Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary heart disease characterized by bidirectional or polymorphic ventricular tachycardia and an increased risk of sudden cardiac death. Although trans-2,3-enoyl-CoA reductase like (TECRL) is a newly reported pathogenic gene leading to CPVT that can influence intracellular calcium regulation, the unidentified mechanism underlying the pathogenesis of TECRL deficiency-mediated CPVT remains mainly elusive. In the present study, Tecrl knockout (KO) mice were established and the differentially expressed genes (DEGs) were investigated by RNA-sequencing from the heart tissues. In addition, 857 DEGs were identified in Tecrl KO mice. Subsequently, a weighted gene co-expression network analysis was conducted to discern the pivotal pathways implicated in the Tecrl-mediated regulatory network. Moreover, pathway mapping analyses demonstrated that essential metabolism-related pathways were significantly enriched, notably the fatty acid metabolic process and calcium regulation. Collectively, the data suggested a synergistic relationship between Tecrl deficiency and cardiometabolic and calcium regulation during the development of CPVT. Therefore, further studies on the potential function of TECRL in cardiac tissues would be beneficial to elucidate the pathogenesis of CPVT.

Characteristics of vitiligo patients with versus without associated autoimmune thyroid disease.

BACKGROUND: Clinical data are limited in patients with vitiligo with or without autoimmune thyroid disease. OBJECTIVES: The objective of the study was to investigate the clinical features and basic data of patients with vitiligo, especially those with autoimmune thyroid disease. METHODS: The study was a single-center retrospective study. A total of 1305 patients with vitiligo from June 2018 to May 2023 were included, and the clinical characteristics and basic information of the patients were recorded in detail. RESULTS: We identified an association between sex (odds ratio [OR]: 2.380; 95% confidence interval [CI]: 1.772-1.198), vitiligo duration (OR: 1.449; 95% CI: 1.076-1.952), skin involvement exceeding 5% of the body surface area (OR: 3.764; 95% CI: 2.134-6.640), negative emotions (OR: 3.076; 95% CI: 2.292-4.127), vitiligo type (OR: 1.974; 95% CI: 1.096-3.555), family history of AITD (OR: 4.979; 95% CI: 2.687-9.225), and family history of AD (OR: 2.418; 95% CI: 1.410-4.146) and patients with vitiligo. CONCLUSIONS: For patients with statistically significant associated risk factors, differential diagnosis and early intervention should be performed.

The possible impact of the universal two-child policy on pregnancy outcomes.

PURPOSE: The implementation of the universal two-child policy contributes to adverse pregnancy outcomes, but how the policy change leads to adverse pregnancy outcomes is not well elaborated. In this study, we aimed to compare maternal characteristics and complications, accessed the change in the proportion of maternal characteristics and maternal complications, and evaluated the mediation of maternal characteristics on maternal complications. METHODS: Demographic and clinical data of three-level sample facilities were extracted from China's National Maternity Near Miss Obstetrics Surveillance System from Jan 1, 2012 to May 31, 2021. The associations between the universal two-child policy and maternal risk factors, the universal two-child policy and maternal complications, and maternal risk factors and maternal complications were evaluated using multivariate logistic regression analyses, with odds ratios (ORs) and 95% confidence intervals (CIs). Mediation analysis was used to estimate the potential mediation effects on the associations between the policy and maternal complications. Population-attributable fractions (PAF) were conducted to quantify the maternal complications burden attributable to the implementation of the universal two-child policy. RESULTS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facilities. After adjusting for covariables, there were significant associations between the universal two-child policy and maternal risk factors (P < 0.001), the universal two-child policy and an increased risk of maternal complications (P < 0.001), and maternal risk factors and maternal complications(P < 0.001). The effects of the universal two-child policy on maternal near miss and medical disease were significantly mediated by maternal risk factors with mediation proportions of 19.77% and 4.07% at the municipal-level sample facility, and mediation proportions for 2.72% at the county-level sample facility on medical disease. The universal two-child policy contributed 19.34%, 5.82%, 8.29%, and 46.19% in the incidence of the maternal near miss, antepartum or intrapartum complication, post-partum complication, and medical disease at municipal-level sample facility, respectively. The corresponding PAF% at county-level sample facility was 40.49% for maternal near miss, 32.39% for the antepartum or intrapartum complication, 61.44% for post-partum complication, and 77.72% for medical disease. For provincial-level sample facility, the incidence of maternal near miss, antepartum or intrapartum complications, and medical diseases decreased (P < 0.05) and no statistically significant difference occurred in the incidence of post-partum complications. CONCLUSIONS: In the context of the universal two-child policy, the incidence of maternal near miss, antepartum or intrapartum complication, and post-partum complication increased at municipal- and county-level sample facility. Maternal risk factors may play a mediating role in the effect of policy change and maternal complications. Provincial hospitals have been able to improve the quality of perinatal health care and reduce adverse pregnancy outcomes by adjusting their obstetric service strategies in the context of the new birth policy.

