dThe emergence of ceftriaxone-resistant Neisseria gonorrhoeae is currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance in Neisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation in penA (A501V). However, differential analysis of the genomes and transcriptomes between pre-and postselection strains revealed many other mutated genes as well as up-and downregulated genes. Transformation of the mutated penA gene into nonresistant strains increased the MIC between 2.0-and 5.3-fold, and transformation of mutated ftsX increased the MIC between 3.3-and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, while pilM, pilN, and pilQ were downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance of Neisseria gonorrhoeae to ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry. Gonorrhea is one of the most prevalent sexually transmitted infections (STIs), and it is associated with many severe clinical symptoms such as prostatitis, seminal vesiculitis, pelvic inflammation, infertility, and ophthalmia neonatorum (1). Although epidemiological data show a decreased trend in gonorrhea incidence as a whole, in some countries, the incidence is increasing, especially in specific population groups (adolescents, men who have sex with men, or sex workers) or specific venues (brothels) (2-5). The pathogen responsible for this disease is Neisseria gonorrhoeae. According to worldwide surveillance reports, N. gonorrhoeae has developed resistance to several kinds of antibiotics over the past decades (6-10). Of increasing concern is the prevalence of ceftriaxone (CRO)-resistant N. gonorrhoeae (11), because CRO is the first-line empirical drug for gonorrhea treatment in dual therapy with azithromycin or doxycycline recommended by the WHO (covering the Western Pacific region and the Southeast Asian region) and the CDC (12-14). Several CRO-resistant gonococcal strains, such as H041 and F89, were isolated recently from patients who had a treatment failure with CRO (H041) and cefixime (F89) (15-18). Highlighting the seriousness of these resistant strains, Ohnishi et al. proposed the concept of an N. gonorrhoeae "superbug" in 2011 (17). Uncovering the mechanisms of CRO resistance is now a critical topic of N. gonorrhoeae research.Previous s...

Although reminiscence therapy alleviates mental illness and improves quality of life in neurocognitive disorders patients, little study reports its clinical application in cancer patients. Thus, this study aimed to explore the effect of reminiscence therapy on anxiety, depression, quality of life, and survival profile in postoperative gastric cancer patients. One hundred sixty surgical gastric cancer patients were enrolled in this randomized, controlled study, then randomly assigned to Reminiscence therapy group (N = 80) and Control group (N = 80) as 1:1 ratio. The evaluation was carried at baseline (M0), month 3 (M3), month 6 (M6), month 9 (M9), and month 12 (M12) after intervention by Hospital Anxiety and Depression Scale and European Organization for Research and Treatment of Cancer quality of life Questionnaire-Core 30 (QLQ-C30). Furthermore, disease-free survival and overall survival were analyzed using follow-up data. Reminiscence therapy decreased HADS for anxiety score at M6, M9, and M12, decreased anxiety rate at M9 and M12 compared to control care; while it did not affect HADS for depression score or depression rate at any time-point. Also, reminiscence therapy raised QLQ-C30 global health status score at M12, reduced QLQ-C30 symptoms score at M6, while did not affect QLQ-C30 function score at any time-point compared to control care. Reminiscence therapy did not affect disease-free survival and overall survival, either. Further subgroup analyses (divided by age and gender) observed that the effect of reminiscence therapy seemed more obvious in patients with age ≤60 years and male patients. Reminiscence therapy exhibits alleviation of anxiety and improvement of quality of life in postoperative gastric cancer patients.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. Cryptotanshinone (CRY) has been shown to be effective in reversing reproductive disorders, but whether it can be used in the treatment of polycystic ovary syndrome remains unclear. We aimed to explore whether the mechanism of cryptotanshinone (CRY) in the treatment of polycystic ovary syndrome (PCOS) can be driven via regulating ferroptosis. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. An in vitro model of ischemia-reperfusion (IR) of granulosa cells was established. The in vitro and rat models of PCOS were subjected to different treatments including ferroptosis activators and inhibitors, CRY, and MAPK inhibitor. Oxidative stress was evaluated by measuring the activities of SOD, MDA, and GSH-PX. Total body weight and ovarian weight, as well as the levels of LH and the LH to FSH ratio, significantly increased in rats with PCOS, compared with controls. The expression of Bax was increased in PCOS tissues while PGC1α, NFR1, GPX4, catalase p-ERK, and Bcl-2 were all downregulated. Ferroptosis activator, erastin, had effects similar to those of PCOS while the contrary was found with CRY and ferroptosis inhibitor treatment groups. In vitro, CRY inhibited oxidative stress, MMP, and NF-κB and activated MAPK/ERK signaling by regulating ferroptosis. Overall, this study indicated that CRY protects against PCOS-induced damage of the ovarian tissue, via regulating oxidative stress, MMP, inflammation, and apoptosis via regulating ferroptosis.

No abstract