Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders.

Different fates of neural stem/progenitor cells (NSPCs) and their progeny are determined by the gene regulatory network, where a chromatin-remodeling complex affects synergy with other regulators. Here, we review recent research progress indicating that the BRG1/BRM-associated factor (BAF) complex plays an important role in NSPCs during neural development and neural developmental disorders. Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation, which can also lead to various diseases in humans. We discussed BAF complex subunits and their main characteristics in NSPCs. With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs, we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs. Considering recent progress in these research areas, we suggest that three approaches should be used in investigations in the near future. Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders. More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.

Three-dimensional imaging analysis for the diagnosis of dural ossification in thoracic ossification of the ligamentum flavum: a multicenter study.

Background: Unforeseen dural ossification (DO) increases the risk of complications in the surgical management of thoracic ossification of the ligamentum flavum (OLF). Several methods have been proposed to identify DO; however, these approaches either have low diagnostic accuracy or poor feasibility. Therefore, we aimed to determine the relationship between DO and the severity and range of thoracic OLF compression using a 3-dimensional (3D) imaging analysis and to evaluate its superiority in diagnosing DO over conventional measurement methods. Methods: A total of 114 consecutive patients who underwent decompressive laminectomy for thoracic OLF in 4 institutions were retrospectively enrolled and divided into DO and non-DO groups. Univariate analysis was performed to determine the relationship between OLF compression and DO. We measured the 3D occupying ratio (OR; 3D OR = OLF volume/normal canal volume × 100%), calculated its cutoff values, and compared its diagnostic value in DO with that of conventional 1D and 2D radiological parameters in the whole thoracic spine. Results: The 3D OR in the DO group (50.9%±7.9%) was significantly higher than that in the non-DO group (30.8%±7.5%; P<0.01). The overall reliability and reproducibility for measurements of the 3D OR (intra- and interobserver correlation coefficients 0.94 and 0.90, respectively) were excellent. Thus, the 3D OR could be used as an indicator to distinguish between DO and non-DO, with high diagnostic accuracy (91.2%). Moreover, a 3D OR of >43%, known as the "ossification zone", was indicative of DO in OLF, whereas a value of <37% was considered the "safe zone". Additionally, the 3D OR [area under the curve (AUC) =0.98, 95% confidence interval (CI): 0.93-0.99] showed a statistically higher diagnostic value for DO in the upper, middle, lower, and whole thoracic spine than did both 1D (AUC =0.81; 95% CI: 0.73-0.88) and 2D (AUC =0.87; 95% CI: 0.79-0.92) parameters (P<0.01). Conclusions: DO was significantly associated with the severity and range of OLF compression. The 3D OR could be used as a critical diagnostic indicator for identifying DO in the whole thoracic spine, owing to its superiority over conventional radiological parameters. Classification of the 3D OR could maximize the clinical feasibility and thus help surgeons to decrease the incidence of DO-related surgical complications.

Anterior controllable antedisplacement and fusion: quantitative analysis of a single surgeon's learning experience.

BACKGROUND CONTEXT: Anterior controllable antedisplacement and fusion (ACAF) is a novel surgical technique for the treatment of ossification of the posterior longitudinal ligament (OPLL) but the surgical learning curve for this technique has not been previously characterized. PURPOSE: The aim of this study was to quantify a surgeon's learning curve for ACAF and the effect of surgeon experience on postoperative outcomes. STUDY DESIGN: Prospective study of a single institution and single surgeon experience with ACAF surgery. PATIENT SAMPLE: A total of 70 consecutive patients with OPLL undergoing ACAF surgery by a single, non-ACAF trained surgeon between 2017 and 2020 were analyzed. OUTCOME MEASURES: Intraoperative and postoperative outcomes (blood loss, operative time, errors of surgical procedure, length of hospital stay, Japanese Orthopedic Association (JOA) scoring system, and surgical complications) were assessed. METHODS: We prospectively reviewed the first 70 ACAF procedures between 2017 and 2020 performed by a single, non-ACAF trained surgeon. The function relationship between the operative time and case number was fitted using a locally weighted scatterplot smoothing (LOESS) plot. Spearman's correlation analysis was performed to determine factors affecting the operative time. The operative time-related learning curve for ACAF was established and difficulty of each procedure was assessed using a cumulative sum (CUSUM) model. The association between the specific errors of surgical procedures and surgeon experience was further analyzed. A modified CUSUM model was also used to establish the surgical procedure-related learning curve, and thus whether these two learning curves matched with each other was observed. Postoperative outcomes in relation to surgeon experience was compared using a Wilcoxon rank sum test and Chi-squared test. RESULTS: Operative time presented a specific pattern of fewer patient-dependent changes as the case number increased. Spearman's correlation analysis showed the operative time was more affected by the case number (r=-0.73) than the complexity of condition and number of levels hoisted. The operative time-related CUSUM model identified the early (first 29 cases) and late phase (late 41 cases) of the learning process, which was also confirmed by a modified CUSUM model based on surgical procedure. The critical point of the CUSUM model for bilateral osteotomies was at case number 29, and time reduction after the early phase was approximately 34 minutes. Length of hospital stay and blood loss were less during the late phase than during the early phase (p<.05). Although no significant difference was observed in postoperative JOA scores between two phases, patients in the late phase obtained higher recovery rates of neurologic function than those in the early phase (p<.01). There was significant difference in the number of specific errors between the two phases (p=.02). There were no significant differences in overall complication rates between two phases, but a higher incidence of certain complications caused by specific errors was observed in the early phase (p=.02), including CSF leakage, C5 palsy and incomplete decompression. CONCLUSIONS: We described, for the first time, a detailed learning curve for ACAF surgery. About 29 cases were needed to achieve mastery of ACAF. Once mastered, the surgeon could deal with various OPLL presentations in a universal way regardless of condition complexity and number of surgical levels. Bilateral osteotomies were the most difficult part of ACAF and produced the greatest reduction in time after mastery. We found a close association between specific errors of surgical procedure for ACAF and surgeon experience. Furthermore, certain complications caused by these errors should be on the alert during the early phase of learning ACAF, including CSF leakage, C5 palsy and incomplete decompression.