Serum Metabolomic Profile in Hypoxia-Induced Pulmonary Hypertension Mice after C75 Treatment.

BACKGROUND: Inhibition of fatty acid synthase (FAS) plays a crucial protective role in pulmonary hypertension (PH). Our aim was to identify novel metabolites in mice with hypoxia-induced PH after treatment with C75 (FAS inhibitor) and to confirm the presence of these metabolites in paediatric patients with PH. METHODS: The PH mouse model was built by chronic hypoxia and ovalbumin (OVA) assistance. Untargeted metabolomics was used to analyse mouse serum. Six children with PH and six relative controls (patients without lung and heart disease) were selected in Shanghai Children's Hospital and they all performed blood tandem mass spectrometry during hospitalization. RESULTS: First, a total of 29 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified as differential metabolites in the hypoxia group compared with the control group. After C75 treatment, symptoms were partially relieved in the PH mouse, and 15 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified in the hypoxia + C75 group compared with the hypoxia group. These differential metabolites were enriched in arginine and glycerolipid metabolism through metabolite set enrichment analyses and were involved in excessive cell proliferation, which was a characteristic of PH. Second, glutamine and caproyl carnitine levels were increased in paediatric patients with PH. CONCLUSIONS: FAS may be a potential PH therapeutic target. Lipid metabolites, polyamine, and glutamine, are closely related to PH. Putrescine and glutamine might be biomarkers for PH.

[Clinical study on the effect of acupuncture on pregnancy outcome in patients with prethrombotic infertility after repeated implantation failure].

OBJECTIVE: To observe the effect of acupuncture combined with medication on the pregnancy outcome of kidney deficiency and blood stasis type recurrent implantation failure (RIF) in prethrombotic infertility patients. METHODS: A total of 70 RIF patients of kidney deficiency and blood stasis type who were to undergo freeze-thaw embryo transplantation were randomly divided into control and treatment groups, with 35 cases in each group. Patients in the control group were given the basic treatment of artificial periodic freeze-thaw embryo transfer and oral aspirin enteric-coated tablet, 25 mg each time, twice a day, for 3 consecutive menstrual cycles. Patients in the treatment group were treated with acupuncture on the basis of the control group, 30 min each time, 3 times a week, for 3 consecutive menstrual cycles. The clinical pregnancy rate, embryo implantation rate and live birth rate of the two groups were compared. Before treatment and 1 day before transplantation, the scores of kidney deficiency and blood stasis symptom were compared. The blood flow pulse index (PI) and resistance index (RI) of the uterus spiral artery were detected by Doppler ultrasound before treatment and 1 day before transplantation. The endometrial thickness was detected 1 day before transplantation. The contents of plasma D-dimer, serum homocysteine (Hcy) and serum thromboxane B2 (TXB2) were detected. RESULTS: The clinical pregnancy rate, embryo implantation rate and live birth rate in the treatment group were higher than those in the control group (P<0.05). After treatment, the scores of kidney deficiency and blood stasis symptom, the levels of plasma D-dimer, serum Hcy and TXB2, the PI and RI value in both groups were decreased (P<0.05) compared with those before treatment, and the indexes in the treatment group were decreased (P<0.05) more than those in the control group. There was no significant difference in endometrial thickness between the two groups. In the course of treatments, 7 patients in the control group underwent gastric distension pain, poor appetite, constipation, nausea and other gastrointestinal reactions, while only 2 patients in the treatment group had the above discomfort reactions. CONCLUSION: On the basis of medication, acupuncture can reduce the serum TXB2 content in RIF patients in prethrombotic state, improve vascular endothelial function, enhance endometrial tolerance, alleviate the symptoms of kidney deficiency and blood stasis, reduce drug adverse reactions, and ultimately improve the pregnancy outcome and increase the rate of embryo implantation.

