In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

Objective To analyze the expression of microRNA(miR)-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis(TBM)and their predictive value for disease severity and prognosis.Methods A total of 187 patients with tuberculous meningitis who visited Qingdao Chest Hospital from January 2018 to December 2022 were regarded and separated into stage Ⅰ(n=62),stage Ⅱ(n=76)and stage Ⅲ(n=49)according to the severity of the condition.There were 131 cases in the good prognosis group and 56 cases in the poor prognosis group according to the prognosis.The qRT-PCR method was applied to detect the expression levels of miR-200a and miR-4652-3p in cerebrospinal fluid.Spearman method was used to analyze correlation among miR-200a,miR-4652-3p and clinical data.ROC curve was applied to analyze the predictive value of cerebrospinal fluid miR-200a and miR-4652-3p levels in evaluating the severity and prognosis of tuberculosis meningitis patients.Multivariate logistic regression was applied to analyze the influencing factors of poor prognosis in patients.Results The expression levels of miR-200a(1.05±0.14,0.91±0.14,0.76±0.13)and miR-4652-3p(0.92±0.11,0.78±0.11,0.65±0.10)in the cerebrospinal fluid of patients with stage Ⅰ,Ⅱ,and Ⅲ tuberculous meningitis were decreased sequentially,and the differences were significant(F=61.079,87.203,all P＜0.05).The expression levels of miR-200a(0.95±0.14)and miR-4652-3p(0.82±0.11)in cerebrospinal fluid of patients with good prognosis tuberculous meningitis were higher than those of patients with poor rognosis(0.84±0.13,0.73±0.10),and the differences were statistically significant(t=5.025,5.262,all P＜0.05),while the levels of cerebrospinal fluid adenosine deaminase,TNF-α,IL-23,LTB4,CRP and mRS scores in patients with good prognosis were lower than those in patients with poor prognosis(t=5.649,7.721,11.150,9.455,11.314,14.407,all P＜0.05).There was a positive correlation between the levels of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis(r=0.405,P＜0.001).The levels of miR-200a and miR-4652-3p in cerebrospinal fluid were negatively correlated with LTB4,TNF-ot,CRP,mRS scores,IL-23 and adenosine deaminase(r=-0.472,-0.466,-0.461,-0.435,-0.422,-0.419;-0.459,-0.531,-0.471,-0.417,-0.513,-0.408,all P＜0.05).The AUC(95％CI)of miR-200a and miR-4652-3p to assess disease severity were 0.881(0.825～0.923)and 0.878(0.822～0.921),respectively.The AUC(95％CI)of both combination in assessing the severity of patients was 0.945(0.902～0.973),which was higher than the single detection,and the differences were significant(Z=3.008,2.960,all P=0.003).The AUC(95％CI)of poor prognosis patients evaluated by cerebrospinal fluid miR-200a and miR-4652-3p levels were 0.749(0.681～0.809)and 0.756(0.688～0.816),and the AUC of poor prognosis patients evaluated by both combination was 0.839(0.778～0.889),which was higher than that measured separately,and the differences were significant(Z=2.994,2.697,P=0.003,0.007).Adenosine deaminase[OR(95％CI):1.106(1.033～1.185)],miR-200a[OR(95％CI):0.529(0.369～0.744)],miR-4652-3p[OR(95％CI):0.471(0.310～0.715)],C-reactive protein[OR(95％CI):4.423(1.459～13.412)],TNF-α[OR(95％CI):1.196(1.061～1.348)],IL-23[OR(95％CI):4.809(1.086～3.013)],and LTB4[OR(95％CI):1.327(1.064～1.655)]were influencing factors for poor prognosis in patients with tuberculous meningitis(all P＜0.05).Conclusion The expressions of miR-200a and miR-4652-3p in cerebrospinal fluid of patients with tuberculous meningitis were down-regulated,and they were closely related to the severity and prognosis of the disease.The combination of the miR-200a and miR-4652-3p could better predict the severity and prognosis of tuberculous meningitis,which may have a certain clinical value.

OBJECTIVES: To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells. METHODS: CCK-8 assay was used to determine the 48-h IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed. RESULTS: The IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA. CONCLUSIONS AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.
Animals ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/pathology* ; Mice, Nude ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Humans ; Female ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Drug Synergism ; MDA-MB-231 Cells

Objective To investigate the current demand for extended nursing services for newborns after discharge.Methods A survey was conducted on the demand for extended nursing services after discharge of newborns using the"Survey Form for Demand for Extended Nursing Services after Discharge of Newborns",and the results were analyzed.Results 62.30％of the data for this survey was provided by the father,possibly due to a Chinese tradition where mothers were confined at home during confinement after their child's discharge,making it inconvenient for them to go out.The educational level of parents was mainly undergraduate or above,with an age of 30.55±5.07 years old,mainly middle-aged and young;The top 5 scores for continuity of care content requirements were:reminder for follow-up visits(4.39±0.08)points,discharge medication guidance(4.35±0.92)points,health assessment(4.29±0.94)points,disease-related knowledge education(4.28±0.95)points,specialized nursing(4.17±1.05)points and basic nursing guidance(4.17±1.04)points;The top four scores of parents'demands for extended nursing channels were:telephone follow-up 2673(85.45％),discharge education 2529(80.85％),community two-way referral 2390(76.41％),and health education network platform 2271(72.60％)(such as WeChat official account,forum,Tiktok live broadcast);Family members hope that 2340 doctors(74.81％)and 1 764 hospital nurses(56.39％)were still the main executors of extended services provided by the hospital;After discharge,if necessary due to the condition,medical staff would come to your doorstep to provide corresponding medical care services.Patients agreed to pay 2759 cases(88.20％)according to the price standard,with the majority agreeing to pay 2 189 cases(69.98％)for consultation fees,2057 cases(65.76％)for material fees and 1 997 cases(63.84％)for diagnosis,treatment,and nursing fees.Conclusion Providing continuous extended care services during and after the discharge of newborns can reduce their readmission rate,promote physical development,and reduce complications.With the development of medical technology and information technology,parents of newborns have an increasing demand for extended care services,and it is imperative to carry out extended care services.

