ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

Objective:To study the role of DDX3X/NF-κB pathway in early neuronal apoptosis in subarachnoid hemorrhage(SAH)mice.Methods:The mouse model of SAH was established by internal carotid artery puncture,and the neurological function score of the mice was evaluated.The DDX3X expression was knocked down using recombinant lentivirus expressing DDX3X targeted shRNA(Lv-shDDX3X),or the NF-κB pathway was inhibited by NF-κB-IN-1(IN-1).Western Blot was used to detect the expression of DDX3X and NF-κB(p65)in mouse cortex.TUNEL/NeuN staining was used to detect the apoptosis of cerebral cortex neurons.Results:Twenty-four hours after SAH operation,the neurological function of mice was significantly impaired(P＜0.05).While the expression of DDX3X was signifi-cantly increased and the expression of NF-κB(p65)was significantly decreased in the cortex(P＜0.05).When the DDX3X expression is knocked down firstly,then SAH surgery is performed.The neurological function of mice was sig-nificantly recovered,and the expression of NF-κB(p65)protein was significantly higher than that in SAH group(P＜0.05);If the NF-κB activity was inhibited by IN-1 while DDX3X knockdown,there is no significant recovery of neuro-logical function in SAH mice.TUNEL/NeuN staining showed that the number of TUNEL-positive neurons in the brain tissue after DDX3X knockdown was less than that in the SAH group(P＜0.05),while the number of TUNEL-positive neurons was not significantly reduced when IN-1 was used to inhibit NF-κB activity at the same time of DDX3X knock-down.Conclusion:DDX3X/NF-κB mediated cell death in mice with early brain injury after SAH.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.

Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

OBJECTIVE: To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated. RESULTS: Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting). CONCLUSION The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.
Humans ; Child ; Female ; Child, Preschool ; Microcephaly/genetics* ; Developmental Disabilities/genetics* ; Intellectual Disability/complications* ; Comparative Genomic Hybridization ; Mutation

Objective To analyze the target volume margins and positioning errors in the radiotherapy for nasopharyngeal carcinoma(NPC)using the cone-beam computed tomography(CBCT)of Halcyon linear accelerator for providing a reference for the margin from clinical target volume to planning target volume(CTV-to-PTV margin)in the radiotherapy for NPC using Halcyon linear accelerator,hence improving treatment precision and effectiveness.Methods A total of 117 NPC patients who received volumetric modulated arc therapy using Halcyon linear accelerator from May 2020 to June 2022 in Jinshazhou Hospital of Guangzhou University of Chinese Medicine were enrolled.The 3861 CBCT images collected from the patients were matched with the CT images to obtain the correction values of the treatment couch in lateral(Lat),longitudinal(Lng)and vertical(Vrt)directions for positioning error analysis.The CTV-to-PTV margin was obtained by the equation(margin =2.5∑+0.7δ).Results The positioning errors in the radiotherapy for NPC using Halcyon linear accelerator were 0.10(0.00,0.10)cm,0.10(0.00,0.20)cm and 0.20(0.10,0.30)cm in Lat,Lng and Vrt directions,respectively.The CTV-to-PTV margins in Lat,Lng and Vrt directions were 0.12,0.12 and 0.09 cm,respectively.Conclusion Low positioning errors can be achieved for NPC patients undergoing image-guided treatment using Halcyon linear accelerator.

Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.

【Objective】 To investigate the expression level of B7-H6 in peripheral blood and bone marrow of patient with chronic myeloid leukemia (CML), and to analyze its association with clinicopathological characteristics and prognosis. 【Methods】 A total of 120 CML patients from January 2010 to May 2013 were selected as study subjects. The expression of B7-H6 mRNA in CML peripheral blood and bone marrow pre- and 3-, 6-, 12-month-posttreatment was detected by quantitative real time PCR, and its correlation between prognosis and clinicopathological factors was analyzed. 【Results】 The expression level of B7-H6 mRNA in the PB, BMMCs of CML patients was lower than that of the normal population (P<0.05). B7-H6 mRNA in PB at 3-, 6-, 12-month-posttreatment increased as compared with that of pre-treatment (P < 0.05). As treatment time prolonged, the expression level of B7-H6 mRNA increased gradually (P < 0.05). B7-H6 levels in BM samples from CML with BCR-ABL1/ABL≤0.1%, CCR were significantly higher than that in patients with BCR-ABL1/ABL>0.1%(P<0.0001) or without CCR (P<0.001). The expression level of B7-H6 in BMMCs was negatively correlated with the BCR-ABL1/ABL level (r=–0.260, P<0.05). Signifiant difference in PFS was observed between patients with high expression level of B7-H6 (not reached, HR: 0.06, 95% CI =0.03-0.37) and low expression level (81 months, HR: 15.58, 95% CI =2.68-30.23) in BM (P<0.05). 【Conclusion】 The low expression of the B7-H6 gene in CML is correlated with BCR-ABL1 copy number and responsiveness to treatment, and monitoring of B7-H6 expression may be used to evaluate CML prognosis, progression and treatment efficacy.

Objective:To investigate the value of α-synuclein (α-syn) concentration in cerebrospinal fluid (CSF) in predicting postoperative delirium (POD).Methods:One thousand patients underwent elective surgery with combined epidural-spinal anesthesia in our hospital from January 2018 to September 2020 were selected.The epidural puncture was performed at L 3, 4 interspace, and 2 ml of CSF was collected after the needle reaching the subarachnoid space.The concentrations of α-syn, β-amyloid (Aβ)40, Aβ42, total tau protein (T-tau), and phosphorylated tau protein (P-tau) in CSF were determined by enzyme-linked immunosorbent assay.The concentrations of α-syn in CSF and occurrence of POD in patients of different ages were recorded.Patients were divided into POD group and non-POD group according to whether POD occurred, and frequency matching (1∶1) was performed based on five matching variables of age, ASA physical status, education level, duration of operation, and intraoperative blood loss. Results:Eight hundred and forty-one patients were finally included in the study, and the incidence of POD was 15.0%. There were 126 cases in POD group and 126 cases in non-POD group after matching. The concentrations of α-syn in CSF and incidence of POD were gradually increased with age ( P<0.05). Compared with non-POD group, the concentrations of α-syn, T-tau and P-tau in CSF were significantly increased, the concentrations of Aβ40 and Aβ42 were decreased, Aβ40/P-tau, Aβ42/P-tau, Aβ42/Aβ40 and P-tau/T-tau were decreased in POD group ( P<0.05). After confounding factors were corrected by logistic regression analysis, increased concentrations of α-syn, p-tau, and T-tau in CSF were risk factors for POD ( P<0.05). Increased concentrations of Aβ40 and Aβ42 in CSF and increased Aβ40/P-tau and Aβ42/P-tau were protective factors for POD ( P<0.05). Multiple linear regression analysis showed that the concentration of α-syn in CSF was negatively correlated with Aβ40 and Aβ42 concentrations and positively correlated with P-tau and T-tau concentrations ( P<0.05). The area under the receiver operating characteristic curve of concentrations of α-syn in CSF predicting POD was 0.895, Youden index was 0.664, sensitivity was 80.00%, and specificity was 86.36% ( P<0.001). Conclusion:The concentration of α-syn in CSF is related to the occurrence of POD, and it provides higher accuracy in predicting POD.