superior mechanical performance, and excellent high-temperature resistance. However, the mass production of hard-to-dissolve nanofibers still remains a critical challenge. A simple, scalable, and low-cost ionic solution blow-spinning method has herein been provided for the large-scale preparation of hard-to-dissolve Nomex polymeric nanofibers with an average diameter of nearly 100 nm. After rapidly dissolving Nomex microfibers in the lithium chloride/dimethylacetamide (LiCl/DMAc) solution system, the conductive solution can be stably and conductivity-independently processed into nanofibers. The method optimizes electrospinning and avoids spinnability degradation and potential safety hazards caused by high electrical conductivity. Owing to nanofibrous structure and high dipole moment, Nomex nanofibrous filters show a stable high filtration efficiency of 99.92% for PM0.3 with a low areal density of 4.6 g m-2, as well as a low-pressure drop of 189.47 Pa. Moreover, the flame-retardant filter can work at 250 °C and 280 °C for a long and short time without shrinking or burning, respectively, exhibiting a high filtration efficiency of 99.50% for PM0.3-10.0. The outstanding properties and low cost enable the efficient capture of PM from various high-temperature exhausts, making Nomex nanofibrous membrane an even more ideal industrial-grade air filter than polypropylene, polytetrafluoroethylene, polyimide, and ceramic nanofibrous filters. Graphical abstract: Hard-to-dissolve nanofibers provide alternatives for high-efficiency and low-resistant air filtration but are limited by the universality and economics of fabrication methods. A scalable and efficient ionic solution blow-spinning strategy has herein been proposed in preparing hard-to-dissolve nanofibrous filters. Supplementary Information: The online version contains supplementary material available at 10.1007/s42765-022-00231-x.

19.
J Int Med Res ; 50(12): 3000605221142401, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36539966

RESUMO

Pancreatic follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with unclear pathological characteristics. In this study, we report one case of pancreatic FDCS and review published cases to summarize the characteristics and treatment of pancreatic FDCS. A man in his early 30 s was admitted for jaundice, abdominal fullness, and weight loss for 15 days. Computed tomography revealed a large capsule solid mass in the pancreatic head together with a dilated bile duct and enlarged retroperitoneal lymph nodes. Serum biochemistry revealed high total bilirubin levels (313.9 µmol/L) and normal tumor marker levels. Pancreatoduodenectomy was performed, but no chemotherapy was administrated at the patient's behest. The pathologic diagnosis was pancreatic FDCS infiltrating the duodenal seromuscular layer and common bile duct. The patient presented with liver metastasis 3 months after surgery and died 8 months after surgery from multiorgan failure. Pancreatic FDCS is a rare disease with high invasiveness. Our previous case exhibited paraneoplastic syndrome together with this disease, and further investigation is needed to confirm whether paraneoplastic syndrome is a typical syndrome of pancreatic FDCS.


Assuntos
Sarcoma de Células Dendríticas Foliculares , Neoplasias Hepáticas , Síndromes Paraneoplásicas , Masculino , Humanos , Sarcoma de Células Dendríticas Foliculares/diagnóstico por imagem , Sarcoma de Células Dendríticas Foliculares/cirurgia , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pâncreas/patologia , Pancreaticoduodenectomia , Neoplasias Hepáticas/cirurgia , Síndromes Paraneoplásicas/cirurgia
20.
Cureus ; 14(9): e29698, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36321032

RESUMO

Kratom is a plant product native to Southeast Asia that is surging in popularity in the United States as consumers look for natural remedies for ailments like chronic pain, anxiety, and even opioid addiction. Kratom's risks are largely unknown, and the market is poorly regulated. Americans typically get advice from online forums and purchase powder formulations from tobacco shops or obscure websites. These risks are highlighted in this case of a 38-year-old woman with a history of major depressive disorder and opioid use disorder who switched from Suboxone to kratom and became addicted, eventually consuming large quantities per day. Amplified by other stressors, she reached a breaking point and overdosed on her regular medications for depression. At the psychiatric hospital, she exhibited classic kratom withdrawal symptoms, including vague abdominal pain and restlessness. After eight days of treatment, her symptoms eventually abated, and she was discharged on Suboxone.

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