Objective To investigate the clinical efficacy of the combined therapy of promoting blood circulation and removing blood stasis and anisodamine hydrobromide in the treatment of sepsis-induced coagulopathy(SIC).Methods A total of 102 SIC patients treated in our hospital from Sep-tember 2021 to September 2024 were selected as study subjects.They were divided into control group(n=51)and experimental group(n=51)according to different treatment methods.The control group received conventional treatment,while the experimental group received an additional combined therapy of promoting blood circulation and removing blood stasis and anisodamine hydrobromide on the basis of the control group.Coagulation function and thrombotic risk were assessed in both groups before treatment and at 24,48,and 72 h after treatment.Clinical efficacy and treatment safety were com-pared,and lactate clearance rate was measured before treatment and at 2,6,and 24 h after treat-ment.Results After treatment,the levels of thrombin time(TT),prothrombin time(PT),acti-vated partial thromboplastin time(APTT),and D-dimer(D-D)decreased,while the platelet(PLT)count and fibrinogen(FIB)levels increased compared with treatment before,with all differ-ences being statistically significant(P＜0.05).At 24 hours post-treatment,the TT,PT,and D-D levels in the experimental group were lower than those in the control group(P＜0.05),whereas no significant differences were observed in the remaining indicators(P＞0.05).At 48 hours post-treat-ment,the TT,PT,APTT,and D-D levels in the experimental group were lower than those in the control group,while the PLT level was higher(P＜0.05).At 72 hours post-treatment,the TT,PT,and APTT levels in the experimental group were lower than those in the control group,whereas the PLT and FIB levels were higher(P＜0.05).The levels of the four new thrombotic indicators,namely thrombomodulin(TM),thrombin-antithrombin complex(TAT),plasmin-α2-antiplasmin complex(PIC),and tissue plasminogen activator-plasminogen activator inhibitor complex(t-PAIC),decreased with prolonged treatment duration in both groups,with differences in different time points being statistically significant(P＜0.05).At 24 hours post-treatment,the TM and TAT levels in the experimental group were lower than those in the control group,with both differences being statistical-ly significant(P＜0.05).At 48 hours post-treatment,the TM,PIC,and t-PAIC levels in the ex-perimental group were lower than those in the control group(P＜0.05).At 72 hours post-treat-ment,the levels of four indicators thrombosis in the experimental group were lower than those in the control group,but only the differences in TM and PIC levels were statistically significant(P＜0.05).The thromboelastography indicators,including R value,K value,and maximum amplitude(MA)decreased,while α angle increased with prolonged treatment duration in both groups(P＜0.05).At 24 and 48 hours post-treatment,the R value in the experimental group was lower than that in the control group,with both differences being statistically significant(P＜0.05).At 72 hours post-treatment,the R value,and MA in the experimental group were lower than those in the control group(P＜0.05).The Sequential Organ Failure Assessment(SOFA)score,SIC score,and Acute Physiology and Chronic Health Evaluation Ⅱ score decreased post-treatment in both groups compared with pretreatment levels,and were lower in the experimental group than in the con-trol group(P＜0.05).The lactate clearance rate increased with prolonged treatment duration in both groups(P＜0.05).At 2,6,and 24 hours post-treatment,the lactate clearance rate in the ex-perimental group was higher than that in the control group(P＜0.05).The 28-day survival rate was 100.00％in the experimental group,which was higher than 92.16％in the control group(P＜0.05).Conclusion The combined therapy of promoting blood circulation and removing blood sta-sis and anisodamine hydrobromide has good clinical efficacy in the treatment of SIC.It can improve patients' coagulation function,reduce thrombotic risk,and has high treatment safety.

