Sun-Wei Guo

The phenomenon of neonatal uterine bleeding was observed over centuries. It was dismissed as having no clinical relevance. Alternatively, it was hypothesized to be associated with early-onset endometriosis, but its exact clinical significance remains unknown. We conducted a narrative review using an updated literature of Medline database to July 2026. We examined all identified articles on NUB and examined recent controversies. We explored the relevance of the phenomenon to early-onset endometriosis. We highlight NUB as a putative marker for endometrial maturation and development. The incidence of NUB varies with gestational age. The occurrence of bleeding originating in the uterus of some neonates is well documented. It is possible that some instances of bleeding may not be uterine in origin. The fetal and neonatal endometrium differ significantly from that of the adult. Thus, uterine bleeding in the neonate is not analogous to menstruation. While the factors affecting fetal endometrial development are largely unknown, the occurrence of bleeding in some, but not all, neonates call for a better understanding of the uterine development and the underlying mechanisms of bleeding. The observation that some, but not all, neonates exhibit bleeding may have implications on future uterine development and function. The hypothesis that NUB is associated with early-onset endometriosis, while plausible, has no proven evidence but is difficult to falsify. Whether or not an association exists between NUB and early-onset endometriosis, the phenomenon warrants focus on the physiological stages of early uterine development and maturation and how these may be affected by in utero and early neonatal events.

We have previously reported that induction of adenomyosis in mice results in progressive hyperalgesia, uterine hyperactivity, and elevated plasma corticosterone levels and that epigallocatechin-3-gallate (EGCG) treatment dose dependently suppressed myometrial infiltration and improved generalized hyperalgesia. In this study, we examined whether adenomyosis induced in mice results in the loss of GABAergic inhibition as manifested by the diminished glutamate decarboxylase (GAD) 65-expressing neurons in the brainstem nucleus raphe magnus (NRM) that could correlate with heightened hyperalgesia. We also evaluated whether EGCG treatment would reverse these changes and also improve the expression of some proteins known to be involved in adenomyosis. Adenomyosis was induced in 28 female ICR mice and additional 12 were used as blank controls, as reported previously. At the 16th week, all mice with induced adenomyosis received low- or high-dose EGCG treatment or untreated. Mice without adenomyosis received no treatment. After 3 weeks of treatment, their uterine horns and brains were harvested. The right uterine horn was used for immunohistochemistry analysis and for counting the number of macrophages infiltrating into the ectopic endometrium. The brainstem NRM sections were subjected to immunofluorescence staining for GAD65. We found that mice with induced adenomyosis had significantly diminished GAD65-expressing neurons, concomitant with heightened hyperalgesia. Treatment with EGCG increased these neurons in conjunction with improved hyperalgesia, reduced the expression of p-p65, cycloxygenase 2, oxytocin receptor, collagen I and IV, and transient receptor potential vanilloid type 1 in ectopic endometrium or myometrium, reduced the number of macrophages infiltrating into the ectopic endometrium while elevated the expression of progesterone receptor isoform B. Thus, adenomyosis-induced pain resembles neuropathic pain in that there is a remarkable central plasticity.

In an effort to search for novel therapeutics for adenomyosis, we sought to determine whether treatment with epigallocatechin-3-gallate (EGCG) would suppre

Aim: The aim of this study was to determine the frequency of various symptoms and their associated characteristics in women with adenomyosis who underwent hysterectomy, and to determine which symptoms are likely to go with which others in these patients.Material and Methods: In 2007, 1697 consecutive patients underwent hysterectomy in our hospital. Among them, 734 (43.3%) were histologically confirmed to have adenomyosis, and 710 of them were premenopausal. The medical charts of all 734 patients were retrieved, and their demographic, clinical information and postoperative findings were recorded. We used the Verbal Descriptor Scale to measure the preoperative severity of dysmenorrhea. The Apriori Algorithm was used for mining the association of different symptoms.Results: Among the 710 premenopausal patients, only 4.5% of them had no symptoms. Dysmenorrhea was the most common complaint, occurring in 81.7% of patients. Dysmenorrhea co‐occurred most frequently with menorrhagia. The presence of adhesion, presence of endometriosis, complaint of menorrhagia, longer duration of disease, gravidity, palpable pain during pelvic examination, and diffuse adenomyosis were positively associated with the severity of dysmenorrhea. Age, severity of dysmenorrhea, and complaint of metrorrhagia were positively associated with the risk of menorrhagia.Conclusions: Dysmenorrhea is the most common complaint in women with adenomyosis, which often goes with that of menorrhagia. Adenomyosis often co‐occurs with endometriosis and leiomyomas. Various factors are associated with the risk of having different symptoms.

