Qiyu Yang

The morphological appearance of zona pellucida (ZP) is considered to be predictive of the quality of the oocytes and embryos. Agar-like ZP represents a com

Background: The quality of in vitro matured (IVM) oocytes remains inferior to that of in vivo matured oocytes, likely due to DNA damage induced by the in vitro environment. Although rapamycin has been shown to improve the developmental competence of IVM oocytes by reducing DNA double-strand breaks (DSBs), the underlying mechanisms remain unclear. Methods: Immature oocytes from 6 ~ 8-week-old ICR female mice were subjected to IVM with or without rapamycin. After 14 ~ 16 h, the maturation rate, DNA DSB levels, and subsequent developmental competence of IVM oocytes were assessed. The homologous recombination (HR) and non-homologous end joining (NHEJ) pathways were selectively inhibited using RAD51 and DNA-PK inhibitors, respectively, to elucidate the predominant DNA damage repair pathway during IVM and investigate the effects of rapamycin on this process. Results: Embryos derived from the rapamycin-treated group exhibited significantly higher 2PN and cleavage rates compared to the control group. MII oocytes cultured with rapamycin showed reduced γH2AX immunofluorescence intensity, indicating lower DNA damage levels. Additionally, the expression levels of RAD51 and DNAPK were elevated in rapamycin-treated oocytes. Inhibition of RAD51 significantly reduced the maturation rate and increased DNA damage levels, whereas DNAPK inhibition had no effect on oocyte development or quality. Importantly, the beneficial effects of rapamycin on IVM oocytes were diminished under RAD51 inhibition. Conclusion: Rapamycin improves the developmental competence of IVM oocytes by enhancing the RAD51-mediated HR pathway, thereby enhancing DNA stability.

Using 70 U/ml or 35 U/ml as CA125 routine abnormal threshold may result in omissions in the relapse detection of Ovarian cancer (OvCa). This study aimed to clarify the association between a biochemical relapse (only the elevation of CA125) and an image-identified relapse to predict the relapsed lesions better. 162 patients who achieved complete clinical response were enrolled from women diagnosed with stage I-IV serous ovarian, tubal, and peritoneal cancers from January 2013 to June 2019 at our center. The CA125 level of 2 × nadir was defined as the indicator of image-identified relapse (P < 0.001). Compared to CA125 level exceeding 35 U/ml, the 2 × nadir of CA125 improve the sensitivity of image-identified relapse (84.9% vs 67.4%, P < 0.001); the 2 × nadir value can act as an earlier warning relapse signal with a longer median time to image-identified relapse (2.7 vs. 0 months, P < 0.001). Of the relapsed population, there was no difference of CA125 changing trend between the neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) group after initial treatment. Compared with 35 U/ml, CA125 reaching 2 × nadir during the follow-up process might be a more sensitive and early relapse signal in patients with serous OvCa. This criterion may help guide patients to be recommended for imaging examination to detect potential relapse in time.

Background: In mammals, normal fertilization depends on the structural and functional integrity of the zona pellucida (ZP), which is an extracellular matrix surrounding oocytes. Mutations in ZP may affect oogenesis, fertilization and early embryonic development, which may cause female infertility. Methods: A PubMed literature search using the keywords ‘zona pellucida’, ‘mutation’ and ‘variant’ limited to humans was performed, with the last research on June 30, 2022. The mutation types, clinical phenotypes and pregnancy outcomes were summarized and analyzed. The naive Bayes classifier was used to predict clinical pregnancy outcomes for patients with ZP mutations. Results: A total of 29 publications were included in the final analysis. Sixty-nine mutations of the ZP genes were reported in 87 patients with different clinical phenotypes, including empty follicle syndrome (EFS), ZP-free oocytes (ZFO), ZP-thin oocytes (ZTO), degenerated and immature oocytes. The phenotypes of patients were influenced by the types and location of the mutations. The most common effects of ZP mutations are protein truncation and dysfunction. Three patients with ZP1 mutations, two with ZP2 mutations, and three with ZP4 mutations had successful pregnancies through Intracytoplasmic sperm injection (ICSI) from ZFO or ZTO. A prediction model of pregnancy outcome in patients with ZP mutation was constructed to assess the chance of pregnancy with the area under the curve (AUC) of 0.898. The normalized confusion matrix showed the true positive rate was 1.00 and the true negative rate was 0.38. Conclusion: Phenotypes in patients with ZP mutations might be associated with mutation sites or the degree of protein dysfunction. Successful pregnancy outcomes could be achieved in some patients with identified ZP mutations. Clinical pregnancy prediction model based on ZP mutations and clinical characteristics will be helpful to precisely evaluate pregnancy chance and provide references and guidance for the clinical treatment of relevant patients.