Objective:To conduct a comprehensive global review of research on toxic leadership behavior among nursing managers and to analyze the current research status.Methods:Literature related to toxic leadership behavior among nursing managers was retrieved from PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Chinese Science and Technology Journal Database, and China Biomedical Literature Database. The search period extended from the inception of each database to February 15, 2025. The included literature was then organized, analyzed, and summarized.Results:A total of 28 studies were included. There were 23 studies reported the occurrence of toxic leadership behavior among nursing managers, the incidence of toxic leadership behavior was almost at a moderately low level. There were 8 studies reported the influencing factors of toxic leadership behavior, its influencing factors encompassed three primary aspects: the organizational level, the personal characteristics of nursing managers, and characteristics of the nursing staff group. Assessment tools of toxic leadership behavior included the Toxic Leadership Behaviors of Nurse Managers, the Abuse Management Questionnaire, etc. The adverse consequences included increased nurse turnover intention, decreased nursing quality, and reduced organizational trust, etc. Interventions were planned and implemented from three perspectives: the hospital managers, nursing managers, and the nurses.Conclusions:The factors influencing toxic leadership behavior among nursing managers and its adverse consequences require further exploration. Therefore, more intervention studies are warranted to provide new insights and methods for preventing and reducing toxic leadership behavior.

Objective To investigate the expression levels and clinical significance of serum long chain non coding RNA cancer susceptibility candidate 11(lncRNA CASC11)and Testis-associated highly-conserved oncogenic long non-coding RNA(lncRNA THOR)in esophageal cancer patients.Methods Esophageal cancer patients diagnosed in our hospital from January 2017 to January 2021 were selected as the observation group(n=129),and healthy individuals who underwent physical examination in our hospital(n=129)were as the control group.Serum lncRNA CASC11 and lncRNA THOR expression levels were detected by RT-qPCR;the 3-year survival rate was analyzed by Kaplan-Meier method;and the diagnostic value was analyzed by ROC curve.Results The expression levels of serum lncRNA CASC11(1.48±0.35 vs 1.01±0.20)and lncRNA THOR(1.54±0.28 vs 1.11±0.15)in the observation group were obviously higher than those in the control group(P＜0.05).The proportions of high expression of serum lncRNA CASC11 and lncRNA THOR in patients with infiltration depth of T3～T4,tumor diameter＞4 cm,TNM staging of Ⅲ-Ⅳ,and lymph node metastasis were obviously higher than those in patients with infiltration depth T1～T2,tumor diameter ≤ 4 cm,TNM staging Ⅰ-Ⅱ,and no lymph node metastasis(P＜0.05).After 3-year of follow-up,52 out of 129 esophageal cancer patients died and 77 survived.The 3-year survival rate of patients with high expression of lncRNA CASC11(32.20％vs 82.86％)and lncRNA THOR(36.07％vs 80.88％)was obviously lower than that of patients with low expression of lncRNA CASC11 and lncRNA THOR(P＜0.05).The area under the curve(AUC)of serum lncRNA CASC11 and lncRNA THOR levels for diagnosing esophageal cancer was 0.888 and 0.914,respectively,with cutoff value of 1.29 and 1.32.The AUC of the combined diagnosis of the two was 0.946,and the combined diagnosis of the two was superior to their individual diagnosis(Zcombination-lncRNA CASC11=2.410,Zcombination-lncRNA THOR=2.167,P=0.010,0.040).Conclusion The serum levels of lncRNA CASC11 and lncRNA THOR in patients with esophageal cancer are upregulated,they are obviously associated with the 3-year survival rate of patients,and the combination of the two has higher efficacy in the diagnosis of esophageal cancer.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective This study aims to summarize the situation,development experiences,and existing problems in the development of Hospital S,and provide relevant suggestions as a reference for the high-quality development path of public hospitals.Methods Thirteen managers of Hospital S(including hospital leaders,functional departments,and clinical depart-ment heads)and eight experts in the field of hospital management were selected as research subjects.The phenomenological re-search method of qualitative research was used,and semi-structured interviews were conducted to collect relevant data.The Co-laizzi phenomenological data analysis method was used to analyze the interview data.Results Through the analysis of the inter-view data,four themes related to high-quality development were identified:medical care,scientific research and teaching,tal-ents,and disciplines.Each theme has specific areas that need priority and focused attention.Under the theme of medical care,there are four sub-themes:medical quality,medical safety,medical technology,and medical services.Scientific research and teaching,as a strategic support for promoting the hospital's sustained high-quality development,includes four sub-themes:re-search innovation,achievement transformation,teaching system,and mentor team.Talents,as the core competitiveness of the hospital,include three sub-themes:top-level design,high-level talents,and training system.The discipline theme includes four sub-themes:development ideas,development opportunities,development directions,and discipline leaders.Conclusion Public hospitals are facing new situations in high-quality development,and accelerating the improvement of medical service capabilities is a direct manifestation of high-quality development.It is necessary to promote key work such as research innovation,teaching management,talent team building,and discipline construction in a coordinated manner to achieve synchronous improvement in quality and efficiency.

Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T ₁₂ to L ₂, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Humans ; Spinal Cord Stimulation/methods* ; Nerve Fibers/physiology* ; Finite Element Analysis ; Spinal Cord/physiology* ; Computer Simulation ; Spinal Cord Injuries/physiopathology* ; Lumbosacral Region ; Lumbar Vertebrae ; Transcutaneous Electric Nerve Stimulation/methods* ; Models, Neurological

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Objective:To compare changes in retinal and choroidal blood flow in the macular area of eyes with idiopathic macular hole (IMH), fellow eyes, and normal eyes. Additionally, the correlation between these blood flow changes and the occurrence and development of IMH.Methods:A cross-sectional study. From January 2023 to January 2024, 47 patients (47 eyes) diagnosed with IMH (IMH group) in Department of Ophthalmology of The Second Hospital of Hebei Medical University were included in the study. The contralateral eye of IMH eyes was assigned to the contralateral eye group. Healthy volunteers with matched gender and age were selected as the normal control group. Swept-source optical coherence tomography angiography was used to acquire the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the areas within 0-1 mm and 1-6 mm around the fovea, including the superior, temporal, inferior, and nasal regions. Additionally, the choroidal blood flow area (CBFA) and three-dimensional choroidal vascular index (3D-CVI) were measured. The minimum linear diameter (MLD) and base diameter (BD) of the IMH were manually measured. Spearman correlation analysis was performed to evaluate the correlation between the size of the IMH and the various vascular parameters.Results:Compared with the normal control group, the SCP-VD in the 3rd stage ( t=1.298, P=0.009) and 4th stage ( t=1.264, P<0.000) eyes in the IMH group was significantly decreased, with statistical significance; the DCP-VD ( t=1.958, 2.150, 1.712, 1.667; P=0.027, <0.000, <0.000, <0.000) and 3D-CVI ( t=0.027, 0.030, 0.024, 0.023; P=0.005, 0.003,<0.000, <0.000) in eyes of all stages were significantly decreased, with statistical significance; the CBFA in eyes of stages 2-4 was significantly decreased, with statistical significance ( t=0.027, 0.022, 0.021; P=0.028, 0.002, 0.002). Compared with the contralateral eye group, the DCP-VD and 3D-CVI in the IMH group were significantly reduced, with statistical significance ( Z=?3.289, ?2.704; P=0.001, 0.007). Pairwise comparisons between eyes of different stages in the IMH group showed that SCP-VD was significantly different between stage 2 and stage 4 ( t=1.776, P=0.008); DCP-VD was significantly different between stage 1 and stage 3, and stage 1 and stage 4 ( t=1.685, 1.661; P=0.002, 0.000). Correlation analysis showed that SCP-VD was negatively correlated with MLD and BD ( r=?0.508, ?0.408; P=0.002, 0.014); DCP-VD was negatively correlated with BD ( r=?0.410, P=0.013). Compared with the normal control group, the nasal CBFA in stage 3 and 4 IMH eyes ( t=0.149, 0.145; P=0.005, 0.002), and the nasal 3D-CVI in stage 1 and 3 IMH eyes ( t=0.030, 0.027; P=0.002,<0.000) were significantly decreased, with statistical significance. Conclusions:The SCP-VD, DCP-VD, CBFA, and 3D-CVI in IMH eyes were significantly reduced. SCP-VD showed a negative correlation with MLD and BD, while DCP-VD was only negatively correlated with BD.

