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Iron is crucial for cell DNA synthesis and repair, but an excess of free iron can lead to oxidative stress and subsequent cell death. Although several studies suggest that cancer cells display characteristics of ‘Iron addiction’, an ongoing debate surrounds the question of whether iron can influence the malignant properties of ovarian cancer. In the current study, we initially found iron levels increase during spheroid formation. Furthermore, iron supplementation can promote cancer cell survival, cancer spheroid growth, and migration; vice versa, iron chelators inhibit this process. Notably, iron reduces the sensitivity of ovarian cancer cells to platinum as well. Mechanistically, iron downregulates DNA homologous recombination (HR) inhibitor polymerase theta (POLQ) and relieves its antagonism against the HR repair enzyme RAD51, thereby promoting DNA damage repair to resist chemotherapy-induced damage. Additionally, iron tightly regulated by ferritin (FTH1/FTL) which is indispensable for iron-triggered DNA repair. Finally, we discovered that iron chelators combined with platinum exhibit a synergistic inhibitory effect on ovarian cancer in vitro and in vivo. Our findings affirm the pro-cancer role of iron in ovarian cancer and reveal that iron advances platinum resistance by promoting DNA damage repair through FTH1/FTL/POLQ/RAD51 pathway. Our findings highlight the significance of iron depletion therapy, revealing a promising avenue for advancing ovarian cancer treatment.

Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1α in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1α were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1α to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1α. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1α expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1α was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1α, contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1α axis may serve as a potential therapeutic target for RSA.

Background Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. Results To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS -mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB 2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. Conclusions Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

Purpose Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population. Methods and Results This study included 165 patients with PMMC in the Chinese population. We used the Kaplan‐Meier method to build the survival curve, and the log‐rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy‐based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk. Conclusion After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient‐specific treatment options need to be further discussed.

Ovarian mucinous cystic tumors may be associated with various types of mural nodules, which can be classified as benign or malignant (anaplastic carcinoma, sarcoma, carcinosarcoma). However, anaplastic malignant nodules have rarely been reported. Here, we present a case of a 35-year-old woman who presented with abdominal discomfort. Ultrasonography showed a large cystic mass in the pelvic and abdominal cavities measuring 337 × 242 mm. Abdominal computed tomography revealed upper anterior and posterior uterine pelvic cystic lesions based on multiple nodule partition walls and classes. During hospitalization, the patient underwent exploratory laparotomy, which revealed a poorly differentiated ovarian malignant tumor, and subsequent surgical excision was performed. The pathological analysis of the surgical samples of the right ovary revealed a mucinous ovarian tumor, while the mural nodules were classified as anaplastic carcinoma. After surgery, the patient started receiving chemotherapy. Unfortunately, the patient died 6 months later. Mucinous tumor occurring with an anaplastic carcinoma is rare, and the current diagnostic methods are not sufficient in providing an early and accurate diagnosis. Most patients are already in the advanced stage upon diagnosis and combined with poorly differentiated pathological features, the prognosis is extremely poor. Clinicians need to improve the clinical evaluation before surgery and conduct preoperative preparation and communication to improve the prognosis of patients as much as possible.

Objective This study aims to investigate the impacts of CO 2 pneumoperitoneum on the growth of ovarian cancer in nude mice and the expression of tumor metastasis suppressor gene (NM23-H1) and matrix metalloproteinase -2 (MMP-2) in SKOV-3 ovarian cancer cell line cancer tissue. Method Forty five  nude mice were used to establish ovarian cancer xenograft models by intraperitoneal injection of human ovarian cancer cell line SKOV-3. Murine xenograft models were divided into four groups: control group (only anesthetized for 0.5 h), laparotomy group (laparotomy for 0.5 h), CO 2 pneumoperitoneum of 0.5 h, and CO 2 pneumoperitoneum of 1 h group. Mice were killed after 12 weeks to observe intraperitoneal tumor growth and detected mRNA expression of NM23-H1 and MMP-2 in tumor tissues by RT-PCR. Result Our data show that xenograft tumors grew faster in the CO 2 pneumoperitoneum groups than that in control and laparotomy groups and even faster in the CO 2 pneumoperitoneum of 1 h group. The mRNA expression of NM23-H1 in CO 2 pneumoperitoneum groups was significantly lower than that in control group and laparotomy group ( P  < 0.01). Moreover, the longer duration of CO 2 pneumoperitoneum negatively correlated with lower expression of NM23-H1 ( P  < 0.01). In contrast to NM23-H1, MMP-2 expression was significantly higher in CO 2 pneumoperitoneum groups than that in the control group and laparotomy group ( P  < 0.01) and positively correlated with the duration of CO 2 pneumoperitoneum ( P  < 0.01). In addition, there was a negative correlation between the expression of NM23-H1 and MMP-2 ( r  = –0.984, P  < 0.05). Conclusion The CO 2 pneumoperitoneum could promote the proliferation and metastasis of human ovarian cancer in nude mice. This effect was positively correlated with the duration of CO 2 pneumoperitoneum.

