Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Update on the current management of persistent and recurrent primary hyperparathyroidism after parathyroidectomy

Primary hyperparathyroidism(pHPT)is the third most common endocrine disease.The surgical procedure aims for permanent cure,but recurrence has been reported in 4%-10%of pHPT patients.Preoperative localization imaging is highly valuable.It includes ultrasound,computed tomography(CT),single-photonemission CT,sestamibi scintigraphy and magnetic resonance imaging.The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months.Ongoing hypercalcemia during this period is defined as persistence,and recurrence is defined as hypercalcemia after six months of normocalcemia.Vitamin D is a crucial factor for a good outcome.Intraoperative parathyroid hormone(PTH)monitoring can safely predict the outcomes and should be suggested.PTH≤40 pg/mL or the traditional decrease≥50%from baseline minimizes the likelihood of persistence.Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology.Risk factors for recurrence are cardiac history,obesity,endoscopic approach and low-volume center(at least 31 cases/year).Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/recurrence.A 6-mo calcium>9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up.18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation.With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement,the recurrence rate has dropped to 2.5%-5%.Sixmonth serum calcium≥9.8 mg/dL and parathyroid hormone≥80 pg/mL indicate a risk of recurrence.Negative sestamibi scintigraphy,diabetes and elevated osteocalcin levels are predictors of multiglandular disease,which brings an increased risk of persistence and recurrence.Bilateral neck exploration was considered the gold-standard diagnostic method.Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques.Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence.Long-term follow-up,even up to 10 years,is necessary.

The role and mechanism of fatty acids in gallstones

BACKGROUND: Cholelithiasis is a common entity in China, but its etiology and pathogenesis have not been fully elucidated. Pigment stones of the intrahepatic and extrahepatic bile duct still form a high proportion in China, while they are rare in Europeans. To date, reports on fatty acids in stones remain few. We analyzed the quantity of fatty acids in different stones from Chinese and Japanese cases and discussed the role and mechanism of fatty acids in the formation of pigment stones. METHODS: Clinical data from 18 Chinese and 37 Japanese patients with different types of stones were analyzed using the procedure for extracting fatty acids from gallstones and high performance liquid chromatography. RESULTS: The total fatty acid and free fatty acid contents of pigment stones were markedly higher than those in black or cholesterol stones. The ratio of free saturated to free unsaturated fatty acids was highest in intrahepatic and less in extrahepatic pigment stones, which were significantly different from the other two kinds of stones. CONCLUSIONS: This indicates that phospholipase participates in the course of pigment stone formation. The action of phospholipase A1 is more important than phospholipase A2.

Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma

AIM： A few studies have applied genomic-wide gene expression analysis in inflamed colon tissue sample in ulcerative colitis （UC）. We reported the first study of non-inflamed mucosal gene expression in UC and explored its clinical implication. METHODS： Non-inflamed mucosa was obtained from 6 UC patients who received total colectomy. The gene expression of UC in noninflamed mucosa was monitored with a microarray. For a selected gene, RT-PCR was performed to verify array results and to further examine expression pattern in inflamed mucosa of UC, colorectal cancer tissue and normal mucosa using additional matched pairs. RESULTS： Two genes showing 2.5-fold decreased expression with significance set at in UC samples were borneo box a4 （HOXa4） and mads box transcription enhancer factor 2, polypeptide B （MEF2b）. RT-PCR showed that MEF2b expression in non-inflamed mucosa was significantly downregulated, whereas the expression of MEF2b increased in accordance with the severity of mucosal inflammation. HOXa4 expression both in inflamed and non-inflamed mucosa in UC was consistently downregulated, and the downregulation of HOXa4 was also found in colorectal carcinoma. CONCLUSION： It is suggested that the MEF2b expression in UC which increase in accordance with inflammation may be induced by the inflammatory mediator. In contrast the downregulation of HOXa4 may be partly involved in the pathogenesis of disease including UC and UC-related carcinogenesis.

Secondary pouchitis in a post-operative patient with ulcerative colitis,successfully treated by salvage surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery. A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouchanal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnantrectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were constructed.The postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.

PULMONARY THROMBOEMBOLISM FOLLOWING THORACOTOMY FOR LUNG CANCER

Objective： To investigate the clinical features of pulmonary thromboembolism in patients with primary lung cancer in relation to thoracotomy, and to shed light on prevention, diagnosis and treatment of this fatal disease after lung resection. Methods： A total of 1245 cases with primary lung cancer received thoracotomy in the past 13 years were retrospectively reviewed. Clinical data of a total of 14 patients （1.1%） suffering from pulmonary thromboembolism and requiring cardiao-pulmonary resuscitation were collected and analyzed. Results： The diagnosis was established primarily by clinical findings in 9 cases （64.3%）, including further confirmation of one case during operation, by pulmonary ventilation-perfusion scan in 2, by spiral CT angiography in I, by pulmonary angiography in 1, and by autopsy in I case. Even using prompt resuscitation, 8 patients （57.1%） died within 48 h （mean 4 h） after the onset of the symptoms. Six cases eventually recovered. Of the 6 salvaged patients, they all received anticoagulation therapy with heparin intravenously and warfarin orally, including 3 cases of additional thrombolytic therapy with urokinase. Two cases with massive pulmonary emboli received emergency surgery, including one pulmonary embolectomy, and one bilobectomy after right upper Iobectomy, with satisfactory results. Conclusion： Massive pulmonary embolism is an infrequent but fatal early postoperative complication after lung resection. The diagnosis should be based mainly on clinical findings in order to initiate the appropriate therapy immediately. The direct diagnostic techniques including radionuclide pulmonary scan, spiral CT angiography, and pulmonary angiograpby could be based on a careful evaluation of the expected benefits and risks of the various available treatments.