[Effects of auricular thumbtack needle on lactation function and TDP-43/Btn1A1/XDH pathway in primiparous women with cesarean section].

OBJECTIVE: To observe the effects of auricular thumbtack needle on breast feeding and lactation function in primiparous women with cesarean section, and to explore its mechanism of action from the perspective of lactation-related gene expression. METHODS: One hundred cases of primiparous women with cesarean section were randomly divided into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 2 cases were eliminated). The patients in the control group were treated with routine obstetric care. Based on the treatment of the control group, the patients in the observation group were treated with auricular thumbtack needle at Neifenmi (CO18), Xiong (AH10), Xiongzhui (AH11), Shenmen (TF4), and Jiaogan (AH6a), etc., with one side of auricular point selected, only once for a total of 3 d. The lactation initiation time, lactation adequacy rate at postpartum 72 h, exclusive breastfeeding rate at postpartum 42 d, and breastfeeding score after treatment were compared between the two groups. Real-time quantitative PCR and Western blot method were used to detect the mRNA and protein expression levels of TDP-43, Btn1A1 and XDH. RESULTS: After treatment, the lactation initiation time in the observation group was earlier than that in the control group (P<0.01), and breastfeeding score in the observation group was higher than that in the control group (P<0.01). The lactation adequacy rate at postpartum 72 h was 63.8% (30/47) in the observation group, which was higher than 41.7% (20/48) in the control group (P<0.05). The exclusive breastfeeding rate at postpartum 42 d was 72.3% (34/47) in the observation group, which was higher than 47.9% (23/48) in the control group (P<0.05). The mRNA and protein expression levels of TDP-43 and Btn1A1 in breast milk in the observation group were higher than those in the control group (P<0.01), while there was no statistically significant difference in mRNA and protein expression of XDH in breast milk between the two groups (P>0.05). CONCLUSION: The auricular thumbtack needle in addition to routine care could promote lactation initiation, improve lactation adequacy rate and exclusive breastfeeding rate in primiparous women with cesarean section, and the action mechanism may be related to up-regulation of TDP-43 and Btn1A1 expression.

Whole genome sequencing of multidrug-resistant Proteus mirabilis strain PM1162 recovered from a urinary tract infection in China.

OBJECTIVES: Proteus mirabilis is an important opportunistic Gram-negative pathogen. This study reports the whole genome sequence of multidrug-resistant (MDR) P. mirabilis PM1162 and explores its antibiotic resistance genes (ARGs) and their genetic environments. METHODS: P. mirabilis PM1162 was isolated from a urinary tract infection in China. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed. ARGs, insertion sequence (IS) elements, and prophages were identified using ResFinder, ISfinder, and PHASTER software, respectively. Sequence comparisons and map generation were performed using BLAST and Easyfig, respectively. RESULTS: On its chromosome, P. mirabilis PM1162 harboured 15 ARGs, including cat, tet(J), blaCTX-M-14 (three copies), aph(3')-Ia, qnrB4, blaDHA-1, qacE, sul1, armA, msr(E), mph(E), aadA1, and dfrA1. We focused our analysis on the four related MDR regions: (1) genetic contexts associated with blaCTX-M-14; (2) the prophage containing blaDHA-1, qnrB4, and aph(3')-Ia; (3) genetic environments associated with mph(E), msr(E), armA, sul, and qacE; and (4) the class II integron harbouring dfrA1, sat2, and aadA1. CONCLUSION: This study reported the whole genome sequence of MDR P. mirabilis PM1162 and the genetic context of its ARGs. This comprehensive genomic analysis of MDR P. mirabilis PM1162 provides a deeper understanding of its MDR mechanism and elucidates the horizontal spread of its ARGs, thus providing a basis for the containment and treatment of the bacteria.