Objective Recurrent spontaneous abortion (RSA) is a major pregnancy complication with unclear pathogenesis. This study aims to investigate the role of miR-20b-5p and its downstream target HIF-1[alpha] in trophoblast function and RSA pathogenesis. Methods Placental villous tissues from uRSA patients and healthy pregnant women were collected to assess trophoblast migration, invasion, apoptosis, and placental angiogenesis. The expression levels of miR-20b-5p and HIF-1[alpha] were analyzed using qPCR, Western blot, and immunohistochemistry. HTR-8/SVneo cells were transfected with miR-20b-5p mimics, si-miR-20b-5p, and si-HIF-1[alpha] to evaluate their effects on trophoblast function. Luciferase reporter assays were performed to confirm the regulatory relationship between miR-20b-5p and HIF-1[alpha]. Results Trophoblast cells isolated from uRSA patients exhibited impaired trophoblast invasion and increased trophoblast apoptosis, accompanied by increased trophoblast apoptosis. miR-20b-5p was significantly upregulated, whereas HIF-1[alpha] expression was downregulated in uRSA placental tissues. Overexpression of miR-20b-5p inhibited trophoblast migration, invasion, and endothelial-like differentiation, while its knockdown enhanced these functions. HIF-1[alpha] was identified as a direct target of miR-20b-5p, and its knockdown partially reversed the effects of miR-20b-5p inhibition. Conclusion miR-20b-5p negatively regulates trophoblast function by targeting HIF-1[alpha], contributing to trophoblast dysfunction and RSA pathogenesis. The miR-20b-5p/HIF-1[alpha] axis may serve as a potential therapeutic target for RSA. Keywords: Recurrent spontaneous abortion, Trophoblast, MiR-20b-5p, HIF-1[alpha]

Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/ Gss −/− male mice exhibited normal fertility, due to a compensatory increase in GPX4, which prevented the accumulation of ROS. With aging, there was a decline in GPX4 and an increase in ALOX15 levels observed in 8-month-old S8/ Gss −/− mice, resulting in the accumulation of ROS, lipid peroxidation, and ultimately testicular ferroptosis. We found that testicular ferroptosis did not affect spermatogonia, but caused meiosis disruption and acrosome heterotopia. Then the resulting aberrant sperm showed lower concentration and abnormal morphology, leading to reduced fertility. Furthermore, these injuries could be functionally rescued by inhibiting ferroptosis through intraperitoneal injection of GSH or Fer-1. In summary, Gss in germ cells play a crucial role in the resistance to oxidative stress injury in aged mice. Our findings deepen the understanding of ferroptosis during spermatogenesis and suggest that inhibiting ferroptosis may be a potential strategy for the treatment of male infertility. Facts and questions Conditional deletion of Gss decreases the fertility of 8-month-old male mice Disrupted meiosis and ectopic acrosome are observed in 8-month-old S8/ Gss −/− mice Gss knockout in germ cells causes testis ferroptosis in older mice Both GSH and Fer-1 improve the fertility of 8-month-old S8/ Gss −/− male mice

Background The prevalence of mental disorders is gradually increasing in China. As the Chinese government fully implements the tiered diagnosis and treatment system, community health service centers will take on an increased role in the diagnosis and treatment of mental disorders. However, Chinese general practitioners currently have limited expertise in mental health. The health administration is still exploring which areas should be the focus of training for general practitioners in their capability to handle mental disorders. Objective To understand the types and characteristics of mental disorders, which can provide direction and evidence for improving the diagnosis and treatment capabilities of mental disorders in community mental health services in China. Methods The data of outpatient visits of all community health service centers in Shanghai were extracted from the outpatient and emergency information system platform of primary care institutions during 2014 to 2020. All of the diagnoses of mental disorders were classified and counted according to the ICD-10 code. Mental disorders were analyzed by the specific types, gender, age group and regions. Results From 2014 to 2022, the proportion of patients with mental disorders in community health. Service centers in Shanghai has been increasing year by year, from 0.8% to 2.8%. The most common diagnostic category was F40-48: “Neurotic, stress-related and somatoform disorders”, accounting for 50.9% of all mental disorders. Neurotic disorders, Non-organic sleep disorders and depressive episodes were the top three mental disorders. In the children and adolescents group aged 0–18 years, the most common diagnosis category was F80-F89: “Disorders of psychological development”, accounting for 68.6% of the total number of children and adolescents with mental disorders in community health service centers. In the adult group, the Nonorganic sleep disorders and dementia gradually increased with age, while neurotic disorders and depressive episodes decreased after peaking at age the group 60 to 79. Conclusions In China, an increasing number of patients with mental disorders are seeking medical attention at community health service centers, while the knowledge and skills of general practitioners on mental disorders were still insufficient. Neurotic disorders, insomnia, depression as well as Disorders of psychological development in children and adolescents need to be studied more and paid attention to by general practitioners.

The underlying molecular mechanisms of age-related hearing loss (ARHL) in humans and many strains of mice have not been fully characterized. This common age-related disorder is assumed to be closely associated with oxidative stress. Here, we demonstrate that mTORC1 signaling is highly and specifically activated in the cochlear neurosensory epithelium (NSE) in aging mice, and rapamycin injection prevents ARHL. To further examine the specific role of mTORC1 signaling in ARHL, we generated murine models with NSE-specific deletions of Raptor or Tsc1, regulators of mTORC1 signaling. Raptor-cKO mice developed hearing loss considerably more slowly than WT littermates. Conversely, Tsc1 loss led to the early-onset death of cochlear hair cells and consequently accelerated hearing loss. Tsc1-cKO cochleae showed features of oxidative stress and impaired antioxidant defenses. Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo. In addition, we identified the peroxisome as the initial signaling organelle involved in the regulation of mTORC1 signaling in cochlear hair cells. In summary, our findings identify overactive mTORC1 signaling as one of the critical causes of ARHL and suggest that reduction of mTORC1 activity in cochlear hair cells may be a potential strategy to prevent ARHL.