Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital

BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.

Lymphatic plastic bronchitis and primary chylothorax: A study based on computed tomography lymphangiography

BACKGROUND This study presents an evaluation of the computed tomography lymphangio-graphy(CTL)features of lymphatic plastic bronchitis(PB)and primary chylotho-rax to improve the diagnostic accuracy for these two diseases.AIM To improve the diagnosis of lymphatic PB or primary chylothorax,a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed.METHODS The clinical and CTL data of 71 patients(20 with lymphatic PB,41 with primary chylothorax,and 10 with lymphatic PB with primary chylothorax)were collected retrospectively.CTL was performed in all patients.The clinical manifestations,CTL findings,and conventional chest CT findings of the three groups of patients were compared.The chi-square test or Fisher's exact test was used to compare the differences among the three groups.A difference was considered to be statistically significant when P<0.05.RESULTS(1)The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows:Thoracic duct outlet in 14(70.0%),33(80.5%)and 8(80.0%)patients;peritracheal region in 18(90.0%),15(36.6%)and 8(80.0%)patients;pleura in 6(30.0%),33(80.5%)and 9(90.0%)patients;pericardium in 6(30.0%),6(14.6%)and 4(40.0%)patients;and hilum in 16(80.0%),11(26.8%)and 7(70.0%)patients;and(2)the abnormalities on conven-tional chest CT in the three groups were as follows:Ground-glass opacity in 19(95.0%),18(43.9%)and 8(80.0%)patients;atelectasis in 4(20.0%),26(63.4%)and 7(70.0%)patients;interlobular septal thickening in 12(60.0%),11(26.8%)and 3(30.0%)patients;bronchovascular bundle thickening in 14(70.0%),6(14.6%)and 4(40.0%)patients;localized mediastinal changes in 14(70.0%),14(34.1%),and 7(70.0%)patients;diffuse mediastinal changes in 6(30.0%),5(12.2%),and 3(30.0%)patients;cystic lesions in the axilla in 2(10.0%),6(14.6%),and 2(20.0%)patients;and cystic lesions in the chest wall in 0(0%),2(4.9%),and 2(4.9%)patients.CONCLUSION CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax.This method is an excellent tool for diagnosing these two diseases.

Role of lipids in the control of autophagy and primary cilium signaling in neurons

The brain is,after the adipose tissue,the organ with the greatest amount of lipids and diversity in their composition in the human body.In neurons,lipids are involved in signaling pathways controlling autophagy,a lysosome-dependent catabolic process essential for the maintenance of neuronal homeostasis and the function of the primary cilium,a cellular antenna that acts as a communication hub that transfers extracellular signals into intracellular responses required for neurogenesis and brain development.A crosstalk between primary cilia and autophagy has been established;however,its role in the control of neuronal activity and homeostasis is barely known.In this review,we briefly discuss the current knowledge regarding the role of autophagy and the primary cilium in neurons.Then we review the recent literature about specific lipid subclasses in the regulation of autophagy,in the control of primary cilium structure and its dependent cellular signaling in physiological and pathological conditions,specifically focusing on neurons,an area of research that could have major implications in neurodevelopment,energy homeostasis,and neurodegeneration.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Spatiotemporal changes of gross primary productivity and its response to drought in the Mongolian Plateau under climate change