Pollen-specific gene SKU5-SIMILAR 13 enhances growth of pollen tubes in the transmitting tract in Arabidopsis.

Pollen tube growth and penetration in female tissues are essential for the transfer of sperm to the embryo sac during plant pollination. Despite its importance during pollination, little is known about the mechanisms that mediate pollen tube growth in female tissues. In this study, we identified an Arabidopsis thaliana pollen/pollen tube-specific gene, SKU5-SIMILAR 13 (SKS13), which was critical for the growth of pollen tubes in the transmitting tract. The SKS13 protein was distributed throughout the cytoplasm and pollen tube walls at the apical region. In comparison with wild-type pollen tubes, those of the sks13 mutants burst more frequently when grown in vitro. Additionally, the growth of sks13 pollen tubes was retarded in the transmitting tract, thereby resulting in decreased male fertility. The accumulation of pectin and cellulose in the cell wall of sks13 pollen tubes was altered, and the content of jasmonic acid (JA) in sks13 pollen was reduced. The pollen tubes treated with an inhibitor of JA biosynthesis grew much more slowly and had an altered distribution of pectin, which is similar to the pollen tube phenotypes of the SKS13 mutation. Our results suggest that SKS13 is essential for pollen tube growth in the transmitting tract by mediating the biosynthesis of JA that modifies the components of pollen tube cell walls.

Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis.

BACKGROUND: Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. METHODS: We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients' history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. RESULTS: Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. CONCLUSIONS: The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

[Rule of acupoint combination in acupuncture treatment of hiccup: a study based on complex network analysis].

OBJECTIVE: To explore the rule of acupoint combination in acupuncture treatment of hiccups. METHODS: Original research articles on acupuncture treatment of hiccup were collected from databases of CNKI, Wanfang, VIP, and Pubmed by using key words of "hiccup", "acupuncture" "diaphragmatic spasm" "body acupuncture" "filiform needle" and "electroacupuncture". According to our inclusive and exclusive criteria, the collected data were extracted to establish an acupuncture prescription database for hiccup. Then, the regularities of acupoint combinations for hiccup were analyzed by using Gephi complex network analysis software. RESULTS: ;A total of 606 articles containing 634 acupoint prescriptions for acupuncture treatment of hiccups were brought into analysis. There were 133 single-acupoint prescriptions (20.98%), which was significantly lower than the multi-acupoint prescription (501, accounting for 79.02%). There were mainly acupoints in multi-acupoint prescriptions, and distal-proximal acupoint combination method were often used as the basis of acupoint selection (326, accounting for 65.07%). A total of 163 acupoints were involved, with a total frequency of 2 969. Among them, Neiguan(PC6) was used most frequently (400 times, accounting for 13.47%), followed by Zusanli (ST36), Zhongwan (CV12), Danzhong (CV17), and Taichong (LR3). The acupoints of the Conceptional Vessel(666 times, accounting for 22.43%), and Stomach Meridian, Pericardium Meridian and Liver Meridian were chiefly used. There were 67 specific acupoints, the frequency of use was 2 555 times(accounting for 86.05% of the total frequency), among which the frequency of the five Shu-points was the highest (875 times, accounting for 29.47% of the total frequency), and followed by eight confluence points. CONCLUSION: ;The core acupoints are PC6, ST36, CV12, etc. and the distal-proximal acupoint combination method found in this study are often used as the basis of acupoint selection and acupoint prescription for acupuncture treatment of hiccup.

