Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing.

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15-49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02-3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.

Research hotspots and emerging trends in mesenchymal stem/stromal cells in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a prevalent lung disease in neonates that is associated with numerous complications and high mortality. The promising approach to treat BPD is the use of mesenchymal stem cells (MSCs), However, the current treatment of MSCs presents safety concerns, including occlusion of blood vessels and tumorigenicity. In this study, relevant publications from the Web of Science Core Collection were downloaded in January 2023. The acquired data were analyzed and predicted for trends and hotspots in this field using CiteSpace software. Results revealed that in recent years, the focus of co-cited references has been primarily on the clinical studies of MSCs and the application of MSCs derivatives for treating BPD models. The keywords that have gained attention are extracellular vesicles and exosomes. The United States has emerged as the most influential co-authoring country in this field. Among the co-cited journals, the American Journal of Respiratory and Critical Care Medicine holds the highest influence. Thus, this study provides trends in publications, collaboration, research interests, and hotspots, and provides clues for novel ideas and strategies in to further MSCs treatments for BPD.

Transvaginal natural orifice transluminal endoscopic surgery-assisted versus transumbilical laparoendoscopic single-site ovarian cystectomy for ovarian mature cystic teratoma. A randomized controlled trial.

OBJECTIVES: Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and transumbilical laparoendoscopic single-site surgery (LESS) have shown the prospection as minimally invasive procedures. Here we aimed to compare ovarian cystectomy assisted by vNOTES and by LESS for ovarian mature cystic teratoma (OMCT). MATERIAL AND METHODS: A total of 81 premenopausal women with OMCT were randomized to undergo ovarian cystectomy assisted by either vNOTES (n = 41) or LESS (n = 40). The main outcome was the operative time. Secondary outcomes included the length of hospital stay, visual analog scale (VAS) pain scores, abdominal contamination by teratoma contents, and intraoperative and postoperative complications. RESULTS: There were no intergroup differences in age, body mass index, tumor size, or bilaterality of tumor. The operative time for the vNOTES group was significantly shorter than that for the LESS group (68.41 ± 20.92 min vs 85.05 ± 32.94 min, p = 0.008). The highest VAS pain score 24 hours postoperatively was 1.21 ± 0.48 in the vNOTES group and 2.43 ± 0.57 in the LESS group (p < 0.001). Twenty-four of the 40 patients in the LESS group experienced teratoma rupture intraoperatively, leading to abdominal contamination by the teratoma content, while 5 abdominal contamination was observed in the vNOTES group （p = 0.005. No significant differences between the two groups were observed in the other outcomes. CONCLUSIONS: vNOTES assisted ovarian cystectomy has short operative time, fast recovery, no scarring, less pain, and low rate of abdominal contamination. Consequently, vNOTES might be superior to LESS for treating OMCTs.

Highly Regioselective Propargylation/Allenylation of Organolanthanum Reagents with Aldehydes.

The metal-mediated propargylation or allenylation of carbonyl compounds is well-adapted to the preparation of homopropargylic or allenylic alcohols, which are multifunctional intermediates in synthetic chemistry. However, the regioselectivity of reactions using propargyl or allenyl metal reagents is difficult to control, owing to the equilibrium between the two species. In our study, propargyl or allenyl organolanthanum reagents were prepared using trimethylsilylpropyne or prop-1-yn-1-ylbenzene substrates. The treatment of the organolanthanum reagents with aldehydes yielded the regioselective products, respectively. This study provides a better understanding of structural specificity and the special chemoselectivity of rare earth metal reagents.

Effects of Umbilical Preparation Before Trans-umbilical Laparo-endoscopic Single-site Surgery on Umbilical Wounds Healing: a Randomized Controlled Trial.

OBJECTIVE: The umbilicus is the only anatomic entrance and incision site for trans-umbilical laparoendoscopic single-site surgery (TU-LESS). Data on incisional surgical site infections (ISSI) and incision healing in TU-LESS are lacking. Therefore, we aimed to observe umbilical incision healing and possible hernia after TU-LESS and explore the efficacy of preoperative umbilicus preparation on ISSI. SUBJECTS AND METHODS: Consecutive patients aged 18 to 65 years, who were scheduled to undergo TU-LESS at a teaching hospital between March 2020 and November 2021, were enrolled in this prospective study. All patients were randomized to the study group with preoperative umbilicus preparation 30 minutes before patients were sent to the operating room and to the control group without preparation. The umbilical dimple was disinfected twice using povidone-iodine in both groups before the skin incision. The primary outcome was ISSI within 30 days of surgery. Umbilical hernia at 3 months after surgery and perioperative data such as operation time, complications, and incision healing were recorded and compared. RESULTS: A total of 400 patients were recruited for this study. TU-LESS was performed in all patients without major complications. ISSI occurred in 5 patients in the study group (2.5%) and 3 patients in the control group (1.5%), with no significant differences between both groups ( P =0.479). No umbilical hernia occurred in any patient during the 3 months follow-up. Six patients in the study group (3.1%) and 1 in the control group (0.5%) experienced excessive scarring, a relatively high incidence in the study group, though the difference was not statistically significant ( P =0.067). CONCLUSIONS: TU-LESS-related umbilical hernias are rare with existing suturing methods. Umbilicus preparation before TU-LESS could not decrease ISSI; however, it increased the nursing workload, which should be avoided.

