Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the effect of Scutellarin(Scu)regulating miR-26a-3p/Survivin molecular axis on myocardial ischemia/reperfusion injury(MIRI)in rats and its mechanism.Methods Fifty SD rats were randomly divided into sham group,model group,scutellarin group(Scu),miR-26a-3p agomir group(agomir)and scutellarin+miR-26a-3p agomir group(Scu+agomir)with 10 rats in each group.The animal model of MIRI was established by ligating the anterior descending coronary artery.The rats in each group were given 20 mg/kg Scu or 10 nmol agomir before and during operation,respectively,and the rats in sham group and model group were given the same amount of solvent.At 48 h after operation,the cardiac function of rats was examined by echocardiography.The pathological changes of myocardial tissue were detected by HE staining.The levels of myocardial injury markers creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH)and cardiac troponin I(cTnI)in serum and the contents of oxidative markers Malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in myocardial tissue were detected by biochemical kit.The apoptosis of rat cardiomyocytes was detected by TUNEL staining.The mRNA expression levels of miR-26a-3p and Survivin in rat myocardium were detected by qRT-PCR.Expression levels of Survivin,cyclin-dependent kinase inhibitor(p21)and cleaved-caspase 3 were detected by Western blot.Results Compared with sham group,the pathological damage of myocardial tissue in the model group was serious,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly increased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly decreased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly increased(P<0.01),while the SOD and GSH-Px levels significantly decreased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly increased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly decreased(P<0.01).Compared with model group,the pathological injury of myocardium in Scu group was significantly improved,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly decreased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly increased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly decreased(P<0.01),while the SOD and GSH-Px levels significantly increased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly decreased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly increased(P<0.01).However,intervention with miR-26a-3p agomir could significantly reverse the improvement effect of Scu on MIRI in rats.Conclusion Scu can improve cardiac function and myocardial injury and inhibit myocardial cell apoptosis in MIRI rats,and its mechanism may be related to the regulation of miR-26a-3p/Survivin molecular axis.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To investigate the imaging characteristics of clear cell acanthoma (CCA) by dermoscopy and reflectance confocal microscopy (RCM) .Methods:A retrospective analysis was conducted on 12 patients diagnosed with CCA through histopathological examination at the Department of Dermatology, Wuhan No.1 Hospital, from 2020 to 2024. Dermoscopic and RCM features of these cases were summarized.Results:Among the 12 CCA patients, 3 were males and 9 were females, and they were aged 50.08 ± 10.43 years. Clinically, CCA lesions were typically presented as red or brown papules or nodules with well-defined borders, ranging in diameter from 3 mm to 2 cm. Histopathological examination showed that the tumor manifested as psoriasiform or papillary hyperplasia with a thickened spinous layer and a distinct boundary surrounded by the normal skin; proliferating cells were larger with lightly stained cytoplasm; neutrophil infiltration was observed in the epidermis, and vascular dilation was observed in the dermal papillae and superficial dermis; periodic acid-Schiff staining revealed abundant glycogen in the cells. In 10 patients examined by dermoscopy, dotted, globular, or glomerular vessels were arranged in a beaded pattern in all the 10 patients, and collar-like scales were seen at the edges of the lesions in 6 patients. In 6 patients examined by RCM, RCM images all revealed epidermal hyperplasia, thickened spinous layers, large keratinocytes with enlarged nuclei and abundant cytoplasm that blended in with the intercellular demarcations, disordered honeycomb structure of the epidermis, and dilation and up-thrust of blood vessels in the dermal papillae and superficial dermis; segmented cell infiltration was observed in the epidermis of 4 patients. As measured, the longest diameters of cells in the upper part of the CCA spinous layer ranged from 30.25 μm to 35.13 μm; the longest diameters of spinous layer cells at the CCA follicles (19.39 ± 2.93 μm) were significantly lower than those of the surrounding spinous layer cells (30.95 ± 5.66 μm, t = 5.73, P < 0.001) . Conclusions:CCA presents a distinctive vascular pattern on dermoscopy, and the majority of histological features can be visualized by RCM. Dermoscopy and RCM can be relatively reliable auxiliary diagnostic methods for CCA.

This article summarizes the experience of providing remote nursing care for a pediatric patient with severe burns using augmented reality(AR)technology.Key nursing points include:to establish a remote management team to enhance multidisciplinary collaboration;to conduct remote nursing ward rounds to provide real-time guidance for clinical nursing practice;to remotely guide PICC(Peripherally Inserted Central Catheter)insertions and conduct precise fluid management;to remotely assess ward environments and provide guidance on disinfection and isolation measures;to alleviate pediatric pain through comprehensive management measures.After meticulous care and treatment,the patient's condition stabilized after 23 days,and the patient was transferred to a specialized hospital for continued treatment requiring skin grafting.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective To investigate the effect of forsythigenin on the malignant progression of lung cancer cells by regulating the cyclic adenosine monophosphate/exchange protein directly activated by cAMP1/Ras-associated protein 1(cAMP/EPAC1/RAP1)signaling pathway.Methods Lung cancer cell line A549 was cultured in vitro and grouped into the control group,the low dose forsythigenin group(25 mg/L),the medium dose forsythigenin group(50 mg/L),the high dose forsythigenin group(100 mg/L),the high dose forsythigenin+specific increase in intracellular cAMP content(pertussis toxin PTX)group(100 mg/L forsythigenin+5 μmol/L PTX)and high dose forsythigenin+EPAC1 antagonist(ESI-09)group(100 mg/L forsythigenin+1.5 μmol/L ESI-09).CCK-8 experiment was applied to detect cell proliferation.Scratch test was applied to detect cell migration.Flow cytometry was applied to detect cell apoptosis.Transwell was applied to detect cell invasion.ELISA method was applied to detect cAMP level in cell supernatant.Western blot assay was applied to detect expression levels of cAMP/EPAC1/RAP1 signaling pathway proteins and apoptotic proteins[B lymphoblastoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)].Results Compared with the control group,the OD450 value of A549 cells,number of cell invasions,scratch healing rate,level of cAMP,expression levels of Bcl-2,EPAC1 and RAP1 proteins were significantly reduced in the low dose,medium dose and high dose forsythigenin groups,and the expression of Bax protein and the rate of cell apoptosis were significantly increased in a dose-dependent manner(P＜0.05).Compared with the high-dose forsythigenin group,the OD450 value of A549 cells,scratch healing rate,number of cell invasions,level of cAMP,expression levels of Bcl-2,EPAC1 and RAP1 proteins were obviously increased in the high-dose forsythigenin+PTX group,the expression of Bax protein and the apoptosis rate were obviously reduced(P＜0.05).Levels of all indexes in the high dose forsythigenin+ESI-09 group were opposite.Conclusion Forsythigenin inhibits proliferation,migration,and invasion of A549 cells and promotes apoptosis by down-regulating the cAMP/EPAC1/RAP1 signaling pathway.