Comparison of effectiveness between warm acupuncture with local-distal points combination and local distribution points combination in breast cancer-related lymphedema patients: a study protocol for a multicenter, randomized, controlled clinical trial.

BACKGROUND: Lymphedema is the most common complication after breast cancer treatment, but management of lymphedema remains a clinical challenge. Several studies have reported the beneficial effect of acupuncture for treating breast cancer-related lymphedema (BCRL). Our objective is to verify the effectiveness of warm acupuncture on BCRL and compare the effectiveness of a local distribution acupoint combination with a local-distal acupoint combination for BCRL. METHODS: This is a study protocol for a multicenter, three-arm parallel, assessor blinded, randomized controlled trial. A total of 108 participants diagnosed as BCRL will be randomly allocated in equal proportions to a local distribution acupoint (LA) group, a local-distal acupoint (LDA) group, or a waiting-list (WL) group. The LA and LDA groups will receive 20 acupuncture treatment over 8 weeks with local distribution acupoint combination and local-distal acupoint combination, respectively. The WL group will receive acupuncture treatment after the study is concluded. The primary outcome is the mean change in inter-limb circumference difference from baseline to week 8. The secondary outcomes include volume measurement, skin hardness, common terminology criteria for adverse events 4.03 (edema limbs criteria), stages of lymphedema from the International Society of Lymphology, Disabilities of the Arm, Shoulder and Hand questionnaire, and the Medical Outcome Study 36-item Short-form Health Survey. DISCUSSION: This study aims to provide data on warm acupuncture as an effective treatment for BCRL and at the same time compare the effectiveness of different acupoint combinations. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier NCT03373474 . Registered on 14th December 2017.

Efficacy differences of electroacupuncture with single acupoint or matching acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies have shown that acupuncture is beneficial for the alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack of clinical evidence concerning the effects of acupoint-matching on chemotherapy-induced nausea and vomiting. METHODS/DESIGN: This is a parallel randomized controlled trial to evaluate the occurrence of nausea and vomiting after chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR rating) as the main outcome for cancer. Quality of life, anxiety and depression scores are the secondary outcomes. Quality of life, anxiety and depression scores are the secondary phase. Use of remedy drugs, routine blood examination, and blood biochemical tests are the safety evaluation. We also compare the different effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching groups. DISCUSSION: The results of this trial are expected to explore the effects of matching different acupoints and to offer biologic plausibility for the use of acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV). TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT02195921 , The date of registration was 17 July 2014.

Efficacy and safety of electroacupuncture with different acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. METHODS/DESIGN: This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. DISCUSSION: The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. TRIAL REGISTRATION: The register number of randomized controlled trial is NCT02195908 . The date of registration was 21 July 2014.

Epigallocatechin-3-gallate (EGCG) inhibits 3-hydroxy-3-methylglutaryl-CoA reductase in the presence of glycerol.

The inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) is considered able to decrease serum cholesterol levels and dramatically reduce the risk for cardiovascular and cerebrovascular diseases. The statins, competitive inhibitors of HMGCR, have been employed to control hypercholesterolemia. But their side effects, especially their safety of long-term administration have attracted great attention. Therefore, there is still an urgent requirement for the development of safer inhibitors of HMGCR with less serious side effects. In this study, we cloned and purified the catalytic domain of human HMGCR (△HMGCR), and applied the method of Ultra Performance Liquid Chromatography (UPLC) to assay △HMGCR activity and screen its inhibitors from natural products. The results indicated that EGCG can inhibit △HMGCR in the presence of some glycerol in vitro and can decrease cellular total cholesterol in HepG2 cells. As a consequence, it is promising to put EGCG into the development of hypolipidemic health product.

Fabrication of magnetic-antimicrobial-fluorescent multifunctional hybrid microspheres and their properties.

Novel magnetic-antimicrobial-fluorescent multifunctional hybrid microspheres with well-defined nanostructure were synthesized by the aid of a poly(glycidyl methacrylate) (PGMA) template. The hybrid microspheres were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), X-ray diffraction (XRD) and digital fluorescence microscope. The as-synthesized microspheres PGMA, amino-modified PGMA (NH2-PGMA) and magnetic PGMA (M-PGMA) have a spherical shape with a smooth surface and fine monodispersity. M-PGMA microspheres are super-paramagnetic, and their saturated magnetic field is 4.608 emu·g-1, which made M-PGMA efficiently separable from aqueous solution by an external magnetic field. After poly(haxemethylene guanidine hydrochloride) (PHGH) functionalization, the resultant microspheres exhibit excellent antibacterial performance against both Gram-positive and Gram-negative bacteria. The fluorescence feature originating from the quantum dot CdTe endowed the hybrid microspheres with biological functions, such as targeted localization and biological monitoring functions. Combination of magnetism, antibiosis and fluorescence into one single hybrid microsphere opens up the possibility of the extensive study of multifunctional materials and widens the potential applications.