Hysteroscopic treatment and reproductive outcomes in cesarean scar pregnancy: experience at a single institution.

OBJECTIVE: To study the risk factors leading to type II/III cesarean scar pregnancy and evaluate the efficacy of hysteroscopic treatment and subsequent reproductive outcomes. DESIGN: Retrospective study from 2013 to 2018. SETTING: Inpatient samples. PATIENT(S): A total of 439 patients with cesarean scar pregnancy received hysteroscopic treatment. They were grouped according to the type of surgery as hysteroscopy combined with dilation and curettage, systemic methotrexate followed by hysteroscopy combined with dilation and curettage, and uterine artery embolization or laparoscopic ligation of bilateral uterine arteries followed by hysteroscopy combined with dilation and curettage. Cesarean scar pregnancy was classified as types I, II, and III on the basis of the relationship between the gestational sac and myometrial thickness by ultrasound. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Risk factors leading to type II/III cesarean scar pregnancy. The success of hysteroscopic treatment as well as favorable reproductive outcomes. RESULT(S): The significant variables were multiple parity, prior cesarean section (CS), hysteroscopic therapy, and dilation and curettage after the last CS between type I and type II/III. There were significant differences among the three groups in symptoms, largest diameter of the gestational sac, presence of fetal heartbeat, myometrial thickness, type of cesarean scar pregnancy, blood loss, length of hospital stay, and expense. The rates of complications and success were 8.2% and 93.6%, respectively. Thirty-seven women conceived again, and 22 women completed a term pregnancy with no uterine rupture. The recurrence rate of cesarean scar pregnancy was 10.8%. CONCLUSIONS: The type of cesarean scar pregnancy is related to the rates of multiple parity, cesarean deliveries, and dilation and curettage procedures after the last CS. Hysteroscopic therapy is a safe and effective surgical approach with a low risk of subsequent ectopic pregnancy.

Highly enantioselective copper-catalyzed propargylic amination to access N-tethered 1,6-enynes.

A highly enantioselective copper-catalyzed propargylic amination starting from benzylic allylic amines has been developed with a new chiral N,N,P ligand. A series of N-tethered 1,6-enynes were synthesized in good to excellent yields with excellent enantioselectivities. Utilization of transition metal-catalyzed cycloisomerization of 1,6-enynes provides several enantioselectively enriched chiral five-membered N-heterocycles efficiently.

The Small-Port Effect and the Small-Triangle Manipulation in Laparoendoscopic Single-Site Surgery: Concept from a Training Model to the Clinic.

Objectives: A small port could possibly minimize the collision of instruments and increase operability in laparoendoscopic single-site surgery (LESS) through the realization of small-triangle manipulation. In this study, we attempted to verify the small-port effect in an in vitro suture model and in vivo LESS hysterectomy with different-sized ports. Subjects and Methods: Two different-sized homemade glove ports were used and assessed in both in vitro and in vivo studies. The trocar head of port 1 was 36 mm in diameter and that of port 2 was 25 mm. Thirty sutures under LESS were conducted in a laparoscopic training box with each port. In LESS hysterectomy, 40 patients were recruited, of whom 20 underwent surgery under port 1 and the remaining 20 under port 2. One surgeon with experience in LESS conducted all sutures. The suture time of each stitch in the training box and for closing the vaginal cuff was videotaped and compared. Results: In the training model, the mean time for each suture with port 1 and port 2 was 18.6 ± 0.5 and 12.5 ± 0.3 seconds, respectively. In LESS hysterectomy, the mean suture time of the vaginal cuff with port 1 and port 2 was 15.2 ± 3.1 and 12.4 ± 2.6 minutes, respectively. Suture with port 2 was less time consuming than that with port 1 in both in vivo and in vitro studies, and the difference was statistically significant. Conclusions: A small port could save time in the suture process both in a training model and in operating room as a result of decrease in instrument collision and realization of small-triangle manipulation.

The different dosages of estrogen affect endometrial fibrosis and receptivity, but not SDF-1/CXCR4 axis in the treatment of intrauterine adhesions.

OBJECTIVE: The study was to evaluate whether fibrotic markers, endometrial receptivity markers and SDF-1/CXCR4 had been changed in the treatment of intrauterine adhesions (IUAs) by different dosages of estrogen. STUDY DESIGN: A total of 39 patients with IUAs were treated with EV 4 mg or 9 mg randomly post-surgery. TGF-ß1/MMP-9, VEGF/αvß3 and SDF-1/CXCR4 were detected in endometrial tissue before and after treatment by real-time PCR and Western blot. RESULTS: TGF-ß1 and MMP-9 expression significantly decreased after treatment for 3 months than before (p < .05), the falling range was larger with EV 4 mg than 9 mg in the mild-moderate degree IUAs (p < .05); Integrin avß3 expression significantly increased after treatment for 3 months than before (p < .05), the variation range was larger with EV 4 mg than 9 mg (p < .05); CXCR4 expression had no significant change after treatment 3 months compared to that before treatment (p > .05). SDF-1 presented an upward tendency at early phase, and it came back to the level of pre-surgery. But there were no significant difference between treatment with 4 mg and 9 mg in the rate of menstrual restoration and pregnancy follow-up 3 months after the treatment. CONCLUSIONS: Endometrium fibrosis may be inhibited and endometrium receptivity may be improved by estrogen with moderate dosage therapy. Compared to the large one, it seems to be advantageous.