In silico characterization of bla NDM-harboring plasmids in Klebsiella pneumoniae.

Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of bla NDM cases occur on plasmids; therefore, we explored the relationships between plasmids and bla NDM genes in K. pneumoniae by analyzing the variants of bla NDM, replicon types, conjugative transfer regions of 171 bla NDM-harboring plasmids from 4,451 K. pneumoniae plasmids. Of the nine identified bla NDM variants, bla NDM-1 (73.68%) and bla NDM-5 (16.37%) were the most dominant. Over half of the bla NDM-harboring plasmids of K. pneumoniae were classified into IncF plasmids. IncX3 single-replicon plasmids (46-57 kb) carried genes encoding relaxases of the MOBP family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 bla NDM-harboring IncN plasmids (38.38-63.05 kb) carrying the NW-type origin of transfer (oriT) regions, genes coding for relaxases of MOBF family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying bla NDM-1 (140.1-329.2 kb), containing the A/C-type oriTs, genes encoding relaxases of MOBH family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The bla NDM-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of bla NDM-harboring plasmids in K. pneumoniae.

In silico characterization of IncX3 plasmids carrying bla OXA-181 in Enterobacterales.

Carbapenem-resistant Enterobacterales poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria via horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing Enterobacterales has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring bla OXA-181 in Enterobacterales is currently scarce. In this study, we aimed to determine the phylogeny and evolution of bla OXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring bla OXA-181 in Enterobacterales, we identified 81 bla OXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored bla OXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of bla OXA-181 among the 66 bla OXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring bla OXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in Escherichia coli and Klebsiella pneumoniae. Most of the IncX3 plasmids harboring bla OXA-181 were human origin. Almost all the bla OXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOBP family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both bla OXA-181 and qnrS1 in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS26 in the same orientation. Our findings provide important insights into the phylogeny and evolution of bla OXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading bla OXA-181 genes in Enterobacterales.

Application of Scanning Magnetic Resonance Imaging in the Diagnosis of Prenatal Placental Implantation and Related Care.

In order to solve the problem of scanning magnetic resonance imaging in prenatal diagnosis, the application and research of placental implantation have been proposed. Placental implantation is a serious obstetric emergency, which refers to the abnormal attachment of placental villi caused by the dysplasia of decidual basal layer. A study from the United States showed that the incidence of placental implantation in pregnant women during delivery increased from 9.9/30000 to 11.6/20000 from 2006 to 2019, which increased the risk of prenatal or postpartum hemorrhage, hysterectomy, stillbirth, abdominal organ injury, and so on. Clinically, patients can show severe prenatal or postpartum hemorrhage, postpartum placental retention, uterine perforation, and secondary infection, which may seriously endanger the lives of pregnant mothers and fetuses. Placental implantation can also have no obvious symptoms before delivery, which leads to insufficient prenatal diagnosis. Gielchinsky retrospectively studied 410 patients with placental implantation and found that only 9 patients were detected by prenatal ultrasound or magnetic resonance imaging (MRI), and the detection rate was only 6.6%. It can be seen that if the accurate diagnosis of placental implantation can be made before prenatal or symptoms appear, clinical intervention treatment can be carried out in time to reduce the probability of hysterectomy and improve the examination means of patients' prerecovery. At present, studies at home and abroad suggest that it has good clinical application value and research prospect in the clinical diagnosis of placental implantation.

Acupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture on female infertility remain controversial. Also, the variation in the participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. The aim of the study is to systematically evaluate the efficacy and safety of acupuncture for female with infertility and hopefully provide reliable guidance for clinicians and patients. METHODS: We searched digital databases for relevant studies, including EMBASE, PubMed, Cochrane Library, and Web of Science, and the Cochrane Library up to April 2021, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF and other treatment. We included studies with intervention groups using acupuncture and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of ten prespecified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. Results: Twenty-seven studies with 7676 participants were included. The results showed that the intervention group contributes more in outcomes including live birth rate (RR = 1.34; 95% CI (1.07, 1.67); P < 0.05), clinical pregnancy rate (RR = 1.43; 95% CI (1.21, 1.69); P < 0.05), biochemical pregnancy rate (RR = 1.42; 95% CI (1.05, 1.91); P < 0.05), ongoing pregnancy rate (RR = 1.25; 95% CI (0.88, 1.79); P < 0.05), adverse events (RR = 1.65; 95% CI (1.15, 2.36); P < 0.05), and implantation rate (MD = 1.19; 95% CI (1.07, 1.33); P < 0.05) when compared with the control group, and the difference is statistically significant. In terms of the number of oocytes retrieved, good-quality embryo rate, miscarriages, and ectopic pregnancy rate, the difference between the acupuncture group and the control group was not statistically significant. Conclusions: Our analysis finds a benefit of acupuncture for outcomes in women with infertility, and the number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings. More double-blind RCTs equipped with high quality and large samples are expected for the improvement of the level of evidence.

[Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status].

OBJECTIVE: To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared. RESULTS: Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (P<0.05), and NO was increased (P<0.05) in the two groups; FPG, 2hPG, FINS and HOMA-IR after treatment were decreased in the IGT group (P<0.05), the improvement of the above indexes in the IGT group was more significant than that in the NGT group (P<0.05). After treatment, the serum levels of ADMD, ET-1 and MDA were decreased (P<0.05), and NO was increased (P<0.05) in the obese subgroup. In the IGT group, the improvement of serum ADMD, ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). In the NGT group, the improvement of ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). CONCLUSION: Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways.

BACKGROUND The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with all reproductive and metabolic phenotypes in a rat model. MATERIAL AND METHODS Twenty-four 3-week-old female Sprague-Dawley rats were randomized into 4 groups: control, Letrozole, HFD, and Letrozol+HFD. The PCOS model was induced by 12 weeks of Letrozole treatment (1 mg/kg p.o. dissolved in 0.5% CMC solutions once daily) and HFD. Ovarian morphology, estrous cyclicity, hormonal status, body weight, glucose and insulin tolerance, lipid profile, and insulin signaling pathway were investigated. RESULTS The rat model manifests anovulatory cycles and PCO morphology, increased body weight, elevated testosterone levels, abnormal glucose and lipid metabolism, and insulin resistance. The rat model also expresses significantly decreased phosphorylation of 6 essential signaling proteins - INSR, IRS, PI3K, AKT, ERK1, ERK2 - in the PI3K/AKT and MAPK/ERK pathways in the classic insulin-sensitive tissues (e.g., quadriceps femoris muscle, omentum majus, and liver), as well as non-classic target ovary tissues. Disrupted insulin signaling contributes to the decrease in insulin sensitivity and compensatory hyperinsulinemia in PCOS rats. CONCLUSIONS Continuous administration of letrozole and high-fat diets can induce PCOS, metabolic phenotypes, and disrupted activation of the insulin signaling pathway.

Novel drug delivery system based on hollow mesoporous magnetic nanoparticles for head and neck cancers--targeted therapy in vitro and in vivo.

Magnetic targeting delivery of anti-cancer drug with controlled drug release function has been recognized as a promising strategy for pursuit of the increased chemotherapeutic efficacy and reduced adverse effects. Superparamagnetic nano-carrier is proved to be an efficient manner for superficial tumor therapy like head and neck cancers. The anti-tumor effect of chemotherapy drug can be enhanced by combining with external magnet. Herein, we reported the fabrication and functionalization of biocompatible and superparamagnetic hollow mesoporous nanoparticles with magnetic targeting. The nanoparticles drug delivery system was constructed by surface-engineering polyacrylic acid (PAA) onto the superparamagnetic nanoparticles which can load bleomycin (BLM) both in the mesoporous structure and via bonding with PAA. The drug was targeted and retained to the focal area under the magnetic field with the nano-carriers, and released sustainably. Detailed investigations demonstrated that PAA-functionalized magnetite nanoparticles loading BLM could stimulate tumor cells to apoptosis locally. The drug loaded and delivery system endowed the anticancer drug with targeting capability in vitro and suppressed the growth of tumor in vivo. The present targeted drug delivery system is a rather simple method without sophisticated chemistry or materials engineering and is promising in contributing to the progress of nanotherapeutics toward efficient head and neck cancer treatment.