Wang M, et al. World J Mens Health. 2022 Oct;40(4):570-579. https://doi.org/10.5534/wjmh.220017

Pelvic exenteration (PE) refers to the en bloc resection of the involved pelvic organs along with pelvic reconstruction so as to enhance the survival rate for tumor patients. First reported by Brunschwig in 1948,[1] PE has thereafter been utilized to treat rectal cancer, bladder cancer, prostate cancer, and cervical cancer as a curative or palliative treatment for advanced or recurrent malignancies. It is critical to carry out surgical resection of all the involved tumor lesions so as to prolong the overall survival (OS) of patients; nonetheless, such medical manipulation will induce various complications. For patients undergoing radiotherapy in the initial treatment, the increased tissue fragility, together with inflammation, has become trouble intraoperatively.[2] Robot-assisted laparoscopic surgery is developed on the basis of traditional laparoscopy, which has completely inherited the superiorities of laparoscopic surgery. More importantly, it can achieve a more stereoscopic visual field as well as more precise operation through establishing the three-dimensional visual field, and using the inner wrist system as well as the tremor filtering system. Moreover, it can accurately return to the last operation area through the presetting and memory function of its system software, which can, thus, contribute to avoid miscarriage, further reduce intraoperative blood loss, and decrease the occurrence of intraoperative complications.[3,4] In 2009, Lim et al[5] had first performed the robot-assisted laparoscopic PE (RALPE) combined with ileal loop urinary diversion for a relapsed cervical cancer patient. The operation time was 375 min, the blood loss was about 375 mL, and no intra- or post-operative complications were observed. Thereafter, surgical teams from countries all over the world have continuously applied RALPE in treating gynecologic malignancies. This study aimed to review the application of RALPE in treating gynecologic malignancies, including its indications, methods and feasibility, complications, and follow-up. Gynecologic malignancies have not only posed a severe threat to women's lives, but also caused various complications due to the invasion to surrounding tissues and organs, thus seriously affecting the quality of life of these patients. Surgery is not recommended in the guidelines to be the preferred choice for advanced cancer; in addition, surgical treatment has been generally recognized to be of limited value for patients developing distant metastasis.[6] As a result, physicians should carefully and strictly select the appropriate patients so as to ensure the safety and effectiveness of surgery. Specifically, factors including previous treatment history, size of recurrent tumors, distant metastasis, negative margin, the general condition of patients, economic conditions, and treatment intention should be evaluated preoperatively. Over the last decades, the indication for PE has evolved from the classical indication of centrally persistent or recurrent cervical cancer to the locally advanced primary cancers or the recurrent endometrial, vulvar, vaginal, and ovarian cancers in selected cases; notably, pelvic sidewall recurrence is no longer an absolute contraindication.[2,7,8] In a recent monocentric cohort study carried out by Knight et al,[9] the frequency of PE performed during four successive periods had been evaluated, and it was concluded that the indications for PE had evolved toward the curative intents, though PE was initially developed to manage palliative situations with severe pelvic symptoms (such as fistulas, bleeding, visceral, and parietal pain) with no other therapeutic options. Typically, the increased success rate of curative PE can be attributed to the better selection of patients. However, it remains controversial regarding the importance of nodal involvement, though some studies have associated it with poor patient prognosis.[10,11] Meanwhile, some other studies do not identify that pelvic lymph or para-aortic lymph node metastasis and/or hydroureteronephrosis is a contraindication.

Rationale:Pelvic exenteration is considered a method to treat central recurrent or persistent gynecologic malignancy after the initial therapy. The postoperative survival rate has been greatly increased by the improvement in the surgical technology and the perioperative management. Yet various complications are still impacting the quality of life. New technologies such as robotic surgery system made it possible to approach radical surgical resection by using a minimally invasive method.Patient concerns:The patient is a 53-year-old female with the cervical adenocarcinoma pelvic recurrence who had undergone the adjuvant chemo-radiotherapy and the laparoscopic radical hysterectomy in our hospital 2 years ago. She still expected her life to be prolonged through surgery therapy.Diagnoses:Locoregional recurrence of cervical adenocarcinoma.Interventions:A robotic total pelvic exenteration with ileal neobladder was performed.Outcomes:The postoperative results were excellent and after 17-month follow-up, the patient is alive and satisfied without any recurrence or distant metastasis.Lessons:For the patients with advanced or recurrent cervical cancer who are willing to receive surgical therapy and not sensitive to chemo-radiotherapy, robotic-assisted laparoscopic total pelvic exenteration is technically a feasible surgical method for recurrent pelvic malignancies. Yet the operation time should be further controlled to reduce complications which include pressure sore and thrombus. Moreover, appropriate assessment is required in the selection of the methods for reconstruction.

The purpose of this paper was to study the effect of different parameters of high frequency nanosecond pulse bursts on the rabbit muscle contraction strength. Ten unipolar high frequency pulse bursts with different field intensities (1 kV/cm, 4 kV/cm and 8 kV/cm), intra-burst frequencies (10 kHz, 100 kHz and 1 MHz) and intra-burst pulse numbers (1, 10 and 100) were applied through a pair of plate electrode to the surface skin of the rabbit's biceps femoris, and the acceleration signal of muscle contraction near the electrode was measured with a three axis acceleration sensor. The time and frequency domain characteristics of the acceleration signals were analyzed. The animals show dose-dependent increase in the amplitude of the acceleration signal of the muscle contraction. However, the spectral distributions of the signals are similar under different pulse bursts. Further analysis of the experimental results illustrates when the intra-burst frequency is relatively low, appropriate increase in the intra-burst pulse numbers will not increase muscle contraction strength significantly; however when the intra-burst frequency is relatively high, the intra-burst pulse numbers should be minimized as far as possible. This will provide reference for the selection of parameters in the actual tumor treatment performed with high frequency nanosecond pulses in the future.