The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective To explore the influencing factors of depression risk in elderly patients with hypertension and construct and validate a nomogram prediction model.Methods A total of 869 elderly patients with hypertension were selected from national survey database of the China Health and Retirement Longitudinal Study(CHARLS)in 2018.Multivariate Logistic regression analysis was used to identify the risk factors for depression in elderly patients with hypertension,and a nomogram prediction model was constructed.The accuracy and effectiveness of the model were validated by the Hosmer-Lemeshow(H-L)goodness-of-fit test,the area under the curve(AUC)of the receiver oper-ating characteristic(ROC)curve,and the calibration curve.Results The incidence of depression in elderly patients with hypertension was 47.18％.Factors influencing the risk of depression included rural residence(OR=2.191,P＜0.05),impaired basic activities of daily living(BADL)(OR=2.338,P＜0.05),impaired instrumental activitiesofdaily living(IADL)(OR=1.674,P＜0.05),poor life satisfaction(OR=7.348,P＜0.05),fair self-rated health(OR=0.441,P＜0.05),good self-rated health(OR=0.259,P＜0.05),and sleep duration of 6 to 9 hours(OR=0.510,P＜0.05).The AUC of the ROC curve was 0.795,the slope of the calibration curve was close to 1,and the H-L goodness-of-fit test yielded x2=5.074.The validation set showed an AUC of 0.703.Conclusion The prediction model established in this study has high accuracy and discriminative ability.Healthcare professionals can take effective preventive measures based on individual patient factors.

Patients with metabolic syndrome(MS)are at potential risk for cardiovascular disease and have received increasing public and medical attention.Studies have shown that regular physical exercise can effectively regulate meta-bolic indicators such as blood pressure,blood sugar and blood lipids,and play a positive role in reducing the risk of cardio-vascular disease and improving the prognosis of patients.Exercise intensity has been identified as the most important as-pect in reducing the risk of cardiovascular death and all-cause mortality in exercise intervention.Therefore,the design of exercise prescription which is both scientific and satisfying individual differences has become the focus of research.Most of the current clinical studies are based on the percentage of exercise intensity as the basis for the formulation of standard-ized exercise prescription for MS patients,while the studies on the individualized threshold of exercise intensity based on cardiopulmonary exercise test(CPET)are still few.CPET has shown that individualized exercise prescription can effec-tively reduce body composition index,blood pressure and blood glucose,improve cardiorespiratory function,exercise en-durance and quality of life in MS patients.This paper reviewed the development of individualized exercise programs with different intensification according to threshold indexes in CPET,analyzed the intervention effects and possible mechanisms for MS patients and subgroups,and provided certain reference for the formulation and implementation of personalized exer-cise prescriptions for MS patients,and also provided references for in-depth research on individualized exercise intervention for MS.

Objective: To examine the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression among healthcare workers, so as to provide the reference for developing effective psychological intervention. Methods: The clinical doctors, nurses and public health professionals were selected using the stratified random cluster sampling method from hospitals, disease prevention and control centers, and health departments in five cities in Shandong Province, including Qingdao, Jinan, Rizhao, Jining and Liaocheng in January 2023. Basic information, mindfulness level, resilience and symptoms of anxiety and depression among healthcare workers were collected using general demographic questionnaires, the 5-item Mindful Attention Awareness Scale, 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder Scale and Patient Health Questionnaire, respectively. The Process program was used to analyze the mediating effects of mindfulness level on resilience and symptoms of anxiety and depression. Results: A total of 1 836 healthcare workers were investigated, including 472 males (25.71%) and 1 364 females (74.29%), and the median age was 39 (interquartile range, 12) years. There were 629 clinical doctors (34.26%), 963 nurses (52.45%) and 244 public health professionals (13.29%). The median scores of mindfulness level and resilience were 22 (interquartile range, 7) and 20 (interquartile range, 4) points, respectively. The detection rates of anxiety and depression symptoms were 49.78% and 72.28%, respectively. The mediation analysis showed that mindfulness level exerted a partial mediating effect between resilience and anxiety symptoms (β=-0.510, P<0.001), with a direct effect value of -0.130 and a mediating effect value of -0.046, and the mediating effect accounted for 26.14% of the total effect; mindfulness level also exerted a partial mediating effect between resilience and depression symptoms (β=-0.575, P<0.001), with a direct effect value of -0.120 and a mediating effect value of -0.052, and the mediating effect accounted for 30.23% of the total effect. Conclusion Mindfulness level plays a mediating effect between resilience and symptoms of anxiety and depression among healthcare workers.