[Effect of combined treatment with acupuncture, moxibustion and medication on endometrial receptivity and expression of serum HOXA10 in polycystic ovary syndrome of kidney deficiency and blood stagnation].

OBJECTIVE: To compare the clinical effect of the combined treatment of acupuncture, moxibustion, Chinese herbal medicine and western medication and simple western medication on polycystic ovary syndrome (PCOS) of kidney deficiency and blood stagnation pattern and explore the effect on endometrial receptivity and the expression of serum homeobox gene A10 (HOXA10). METHODS: A total of 60 patients with PCOS of kidney deficiency and blood stagnation pattern were randomized into a combined treatment group and a western medication group, 30 cases in each one. In the western medication group, on the fifth day of menstruation, clomiphene citrate tablets were taken orally, 50 mg each time, once daily, consecutively for 5 days. On the day when the follicle diameter was ≥ 18 mm, chorionic gonadotrophin for muscular injection, a dose of 10 000 U was given. Before sleep, the aspirin enteric-coated tablets were taken orally, 50 mg (except during menstruation). In the combined treatment group, on the base of the treatment as the western medication group, acupuncture and moxibustion were adopted and the Chinese herbal for tonifying the kidney and activating blood circulation was taken orally. The acupoints were Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Zigong (EX-CA 1), etc. Acupuncture was remained for 30 min each time, once every two days and discontinued during menstruation. Chinese herbal was given from the 3rd day of menstruation till the onset of the next menstruation, one dose each day. After consecutive treatment for 3 menstrual cycles in the two groups, the real-time polymerase chain reaction (RT-PCR) method was adopted to determine the expression of serum HOXA10 before and after treatment in the patients of the two groups. The endometrial thickness at ovulatory phase, uterine arterial flow 7 days after ovulation [including uterine arterial pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV)/end diastolic velocity (EDV), meaning S/D], pregnancy rate and the score of Chinese medicine symptoms before and after treatment were compared in the patients between the two groups. RESULTS: ① After treatment, the expression of serum HOXA10 was higher than that before treatment in the patients of the two groups (P<0.01). The increase range in the combined treatment group was larger than the western medication group (P<0.01). ② After treatment, the endometrial thickness at the ovulatory phase was increased in the patients of the two groups (P<0.01). The increase range of the endometrial thickness in the combined treatment group was larger than the western medication group (P<0.01). ③ The pregnancy rate was 46.7% (14/30) in the combined treatment group, higher than 26.7% (8/30) in the western medication group (P<0.05). ④ After treatment, the bilateral uterine arterial PI, RI and S/D values, as well as TCM symptom score were all lower than those before treatment in the patients of the two groups (P<0.01). The decrease range of each index in the combined treatment group was greater than the western medication group (P<0.01, P<0.05). CONCLUSION: The combined treatment with acupuncture, moxibustion and medication effectively improves endometrial receptivity and uterine arterial flow in the patients with PCOS of kidney deficiency and blood stagnation pattern and increases pregnancy rate. The therapeutic effect is better than the simple western medication and its mechanism is probably related to the regulation of serum HOXA10 expression.

Morphologic changes in idiopathic condylar resorption with different degrees of bone loss.

OBJECTIVE: The aim of this case control study was to investigate the sizes, shapes, and articular surface angles of condyles exhibiting idiopathic condylar resorption (ICR) with different degrees of condylar bone loss and to provide additional information for the diagnosis of ICR. STUDY DESIGN: In total, 154 condyles from patients with ICR and 42 healthy condyles were included. The ICR group was further divided into 3 subgroups (ICR I, ICR II, and ICR III) based on the morphology of the condyle. Three-dimensional (3-D) models of the condyles were measured and analyzed by using the Mimics software based on cone beam computed tomography data. RESULTS: The condylar anteroposterior diameter, transverse diameter, height, superficial area, volume, articular surface angles, condylar neck angle, maximal sectional area, and condylar neck sectional area were all significantly different between the ICR group and the control group (P < .05). There were also significant differences among the 3 subgroups in many of these parameters (P < .05). CONCLUSIONS: Morphologic changes in ICR become worse as the disease progresses, with significant differences between diseased and normal condyles. There were many significant differences among the subgroups. Posteriorly inclined condylar neck and slender condylar neck may be associated with ICR.