Following the successful cloning of genes for mostly rare genetic diseases in the early 1990s, there was a nearly universal enthusiasm that similar approaches could be employed to hunt down genes predisposing people to complex diseases. Around 1996, several well-funded international gene-hunting teams, enticed by the low cost of collecting biological samples and China’s enormous population, and ushered in by some well-connected Chinese intermediaries, came to China to hunt down disease susceptibility genes. This alarmed and, in some cases, enraged many poorly funded Chinese scientists, who perceived them as formidable competitors. Some depicted foreign gene-hunters as greedy pilferers of the vast Chinese genetic gold mine, comparing it to the plundering of national treasures from China by invaders in the past, and called upon the government and their fellow countrymen to rise up and protect China’s genetic gold mine. Media uproar ensued, proclaiming the imminent “gene war of the century.” This article chronicles the key events surrounding this “war” and its aftermath, exposes some inherent complexities in identifying susceptibility genes for complex diseases, highlights some issues obscured or completely overlooked in the passionate and patriotic rhetoric, and debunks some misconceptions embedded in this conflict. In addition, it argues that during the entire course of this “war,” the public’s interest went conspicuously unmentioned. Finally, it articulates several lessons that can be learned from this conflict, and outlines challenges facing human genetics researchers.

OBJECTIVE: To estimate patterns of publication of clinical trials of endometriosis registered in ClinicalTrials.gov and their associated characteristics. METHODS: Information on interventional clinical trials on endometriosis that were registered at ClinicalTrials.gov and updated as having been completed by October 25, 2012, was retrieved and the publication status and time to publication in Medline-indexed journals were ascertained by searching PubMed and by sending e-mail inquiries to the principal investigators listed by the registry. RESULTS: Seventy-one interventional trials of endometriosis, testing various drugs and biologicals, were identified. Among them, 49.3% (35/71) were completed by October 25, 2012, 21.1% were either stopped or inactive in the past 2 years, and the remaining 29.6% were ongoing. Among the 35 completed trials, 25 (71.4%) were sponsored by industry and results were published for only 11 (31.4%; five industry-sponsored, and six nonindustry-sponsored). Trials sponsored by industry were nearly four times less likely to publish their results than nonindustry-sponsored trials, even though these trials typically had larger sample sizes and were completed faster. Compared with the publication rate of 20% found 4 years ago, the current rate has increased only marginally but still lies significantly below the reported 66.3% surveyed recently among 546 completed nonendometriosis trials registered at ClinicalTrials.gov (P<.001). CONCLUSION: Despite mounting pressure on more transparency of clinical trials, the current state of transparency or lack thereof of clinical trials on endometriosis is worrisome and does not benefit the trial sponsor or the public. Thus, we again call for more transparency for endometriosis trials. LEVEL OF EVIDENCE: II

We recently reported that Slit/Roundabout (ROBO) 1 pathway may be a constituent biomarker for recurrence of endometriosis, likely through promoting angiogenesis. In this study, we sought to determine as whether Slit2 overexpression can facilitate angiogenesis, increase lesion size, and induce hyperalgesia in mice with induced endometriosis. We used 30 Slit2 transgenic (S) and 29 wild-type (W) mice and cross-transplanted endometrial fragments from S to W (group SW) and vice versa (group WS), and also within the S and W (groups SS and WW, respectively), into the peritoneal cavity, inducing endometriosis. We also performed a sham surgery within both S and W mice (groups Sm and Wm, respectively). The size of the ectopic implants, microvessel density (MVD) and immunoreactivity to ROBO1, and vascular endothelial cell growth factor (VEGF) in ectopic and eutopic endometrium, along with hotplate and tail-flick tests in all mice, were then evaluated. We found that the induction of endometriosis resulted in generalized hyperalgesia, which was unaffected by Slit2 overexpression. Slit2 overexpression did increase the lesion size significantly and correlated positively with the MVD in ectopic and eutopic endometrium. Slit2 expression levels appear to correlate with the MVD, but not with VEGF immunoreactivity, in ectopic endometrium. Consequently, we conclude that Slit2 may play an important role in angiogenesis in endometriosis. The increased angiogenesis, as measured by MVD, but not VEGF immunoreactivity, likely resulted in increased lesion size in induced endometriosis. Thus, SLIT2/ROBO1 pathway may be a potential therapeutic target for treating endometriosis.