Objective:The purpose of this study was to examine the clinical features and initial treatment outcomes of elderly individuals with idiopathic membranous nephropathy.Methods:This study retrospectively analyzed the clinical characteristics and therapeutic effect of hospitalized patients aged 60 years or older with renal-biopsy-proven idiopathic membranous nephropathy for at least one year.Results:This study enrolled a total of 91 elderly patients with IMN, consisting of 51 males(56.0%)and 40 females(44.0%). The median age of the patients was 67 years.The urinary protein creatinine ratio(uPCR)and urinary albumin creatinine ratio(uACR)of the patients were 4 454.3 mg/g and 2 258.5 mg/g, respectively.The median 24-hour urinary protein and urinary albumin levels were 5 098.2 mg/24 h and 2 800.6 mg/24 h, respectively.The average estimated glomerular filtration rate(eGFR)was(60.5±20.4)ml·min -1·1.73 m -2.Out of the total of 61 patients, 67.0% achieved remission, including complete and partial remission, within a year of renal biopsy.The levels of uPCR and uACR were significantly higher in the non-remission group compared to the remission group(5 462.5 vs.2 271.1 mg/g, P<0.001; 2 774.4 vs.1 320.0 mg/g, P=0.001). Additionally, the levels of 24h urinary protein and urinary albumin were significantly higher in the non-remission group compared to the remission group(6 526.4 vs.3 210.4 mg/g, P=0.002; 3 067.7 vs.2 102.4 mg/g, P=0.007). The remission group had a higher proportion of patients receiving immunosuppressive therapy(85.2% vs.33.3%, P<0.001). The remission rates were higher in patients treated with glucocorticoid combined with cyclophosphamide, glucocorticoid combined with calcineurin inhibitors, or glucocorticoid combined with mycophenolate mofetil compared to those receiving conservative treatment(88.2% vs.31.0%, P=0.001; 80.0% vs.31.0%, P<0.001; 100.0% vs.31.0%, P=0.007). There was no significant difference in remission rate between the three immunosuppressive therapy groups( P>0.05). However, upon further analysis, it was found that the levels of uPCR, uACR, and serum cystatin C(CysC)were higher in the immunosuppressive therapy groups compared to conservative treatment.Additionally, serum total protein and albumin were lower in the immunosuppressive therapy groups, and these differences were statistically significant( P<0.05). Conclusions:The majority of elderly patients diagnosed with IMN have multiple comorbidities.For those at high risk with elevated urinary protein levels, early initiation of immunosuppressive therapy may lead to a higher initial urinary protein remission rate.Therefore, it is advisable to develop individualized treatment plans for elderly patients with IMN based on their clinical characteristics, as well as the risks and benefits associated with immunosuppressive therapy.

  Objective  To understand the current status of surgical treatment for hemophilia osteoarthropathy (HO) in China.  Methods  Using an online questionnaire, select domestic hospitals that partici-pated in the compilation of the 'Guideline for perioperative management of hemophilia patients undergoing orthopaedic surgery in China ', in addition to members of the National Joint Surgery Group, and the Orthopedic Branch of the Chinese Medical Association for targeted investigation and analysis.  Results  A total of 17 domestic hospitals were included, all of which were general hospitals. Hospitals that started HO surgery treatment before 2000 accounted for 35.29%. A total of 3057 surgical cases of HO were reported by those hospitals. The most commonly performed surgical procedures were hip and knee joint replacement. The most commonly used coagulation factor replacement regimen was recombinant coagulation factor preparation. Ten hospitals reported finding patients with transfusion-related infectious diseases. Bleeding and hematoma formation were the most frequently reported surgical complications. Excessive length of hospital stay and high economic costs were the most frequently reported problems.  Conclusions  Surgical treatment for HO in 17 hospitals is mainly carried out in some large comprehensive medical centers in the eastern region. Compared with the patient base, the popularity and number of surgeries are still relatively insufficient. It is necessary to further standardize the treatment system by standardizing factor replacement and strengthening rehabilitation to improve surgical treatment outcomes.

Objective:To screen the causative genes of five families with branchio-oto-renal syndrome (BORS) or branchio-oto syndrome(BOS) and to analyze the phenotypic characteristics and clinical management strategies of patients.Methods:Five families with BORS/BOR from December 2018 to September 2021 were recruited, information of patients, including family history and medical history, was collected, and genealogies were drawn. The examinations concerning audiology, nephrology, and radiology were performed on the affected individuals. Peripheral blood was obtained for DNA extraction, then next-generation sequencing technology was used to screen candidate variants associated with BORS/BOS. Based on patient′s clinical results, the appropriate interventions were recommended and implemented.Results:Eight individuals were diagnosed with BOS or BORS. Of the eight patients, all had hearing loss, preauricular pits and ear malformations, and only four presented with branchial cleft fistulae or cysts. Except for two patients(5-I-2, 5-II-2) who did not undergo renal examination, the remaining six lacked renal abnormalities. Genetic analysis identified four likely pathogenic or pathogenic EYA1 variants (c.1715G>T, c.1140+1G>A, c.639G>C, c.1475+1G>C; NM_000503.6), and c.1715G>T was first reported in this study. Middle ear ossicular reconstruction was performed in 1-II-2,2-I-2 and 3-II-2, but did not yield the expected results; then hearing aids and cochlear implantation were recommended and achieved satisfactory results. Conclusions:Next-generation sequencing technology facilitates the diagnosis and genetic counseling of BORS/BOS. Hearing loss, preauricular pits, ear malformations and branchial cleft fistulae or cysts are the most common manifestations of patients in this study. Middle ear surgeries for improving hearing loss may have some limitations in BORS/BOS patients, and hearing aids and cochlear implantation can contribute to hearing gains.