Metabolomics profiling of cleidocranial dysplasia.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a rare autosomal-dominantly inherited skeletal dysplasia that is predominantly associated with heterozygous mutations of RUNX2. However, no information is available regarding metabolic changes associated with CCD at present. MATERIALS AND METHODS: We analyzed members of a CCD family and checked for mutations in the RUNX2 coding sequence using the nucleotide BLAST program. The 3D protein structure of mutant RUNX2 was predicted by I-TASSER. Finally, we analyzed metabolites extracted from plasma using LC-MS/MS. RESULTS: We identified a novel mutation (c.1061insT) that generates a premature termination in the RUNX2 coding region, which, based on protein structure prediction models, likely alters the protein's function. Interestingly, metabolomics profiling indicated that 30 metabolites belonging to 13 metabolic pathways were significantly changed in the CCD patients compared to normal controls. CONCLUSIONS: The results highlight interesting correlations between a RUNX2 mutation, metabolic changes, and the clinical features in a family with CCD. The results also contribute to our understanding of the pathogenetic processes underlying this rare disorder. CLINICAL RELEVANCE: This study provides the first metabolomics profiling in CCD patients, expands our insights into the pathogenesis of the disorder, may help in diagnostics and its refinements, and may lead to novel therapeutic approaches to CCD.

[Acupuncture and Chinese medicine of artificial cycle therapy for insulin resistance of polycystic ovary syndrome with phlegm damp type and its mechanism].

OBJECTIVE: To explore the effect difference between acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of western medication and simple western medication for polycystic ovarian syndrome (PCOS) of phlegm damp type with insulin resistance, and to explore its mechanism. METHODS: Sixty patients were randomly assigned into an observation group and a control group, 30 cases in each group. Patients of the control group began to take letrozole and metformin orally on the third menstrual day. Patients of the observation group were treated with acupuncture combined with Chinese medicine of artificial cycle therapy on the basis of the treatment of the control group. The main acupoints were Guanyuan (CV 4), Qihai (CV 6) and bilateral Zigong (EX-CA 1), Luanchao (Extra), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6). Dahe (KI 12) was matched in the follicular phase, and warm acupuncture was applied at Guanyuan (CV 4) and Qihai (CV 6); Zhongji (CV 3) and Xuehai (SP 10) were matched in the ovulatory phase, and electroacupuncture were used at Qihai (CV 6) and Zhongji (CV 3), Xuehai (SP 10) and Yinlingquan (SP 9), 2 Hz and continuous wave; The acupoints in the luteal phase were the above main acupoints, at the same time, moxibustion was used at Guanyuan (CV 4) and Qihai (CV 6), the treatment was given once every other day, 30 min a time. There was no treatment in the menstrual phase. Chinese medicine was applied for tonifying kidney and nourishing blood, strengthening spleen and eliminating phlegm. The patients of the two groups were treated for continuous three menstrual cycles. The indexes before and after treatment were detected, including serum microRNA-29 (miR-29) expression, TCM symptom score, insulin (INS), blood-sugar content and homeostasis model assessment-insulin resistance (HOMA-IR) index, the endocrine hormone values of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), LH/FSH ratio, prolactin (PRL). The pregnancy rates of the two groups were compared. RESULTS: After treatment the expressions of miR-29 and TCM symptom scores of the two groups were lower than those before treatment (P<0.01, P<0.05), with better results in the observation group (P<0.01, P<0.05). The levels of LH LH/FSH and T of the observation group were lower than those before treatment (P<0.01, P<0.05), and the T value in the control group decreased after treatment (P<0.05). The changes of LH and LH/FSH in the observation group were better than those in the control group (both P<0.05). After treatment, The INS, blood-sugar content and HOMA-IR were lower than those before treatment in the two groups (P<0.05, P<0.01), with better results for INS and HOMA-IR improvements in the observation group (both P<0.05). The pregnancy rate in the observation group was 56.7% (17/30), which was significantly higher than 30.0% (9/30) in the control group (P<0.05). CONCLUSION: Acupuncture combined with Chinese medicine of artificial cycle therapy can improve the endocrine levels and insulin resistance of PCOS with phlegm damp type. At the same time, the pregnancy rate is improved. By the view of molecular biology, there may be a pathway trough changing serum miR-29 expression.