Objective:To investigate the efficacy of preserving the urethral ridge during Holmium laser enucleation of the prostate（HoLEP）in preventing postoperative retrograde ejaculation and to evaluate its impact on sexual function.Methods:This prospective cohort study enrolled patients with benign prostatic hyperplasia（BPH）who underwent HoLEP at Xiamen Haicang Hospital（Haicang Hospital Affiliated to Xiamen Medical College）from November 2022 to June 2024. Inclusion criteria were as follows：diagnosis of BPH confirmed by color Doppler ultrasound；International Prostate Symptom Score（IPSS）> 7；maximum urinary flow rate（Q max）< 15 ml/s；prostate-specific antigen（PSA）< 4 ng/ml；and an active sexual life with intact antegrade ejaculation. Exclusion criteria included neurogenic bladder，active urinary tract infection（UTI），and other relevant conditions. Patients were grouped based on the operating surgeon's comprehensive judgment during surgery，considering the degree of prostatic median lobe hyperplasia（preserved if hyperplasia was mild，not preserved if severe）. The EP-HoLEP group underwent “tunnel technique” enucleation of the middle lobe hyperplasia with preservation of the urethral ridge，while the HoLEP group underwent conventional prostate enucleation. Primary outcomes included postoperative retrograde ejaculation rate，International Index of Erectile Function（IIEF），Ejaculation Projection Score（EPS），IPSS，Quality of Life Score（QOL），Q max，post-void residual urine volume（PVR），operative time，and postoperative complications. Univariate analysis was used to screen potential influencing factors，followed by multivariate logistic regression to identify independent predictors. Results:Seventy patients with BPH were enrolled，with 35 in each group. Baseline characteristics，including age［（69.97 ± 5.14）years vs.（72.34 ± 5.08）years］，body mass index（BMI）［（22.99 ± 1.41）kg/m2 vs.（23.16 ± 1.38）kg/m2］，prostate volume［47.4（31.9，59.4）ml vs. 44.2（34.9，61.7）ml］，PSA［4.0（1.9，8.2）ng/ml vs. 3.1（2.6，5.0）ng/ml］，hemoglobin［（130.09 ± 12.92）g/L vs.（125.69 ± 17.26）g/L］，IPSS［17（10，22）vs. 17（10，27）］，QOL［5（4，5）vs. 4（4，5）］，Q max［7.5（6.3，9.1）ml/s vs. 7.0（5.9，8.9）ml/s］and PVR［65（22，167）ml vs. 60（16，150）ml］showed no statistically significant differences between the two groups（ P > 0.05）. Operative time［65（55，76）min vs. 63（55，73）min］，postoperative 2-hour hemoglobin［（124.17 ± 14.89）g/L vs.（120.11 ± 15.44）g/L］，and postoperative hospital stay［（3.94 ± 1.89）days vs.（3.66 ± 1.53）days］were also comparable between the two groups（ P > 0.05）. No significant difference was observed in the decrease in IIEF score［1（0，2）vs. 2（0，6）， P = 0.203］. EPS at 3 months［2（1，3）vs. 1（0，2）， P < 0.001］and at 6 months［2（1，2）vs. 1（0，2）， P < 0.001］postoperatively were significantly higher in the EP-HoLEP group. The incidence of postoperative UTI did not differ significantly［5.7%（2/35）vs. 2.9%（1/35）， P = 1.00］. Two cases of urinary retention occurred after catheter removal in the EP-HoLEP group，while none occurred in the HoLEP group. No blood transfusions or urethral strictures were reported in either group. The incidence of retrograde ejaculation was significantly lower in the EP-HoLEP group［28.6%（10/35）vs. 68.6%（24/35）， P <0.001］. Multivariable logistic regression analysis showed that urethral ridge preservation was an independent protective factor for retrograde ejaculation after HoLEP（ OR = 0.159，95% CI 0.053 ? 0.476， P = 0.001）. Conclusions:Urethral ridge preservation during HoLEP is safe and feasible，significantly reduces retrograde ejaculation，and preserves ejaculatory function，though it offers limited erectile function preservation. This approach is suitable for middle-aged，young，or younger elderly patients who prioritize ejaculatory quality，and provides clinical evidence for surgical optimization.