Objective:To investigate the imaging characteristics of clear cell acanthoma (CCA) by dermoscopy and reflectance confocal microscopy (RCM) .Methods:A retrospective analysis was conducted on 12 patients diagnosed with CCA through histopathological examination at the Department of Dermatology, Wuhan No.1 Hospital, from 2020 to 2024. Dermoscopic and RCM features of these cases were summarized.Results:Among the 12 CCA patients, 3 were males and 9 were females, and they were aged 50.08 ± 10.43 years. Clinically, CCA lesions were typically presented as red or brown papules or nodules with well-defined borders, ranging in diameter from 3 mm to 2 cm. Histopathological examination showed that the tumor manifested as psoriasiform or papillary hyperplasia with a thickened spinous layer and a distinct boundary surrounded by the normal skin; proliferating cells were larger with lightly stained cytoplasm; neutrophil infiltration was observed in the epidermis, and vascular dilation was observed in the dermal papillae and superficial dermis; periodic acid-Schiff staining revealed abundant glycogen in the cells. In 10 patients examined by dermoscopy, dotted, globular, or glomerular vessels were arranged in a beaded pattern in all the 10 patients, and collar-like scales were seen at the edges of the lesions in 6 patients. In 6 patients examined by RCM, RCM images all revealed epidermal hyperplasia, thickened spinous layers, large keratinocytes with enlarged nuclei and abundant cytoplasm that blended in with the intercellular demarcations, disordered honeycomb structure of the epidermis, and dilation and up-thrust of blood vessels in the dermal papillae and superficial dermis; segmented cell infiltration was observed in the epidermis of 4 patients. As measured, the longest diameters of cells in the upper part of the CCA spinous layer ranged from 30.25 μm to 35.13 μm; the longest diameters of spinous layer cells at the CCA follicles (19.39 ± 2.93 μm) were significantly lower than those of the surrounding spinous layer cells (30.95 ± 5.66 μm, t = 5.73, P < 0.001) . Conclusions:CCA presents a distinctive vascular pattern on dermoscopy, and the majority of histological features can be visualized by RCM. Dermoscopy and RCM can be relatively reliable auxiliary diagnostic methods for CCA.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Objective To investigate the effect of forsythigenin on the malignant progression of lung cancer cells by regulating the cyclic adenosine monophosphate/exchange protein directly activated by cAMP1/Ras-associated protein 1(cAMP/EPAC1/RAP1)signaling pathway.Methods Lung cancer cell line A549 was cultured in vitro and grouped into the control group,the low dose forsythigenin group(25 mg/L),the medium dose forsythigenin group(50 mg/L),the high dose forsythigenin group(100 mg/L),the high dose forsythigenin+specific increase in intracellular cAMP content(pertussis toxin PTX)group(100 mg/L forsythigenin+5 μmol/L PTX)and high dose forsythigenin+EPAC1 antagonist(ESI-09)group(100 mg/L forsythigenin+1.5 μmol/L ESI-09).CCK-8 experiment was applied to detect cell proliferation.Scratch test was applied to detect cell migration.Flow cytometry was applied to detect cell apoptosis.Transwell was applied to detect cell invasion.ELISA method was applied to detect cAMP level in cell supernatant.Western blot assay was applied to detect expression levels of cAMP/EPAC1/RAP1 signaling pathway proteins and apoptotic proteins[B lymphoblastoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)].Results Compared with the control group,the OD450 value of A549 cells,number of cell invasions,scratch healing rate,level of cAMP,expression levels of Bcl-2,EPAC1 and RAP1 proteins were significantly reduced in the low dose,medium dose and high dose forsythigenin groups,and the expression of Bax protein and the rate of cell apoptosis were significantly increased in a dose-dependent manner(P＜0.05).Compared with the high-dose forsythigenin group,the OD450 value of A549 cells,scratch healing rate,number of cell invasions,level of cAMP,expression levels of Bcl-2,EPAC1 and RAP1 proteins were obviously increased in the high-dose forsythigenin+PTX group,the expression of Bax protein and the apoptosis rate were obviously reduced(P＜0.05).Levels of all indexes in the high dose forsythigenin+ESI-09 group were opposite.Conclusion Forsythigenin inhibits proliferation,migration,and invasion of A549 cells and promotes apoptosis by down-regulating the cAMP/EPAC1/RAP1 signaling pathway.