Comprehensive Analysis of Mandibular Residual Asymmetry after Bilateral Sagittal Split Ramus Osteotomy Correction of Menton Point Deviation.

PURPOSE: Facial asymmetry often persists even after mandibular deviation corrected by the bilateral sagittal split ramus osteotomy (BSSRO) operation, since the reference facial sagittal plane for the asymmetry analysis is usually set up before the mandibular menton (Me) point correction. Our aim is to develop a predictive and quantitative method to assess the true asymmetry of the mandible after a midline correction performed by a virtual BSSRO, and to verify its availability by evaluation of the post-surgical improvement. PATIENTS AND METHODS: A retrospective cohort study was conducted at the Hospital of Stomatology, Sun Yat-sen University (China) of patients with pure hemi-mandibular elongation (HE) from September 2010 through May 2014. Mandibular models were reconstructed from CBCT images of patients with pre-surgical orthodontic treatment. After mandibular de-rotation and midline alignment with virtual BSSRO, the elongation hemi-mandible was virtually mirrored along the facial sagittal plane. The residual asymmetry, defined as the superimposition and boolean operation of the mirrored elongation side on the normal side, was calculated, including the volumetric differences and the length of transversal and vertical asymmetry discrepancy. For more specific evaluation, both sides of the hemi-mandible were divided into the symphysis and parasymphysis (SP), mandibular body (MB), and mandibular angle (MA) regions. Other clinical variables include deviation of Me point, dental midline and molar relationship. The measurement of volumetric discrepancy between the two sides of post-surgical hemi-mandible were also calculated to verify the availability of virtual surgery. Paired t-tests were computed and the P value was set at .05. RESULTS: This study included 45 patients. The volume differences were 407.8±64.8 mm3, 2139.1±72.5 mm3, and 422.5±36.9 mm3; residual average transversal discrepancy, 1.9 mm, 1.0 mm, and 2.2 mm; average vertical discrepancy, 1.1 mm, 2.2 mm, and 2.2 mm (before virtual surgery). The post-surgical volumetric measurement showed no statistical differences between bilateral mandibular regions. CONCLUSIONS: Mandibular asymmetry persists after Me point correction. A 3D quantification of mandibular residual asymmetry after Me point correction and mandible de-rotation with virtual BSSRO sets up a true reference mirror plane for comprehensive asymmetry assessment of bilateral mandibular structure, thereby providing an accurate guidance for orthognathic surgical planning.

A novel three-dimensional smile analysis based on dynamic evaluation of facial curve contour.

The influence of three-dimensional facial contour and dynamic evaluation decoding on factors of smile esthetics is essential for facial beauty improvement. However, the kinematic features of the facial smile contour and the contribution from the soft tissue and underlying skeleton are uncharted. Here, the cheekbone-maxilla contour and nasolabial fold were combined into a "smile contour" delineating the overall facial topography emerges prominently in smiling. We screened out the stable and unstable points on the smile contour using facial motion capture and curve fitting, before analyzing the correlation between soft tissue coordinates and hard tissue counterparts of the screened points. Our finding suggests that the mouth corner region was the most mobile area characterizing smile expression, while the other areas remained relatively stable. Therefore, the perioral area should be evaluated dynamically while the static assessment outcome of other parts of the smile contour contribute partially to their dynamic esthetics. Moreover, different from the end piece, morphologies of the zygomatic area and the superior part of the nasolabial crease were determined largely by the skeleton in rest, implying the latter can be altered by orthopedic or orthodontic correction and the former better improved by cosmetic procedures to improve the beauty of smile.