Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.

Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P＜0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P＜0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P＜0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

In recent years, there has been an increasing trend regarding the incidence of anaphylaxis among children in China. Despite the existence of relevant diagnosis and treatment guidelines for regulation, due to reasons such as uneven allocation of medical resources, there are still many problems in the specific implementation process of primary health care institutions, and these problems may lead to untimely and irregular handling of allergic reactions, thereby increasing the risk for pediatric patients. This review discussed the related issues existing about the diagnosis and treatment of anaphylaxis in children in primary health care institutions.

Membranous nephropathy(MN)is the predominant cause of primary nephrotic syn-drome(NS)among adults.The identification of PLA2R as target antigen has brought about a pro-found transformation in the management of MN,offering a basis for the utilization of B-cell deplet-ing agents such as rituximab(RTX).The question of whether early intervention targeting antibodies can effectively impede the progression of MN,contrib-uting to enhanced disease control and long-term renal outcomes for patients,remains further explo-ration.We analyzed demographic data,laboratory parameters,and renal involvement in 13 patients with PLA2R antibody-related MN who received at least one RTX treatment at our center from Octo-ber 2019 to March 2023.Early-stage medium-to-high-risk MN was defined as baseline or admission anti-PLA2R antibody levels exceeding 50 RU/mL,ex-cluding patients who already presented with ne-phrotic syndrome at baseline.The median duration of MN at the initiation of the first RTX treatment was 4.1 months(IQR 1-7.7),and the median follow-up time after RTX therapy was 27 months(IQR 23-45).All patients had commenced renin-angiotensin system inhibitors before receiving RTX.Following RTX therapy,none of the 13 patients progressed to NS during the follow-up period,and 12 patients achieved complete or partial remission at the 2-year follow-up or the last visit.No deaths,severe infections,or other serious adverse reactions oc-curred during the follow-up period.In conclusion,RTX demonstrates favorable efficacy and safety in early-stage,medium-to-high-risk MN patients.Initi-ating antibody clearance therapy in these patients may be beneficial for long-term disease control and distant renal outcomes.

Objective To investigate the status quo of pain empathy of nursing students and its influencing factors in DSecond Affiliated Hospital of Naval Medical University,so as to provide the basis for intervention education and improve their pain empathy.Methods A survey was conducted in 230 nursing students in The Second Affiliated Hospital of Naval Medical University from July 2021 to April 2022 by self-made demographic data questionnaire,Chinese version of empathy for pain scale(EPS-C),short-egnaminnenav barndoms uppfostran for Chinese(s-EMBU-C),and care ability inventory(CAI)scale.Results The total score of pain empathy of the nursing students was 2.83±0.68.The score of the body and mind discomfort reactions was 2.69±0.75 and the score of empathy reactions was 3.24±0.69.The results of multivariate analysis showed that gender,education level,being only child or not,liking watching violent films or not,and parental rearing pattern were the influencing factors for pain empathy(all P<0.05).Conclusion The nursing students have a medium level of empathy for pain in this military hospital.Nursing educators should develop targeted intervention programs for nursing students with different characteristics according to the actual situation of military hospitals,and guide them to establish good pain empathy.

Erythroferrone is a newly discovered and important factor regulating iron homeostasis and mainly produced by erythroblasts. Erythroferrone responds to the increase of erythropoietin and regulates plasma iron level, along with the absorption and utilization of iron via hepcidin, which plays an important role in the pathophysiology of iron metabolism-related diseases. Erythropoietin deficiency and iron metabolism disturbance are prominent features of renal anemia complicated with chronic kidney disease. Accordingly, erythroferrone is corresponding to the pathogenesis, treatment and prognosis of renal anemia. The in-depth study contributes to the further understanding of the mechanism related to iron metabolism disorder, and erythroferrone is also expected to be used as a valuable biomarker in the detection of renal anemia and the evaluation of therapeutic response. The article systematically reviews the physiological function of erythroferrone and its research progress in iron metabolism and renal anemia.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*