Objective To analyze the clinical characteristics of collagenous gastritis (CG) and provide evidence for the precise diagnosis and treatment of CG.Methods Published case reports and case series were collected from PubMed,CNKI,and Wanfang Med Online with the key words of collagenous gastritis,collagenous gastroduodenitis,collagenous gastrointestinal diseases,and gastric mucosal nodules.The demographic and clinical information of each case was collected.Results According to the extent of collagen deposition in the digestive tract,94 CG cases included in this study were assigned into upper digestive tract (UDT)-CG,total digestive tract (TDT)-CG and other groups.The UDT-CG group included 52 cases (57.69% females and 42.31% males) with a median age of 14.50 (11.00,25.75) years old.There were 17 cases in the TDT-CG group,including 70.59% females and 29.41% males,with a median age of 15.00 (9.50,48.50) years old.The other group contained 25 cases,(64.00% females and 36.00% males) with a median age of 25.00 (15.50,59.50) years old.The main clinical manifestations in the UDT-CG group were anemia (59.62%) and diarrhea (17.31%),and those in the TDT-CG group were anemia (29.41%) and diarrhea (94.12%).The nodular appearance of gastric mucosa was observed in 75.00% cases in the UDT-CG group and 35.29% cases in the TDT-CG group.In the initial treatment,symptomatic therapy and hormonal therapy respectively relieved the symptoms in 75.00% (30/40) and 100% (3/3) cases in the UDT-CG group and 57.14% (4/7) and 83.33% (5/6) cases in the TDT-CG group.In the retreatment,symptomatic therapy and hormone therapy respectively achieved the remission rates of 100.00% (3/3) and 88.89% (8/9) in the UDT-CG group and 80.00% (4/5) and 66.67% (2/3) in the TDT-CG group.Conclusions CG,a rare disease of gastric collagen deposition,mainly occurs in young patients,and females are more susceptible than males.The clinical manifestations of CG are nonspecific,and anemia,abdominal pain,diarrhea,weight loss,and gastrointestinal bleeding are the common symptoms of CG.Nodular appearance of gastric mucosa is a relatively specific endoscopic feature of CG.There is no standardized treatment for CG.Symptomatic treatment is commonly adopted to improve the quality of life of the patients,and hormones can be added when necessary.
Male ; Female ; Humans ; Quality of Life ; Gastritis/diagnosis* ; Gastric Mucosa ; Collagen ; Anemia/etiology* ; Diarrhea/complications*

A 61-year-old male patient with diffuse large B-cell lymphoma received BeEAM pre-treatment measures such as bendamustine, cytarabine, etoposide, and melphalan for autologous hematopoietic stem cell transplantation. Anti-infective treatments such as aciclovir, posaconazole, levofloxacin, biapenem, and vancomycin were administered successively. Before the pre-treatment of transplantation, the patient′s blood potassium was 4.1 mmol/L, and after 7 days of treatment with posaconazole and levofloxacin, the blood potassium was 3.4 mmol/L. Intravenous and oral potassium supplementation was administered. After 5 days of potassium supplement, the patient developed atrial fibrillation, with blood potassium level of 3.3 mmol/L. After continuing potassium supplement for 7 days, his blood potassium level remained 3.0 mmol/L. After excluding causes of other drugs, it was considered that hypokalemia might be related to posaconazole. The posaconazole was discontinued and switched to voriconazole; 3 days later, his blood potassium returned to 4.2 mmol/L. During a 3-month of follow-up, multiple examinations showed that the blood potassium levels were within the reference range.

A 61-year-old male patient with diffuse large B-cell lymphoma received BeEAM pre-treatment measures such as bendamustine, cytarabine, etoposide, and melphalan for autologous hematopoietic stem cell transplantation. Anti-infective treatments such as aciclovir, posaconazole, levofloxacin, biapenem, and vancomycin were administered successively. Before the pre-treatment of transplantation, the patient′s blood potassium was 4.1 mmol/L, and after 7 days of treatment with posaconazole and levofloxacin, the blood potassium was 3.4 mmol/L. Intravenous and oral potassium supplementation was administered. After 5 days of potassium supplement, the patient developed atrial fibrillation, with blood potassium level of 3.3 mmol/L. After continuing potassium supplement for 7 days, his blood potassium level remained 3.0 mmol/L. After excluding causes of other drugs, it was considered that hypokalemia might be related to posaconazole. The posaconazole was discontinued and switched to voriconazole; 3 days later, his blood potassium returned to 4.2 mmol/L. During a 3-month of follow-up, multiple examinations showed that the blood potassium levels were within the reference range.

There is a high prevalence rate of malnutrition in patients with end-stage liver disease, which often promotes disease progression and has a negative impact on the prognosis of patients. This article briefly describes the etiology of malnutrition in end-stage liver disease and introduces the research advances in nutrition screening, evaluation, and treatment in end-stage liver disease in China and globally, hoping to provide inspiration for nutritional support in patients with end-stage liver disease in China.