Gross primary productivity(GPP)of vegetation is an important constituent of the terrestrial carbon sinks and is significantly influenced by drought.Understanding the impact of droughts on different types of vegetation GPP provides insight into the spatiotemporal variation of terrestrial carbon sinks,aiding efforts to mitigate the detrimental effects of climate change.In this study,we utilized the precipitation and temperature data from the Climatic Research Unit,the standardized precipitation evapotranspiration index(SPEI),the standardized precipitation index(SPI),and the simulated vegetation GPP using the eddy covariance-light use efficiency(EC-LUE)model to analyze the spatiotemporal change of GPP and its response to different drought indices in the Mongolian Plateau during 1982-2018.The main findings indicated that vegetation GPP decreased in 50.53% of the plateau,mainly in its northern and northeastern parts,while it increased in the remaining 49.47%area.Specifically,meadow steppe(78.92%)and deciduous forest(79.46%)witnessed a significant decrease in vegetation GPP,while alpine steppe(75.08%),cropland(76.27%),and sandy vegetation(87.88%)recovered well.Warming aridification areas accounted for 71.39% of the affected areas,while 28.53% of the areas underwent severe aridification,mainly located in the south and central regions.Notably,the warming aridification areas of desert steppe(92.68%)and sandy vegetation(90.24%)were significant.Climate warming was found to amplify the sensitivity of coniferous forest,deciduous forest,meadow steppe,and alpine steppe GPP to drought.Additionally,the drought sensitivity of vegetation GPP in the Mongolian Plateau gradually decreased as altitude increased.The cumulative effect of drought on vegetation GPP persisted for 3.00-8.00 months.The findings of this study will improve the understanding of how drought influences vegetation in arid and semi-arid areas.

Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.

Significance of Primary Treatment Selection in the Efficiency of Wastewater Treatment in Constructed Wetlands (CWs)

This research explores strategies to enhance the efficiency of secondary treatment in Vertical Flow Constructed Wetlands (CW) in Montenegro. The focus is on selecting appropriate primary treatment methods alongside three distinct substrate types to improve wastewater treatment efficacy. The study examines the combination of two primary treatments with different substrate types in constructed wetlands (CW1, CW2, and CW3). The primary treatments include the existing wastewater treatment plant (WWTP) in Podgorica, involving coarse material removal through screens, inert material separation in aerated sand traps, and sediment and suspended matter removal in primary sedimentation tanks. The Extreme Separator (ExSep) was employed to evaluate its efficacy as a primary treatment method. The research demonstrates that the efficiency of CW can be significantly enhanced by selecting suitable primary treatment methods and substrates in Podgorica’s conditions. The most promising results were achieved by combining ExSep as a primary treatment with secondary treatment in CW-3. The removal efficiencies after CW3 for COD, BOD, and TSS exceeded 89%, 93%, and 91%, respectively. The outcomes underscore the significance of primary treatment in mitigating pollutant loads before discharge into the constructed wetlands, emphasizing potential areas for further optimization in wastewater treatment practices to enhance environmental sustainability and water quality management.

One Case of Primary Thrombocythemia with Concealed Hypokalemia Complicated by Acute Myocardial Infarction