Objective:To investigate the indications for prenatal diagnosis using copy number variation-sequencing (CNV-seq) and the abnormalities detected by the method.Methods:This retrospective analysis involved 17 994 singleton pregnant women who underwent prenatal CNV-seq at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022. These cases were divided into five groups based on the following indications for CNV-seq: abnormal fetal ultrasound findings, high-risk results indicated by non-invasive prenatal testing (NIPT) or Down's syndrome serological screening (Down's screening), adverse pregnancy history, and advanced maternal age. The proportions of cases with the indications for prenatal CNV-seq, the detection rates of abnormalities (numerical abnormalities of chromosomes, pathogenic/likely pathogenic CNV in structural abnormalities) in the five groups, and the distribution of these abnormalities were analyzed. Statistical analysis was performed using Chi-square test. Results:Among the 17 994 pregnant women, the women with abnormal fetal ultrasound findings, high-risk NIPT results, high-risk Down's screening results, adverse pregnancy history, and advanced maternal age accounted for 32.65% (5 875/17 994), 11.90% (2 142/17 994), 31.62% (5 690/17 994), 11.70% (2 105/17 994), and 12.13% (2 182/17 994), respectively. The detection rates of abnormalities in the five groups were 10.60% (623/5 875), 34.64% (742/2 142), 4.69% (267/5 690), 2.99% (63/2 105), and 3.67% (80/2 182), respectively. The overall detection rate of abnormalities was 9.86% (1 775/17 994). The cases with numerical abnormalities of chromosomes accounted for 68.79% (1 221/1 775), trisomy 21 was predominant (49.30%, 602/1 221). Chromosomal structural abnormalities were detected in 31.21% (554/1 775) of the cases with abnormalities, with 57.76% (320/554) harboring pathogenic CNVs and 42.24% (234/554) harboring likely pathogenic CNVs. The detection rate of chromosomal numerical abnormalities was higher than that of structural abnormalities in the abnormal fetal ultrasound group, NIPT high-risk group, and advanced maternal age group [6.81% (400/5 875) vs. 3.80% (223/5 875), χ2=53.10; 27.96% (599/2 142) vs. 6.68% (143/2 142), χ2=338.40; 2.43% (53/2 182) vs. 1.24% (27/2 182), χ2=8.61; all P<0.01]. A total of 416 microdeletions and 255 microduplications were detected in the 554 cases. The top three regions with the highest frequencies in microdeletions were Xp22.31 (12.74%, 53/416), 22q11.21 (7.93%, 33/416), and 17q12 (5.77%, 24/416); in microduplications, they were 22q11.21 (14.90%, 38/255), 17q12 (3.53%, 9/255), and 7q11.23 (3.53%, 9/255). Conclusions:Abnormal fetal ultrasound findings accounted for the highest proportion of prenatal diagnostic indications. The overall detection rate of abnormalities by CNV-seq is relatively high, especially in those with high-risk NIPT results as an indication for prenatal diagnosis. Among the chromosomal structural abnormalities detected in this study, the frequencies of Xp22.31 microdeletion and 22q11.21 microduplication are higher.