Objective:To evaluate the clinical efficacy of the bridge pedicled transplantation of medial leg fascial flap combined with medial hemisoleus muscle flap for contralateral leg soft tissue defect.Methods:Between January of 2012 and January of 2018, 12 patients with soft tissue defect of the leg were treated with bridge pedicled transplantation of contralateral medial leg fascial flap combined with medial hemisoleus muscle flap by posterior tibial artery. There were 9 males and 3 female, aged from 19 to 53 years (mean, 35 years). The size of the soft-tissue defects ranged from 12 cm×8 cm to 18 cm×9 cm. The immediate coverage of the fascial and muscle flaps and vessel pedicle were repaired by a meshed split-thickness skin graft. The donor site was closed directly. After the transplantation of the one pedicle and two flaps survived, vascular pedicle was cut off.Results:All the fascial and muscle flaps survived completely. No clinical vascular deficiency was found on the fascial and muscle flaps postoperatively. One case developed distal muscle flap small skin graft necrosis, and spontaneous healed after 2 weeks of dressing change. Follow-up period ranged from 2.5 to 4.5 years (mean 3.8 years). A good contour was confirmed both at the recipient and donor sites. Satisfactory clinical results were obtained in this series.Conclusion:This method is suitable for the treatment of soft tissue defects of the leg with only one major blood vessel, which reduces the damage to the donor site.

Objective:To evaluate the efficacy of the repairing anterior tibial adjacent double wounds by transposition with single-pedicle two flaps of the medial head of gastrocnemius.Methods:Between January of 2012 and January of 2018, 10 patients with the anterior tibial adjacent double wounds (7 males and 3 female, aged from 21 to 45 years) were treated by transposition with single-pedicle two flaps of the medial head of gastrocnemius. The size of the soft-tissue defects ranged from 2.0 cm×2.5 cm to 4.5 cm×4.0 cm. The medial head of the gastrocnemius was divided into two flaps with a single pedicle to repair two adjacent wounds of the anterior tibial. The muscle flaps were immediately covered by a meshed split-thickness skin graft, and the wound in donor site was closed directly.Results:All the muscle flaps survived completely. No clinical vascular deficiency was found on the muscle flaps postoperatively. Small wound dehiscence was developed in one patient and spontaneously healed 2 weeks after dressing change. Patients were followed up for 2.0 to 4.5 years. A good contour was confirmed at the recipient and donor sites. Satisfactory clinical results were obtained in this series.Conclusion:This method is suitable for the repair of two adjacent small wounds of the anterior tibial which can reduce the damage to the donor site.

Objective: To investigate the number and distribution of dendritic cells (DCs), macrophages and M2 macrophages in renal tissues of patients with IgA nephropathy (IgAN) and their correlation with clinicopathological parameters, and explore its role in the progression of IgAN. Methods: Renal tissue samples from 42 patients aged ≥18 years with IgAN were collected by kidney biopsy in Guangdong Provincial People's Hospital from January 2018 to June 2018. The patients were divided into different groups according to Oxford classification and Lee grade classification criteria. The distribution and number of DCs (CD209), macrophages (CD68) and M2 macrophages (CD68 and CD206) were detected by immunohistochemistry. Spearman correlation test was used to analyze the correlation between the number of DCs and macrophages in renal tissues and clinical pathological parameters. Results: The number of DCs in the glomeruli of the M1, T0 and C1 groups increased significantly compared with the M0, T1 and C0 groups, and the number of DCs in the renal interstitium of the T1 group increased significantly compared with the T0 group (all P<0.05). The number of glomerular macrophages in group C1 was significantly higher than that in group C0. The number of macrophages in S1, T1 and Lee IV-V tubulointerstitial groups was significantly higher than that in S0, T0 and Lee II-III groups (P<0.05). The number of M2 macrophages in the S1, T1 and Lee IV-V groups was significantly higher in the tubulointerstitial group than in the S0, T0 and Lee II-III groups (all P<0.05). The blood urea nitrogen, serum creatinine and 24 h urine protein levels in the T1 and Lee IV-V groups were significantly higher than those in the T0 and Lee II-III groups, and the serum albumin levels in the Lee IV-V group were significantly lower (all P<0.05). Spearman correlation analysis showed that the number of DCs in renal interstitium was positively correlated with the proportion of tubulointerstitial fibrosis. There were a positive correlation between the proportion of glomerular segmental sclerosis and tubulointerstitial fibrosis and renal interstitial macrophages and M2 macrophages. The number of M2 macrophages was positively correlated with serum creatinine and 24 h urine protein (both P<0.05). Conclusions The number of DCs and M2 macrophages in kidneys are positively correlated with the clinicopathological features of IgAN patients, which indicates that they may be associated with disease progression.