Medical history summary: Male, 47 years old, was admitted to the hospital due to “dizziness accompanied by chest tightness and pain for more than 8 days”. One week ago, the patient experienced chest tightness, chest pain accompanied by profuse sweating for 3 hours and underwent emergency percutaneous coronary intervention (PCI) at a local hospital. The procedure revealed left main stem occlusion with subsequent left main stem to left anterior descending artery percutaneous transluminal coronary angioplasty (PTCA). After the procedure, the patient experienced hemodynamic instability, recurrent ventricular fibrillation, and critical condition, thus transferred to our hospital for further treatment. Symptoms and signs: The patient is in a comatose state, unresponsive to stimuli, with bilateral dilated pupils measuring 2.0 mm, exhibiting reduced sensitivity to light reflex, and recurrent fever. Coarse breath sounds can be heard in both lungs, with audible moist rales. Irregular breathing pattern is observed, and heart sounds vary in intensity. No pathological murmurs are auscultated in any valve auscultation area. Diagnostic methods: Coronary angiography results at the local hospital showed complete occlusion of the left main stem, and left main stem to left anterior descending artery percutaneous transluminal coronary angioplasty (PTCA) was performed. However, the distal guidewire did not pass through. After admission, blood tests showed a Troponin T level of 1.44 ng/ml and a Myoglobin level of 312 ng/ml. The platelet count was 1390 × 109/L. Von Willebrand factor (vWF) activity was measured at 201.9%. Bone marrow aspiration biopsy showed active bone marrow proliferation and platelet clustering. The peripheral blood smear also showed platelet clustering. JAK-2 gene testing was positive, confirming the diagnosis of primary thrombocytosis. Treatment methods: The patient is assisted with mechanical ventilation and intra-aortic balloon counterpulsation to improve coronary blood flow. Electrolyte levels are closely monitored, especially maintaining plasma potassium levels between 4.0 and 4.5 mmol/l. Hydroxyurea 500 mg is administered for platelet reduction. Anticoagulants and antiplatelet agents are used rationally to prevent further infarction or bleeding. Antiarrhythmic, lipid-lowering, gastroprotective, hepatoprotective, and heart failure treatment are also provided. Clinical outcome: The family members chose to withdraw treatment and signed for discharge due to a combination of reasons, including economic constraints and uncertainty about the prognosis due to the long disease course. Acute myocardial infarction has gradually become one of the leading causes of death in our country. As a “green channel” disease, corresponding diagnostic and treatment protocols have been established in China, and significant progress has been made in emergency care. There are strict regulations for the time taken from the catheterization lab to the cardiac intensive care unit, and standardized treatments are provided to patients once they enter the intensive care unit. Research results show that the incidence of acute myocardial infarction in patients with primary thrombocythemia within 10 years is 9.4%. This type of disease is rare and difficult to cure, posing significant challenges to medical and nursing professionals. In order to benefit future patients, we have documented individual cases of treatment and nursing care for these patients. The research results show that these patients exhibit resistance to traditional oral anticoagulant drugs and require alternative anticoagulants. Additionally, there are significant differences in serum and plasma potassium levels among patients. Therefore, when making clinical diagnoses, it is necessary to carefully distinguish between the two. Particularly, nursing personnel should possess dialectical thinking when supplementing potassium levels in patients in order to reduce the incidence of malignant arrhythmias and mortality rates.

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Primary Hyperoxaluria Type 1 in Adulthood: Case Series

Introduction: Primary hyperoxaluria type 1 (HP1) is a rare lithiasis with systemic involvement, due to the accumulation of calcium oxalate crystals. In the absence of therapeutic management, it progresses to end-stage chronic renal failure. The aim of this study is to describe and analyse the observations of our patients with HP1. Patients and methods: This is a retrospective study carried out between 2014 and 2023 in the Nephrology-Dialysis Transplant Department of the Ibn Sina University Hospital in Rabat. The clinical, paraclinical and evolutionary elements were taken from the patients’ medical records. Results: We collected 11 cases, with a mean age of 27 ± 8.5 years and a M/F sex ratio of 1.7. The diagnosis of HP1 was made on the basis of genetic analysis in 8 patients, morphological and spectro-photometric analysis of the calculus in one patient, biopsy of the graft in one patient and crystalluria and a family history of PH1 in one patient. Two patients died, and 8 patients were on chronic haemdialysis with systemic damage. Only one patient maintained a stable GFR at 60 ml/min. Conclusion: Early diagnosis combined with conservative treatment is the only way to limit the rapid progression of this disease. This requires awareness and collaboration between nephrologists, urologists and biologists within a specialised team.

Exploration of the complex origins of primary constipation

Constipation is a common gastrointestinal disorder characterized by infrequentbowel movements and difficulty in passing stools.It can significantly affect anindividual's quality of life and overall well-being.Understanding the causes ofconstipation is important for its effective management and treatment.In thispaper,we have reviewed the primary causes of constipation or functional constipation.Primary constipation is a bowel disorder associated with colonic oranorectal sensorimotor or neuromuscular dysfunction.As per the literature,it ismultifactorial and involves factors such as decreased interstitial cells of Cajal,altered colonic motility,enteric nervous system dysfunction,intestinal flora disturbances,and psychological influences.Clinical symptoms include difficulty indefecation,decreased frequency of defecation,or a feeling of incomplete evacuation.A comprehensive evaluation and management of constipation require aninterdisciplinary approach incorporating dietary modifications,lifestyle changes,pharmacotherapy,and psychological interventions.Further research is imperativeto explain the intricate mechanisms underlying constipation and develop targetedtherapies for improved patient outcomes.