To study the chemical constituents from the bark of Myrica rubra, fourteen compounds were isolated from the methanolic extract using various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. Their structures were identified on the basis of chemical properties and spectroscopic data, as 3, 5-dimethoxy-4-hydroxymyricanol (1), myricanol (2), myricanone (3), myricanol 11-sulfate (4), myricitrin (5), quercetin (6), quercetin-3-rhamnoside (7), tamarixol (8), uvaol (9), ursolic acid (10), taraxerol (11), myricadiol (12), β-sitosterol (13) and β-daucosterol (14). Among them, compound 1 is a new compound, named as 3, 5-dimethoxy-4-hydroxymyricanol, compounds 8, 9 were isolated from the genus Myrica for the first time.

Objective To investigate the effect of targeted interruption of cyclooxygenase-2 (COX-2) gene by small interference RNA (siRNA) on the expression of COX-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in eutopic and ectopic endometrial stromal cells (ESC) with endometriosis, and the effect on the content of 6-keto-prostaglandin-F1α (6-keto-PGF1α, metabolites of COX) and the apoptosis of eutopic and ectopic ESC with endometriosis. Methods Ectopic and eutopic ESC from 30 women with endometriosis were isolated and cultured respectively. Then, ESC were classified into three groups: interference group, negative control group and blank control group. ESC in interference group were injected into siRNA transfection complex while ESC in negative control group were injected into negative control transfection complex. ESC from 10 participants without endometriosis were the normal control group. The mRNA and protein expression of COX-2, VEGF, MMP-9 in pre-transfected and post-transfected eutopic and ectopic ESC were detected through real time reverse transcription PCR and western blot. The content of 6-keto-PGF1α was determined by ELISA, the apoptotic cells were detected by flow cytometry. Results After interruption of COX-2 gene, there were no significant difference in the mRNA and protein expression of COX-2, VEGF and MMP-9 between the negative control group and blank control group (P>0.05); the mRNA and protein expression of the three genes in interference group were significantly lower than those in negative control group and blank control group (P<0.05); the mRNA expression of the three genes in interference group of eutopic ESC were 0.87±0.06, 1.76±0.59, 1.04±0.32, in interference group of ectopic ESC were 0.75±0.12, 1.62±0.47, 0.88±0.25, the protein expression of the three genes in interference group of eutopic ESC were 0.457 ± 0.019, 0.500 ± 0.012, 0.361 ± 0.008, in interference group of ectopic ESC were 0.323 ± 0.018, 0.474 ± 0.016, 0.339 ± 0.009;the mRNA and protein expression of the three genes in ectopic ESC had a more reduction than those in eutopic ESC (P<0.05). The results from ELISA revealed that the content of 6-keto-PGF1α in the normal control group [(17.7 ± 1.9) pg/ml] were significantly lower than those in the blank control group (P<0.05), the content of 6-keto-PGF1α in ectopic ESC were significantly higher than that in eutopic ESC (P<0.05), the content of 6-keto-PGF1α in the blank control group of eutopic and ectopic ESC were (32.4±2.6) pg/ml, (38.2±3.7) pg/ml;there was no significant difference in the content of 6-keto-PGF1α between the negative control group and blank control group (P>0.05);compared with those of negative control group and blank control group, the content of 6-keto-PGF1αin interference group decreased significantly (P<0.05), the content of 6-keto-PGF1α in interference group of eutopic and ectopic ESC were (17.1 ± 2.4) pg/ml, (20.9 ± 2.7) pg/ml; the content of 6-keto-PGF1α in eutopic ESC had a slightly more reduction than that in ectopic ESC (P>0.05). The results from flow cytometry displayed that, there was no significant difference in apoptotic cells between the negative control group and blank control group (P>0.05);compared with those of negative control group and blank control group, more apoptotic cells were detected in interference group and the difference was significant (P<0.01);the apoptotic cells in ectopic ESC were significantly more than that in eutopic ESC (P<0.05); the apoptosis rate in interference group of eutopic and ectopic ESC were (33.76 ± 0.06)%, (47.18 ± 0.12)%. Conclusions Our results suggested the targeted interruption of COX-2 gene by siRNA effectively inhibited the mRNA and protein expression of COX-2, VEGF and MMP-9 in both eutopic ESC and ectopic ESC with endometriosis, greatly increased the apoptotic rate of cells and obviously reduced the content of 6-keto-PGF1αby inhibiting the activity of COX-2. And the changes in ectopic endometrium were more evident than those in eutopic endometrium.

Objective: To investigate echocardiography characteristics and clinical significance in patients with diastolic mitral regurgitation. Methods: A total of 15 patients with diastolic mitral regurgitation were studied including 1 patient with large volume of aortic regurgitation, 6 with atrial ifbrillation (AF), 2 with atrial lfutter, 1 with II° type I atrio-ventricular block (A-V block), 1 with II° type II A-V block and 4 with III° A-V block. The characteristics of mitral regurgitation were observed, the heart rates, left ventricular size were measured and left ventricular function was detected in all patients. Results: There was 1 large volume aortic regurgitation patient with diastolic mitral regurgitation occurred in slow iflling phase with less volume, it was less than positive velocity; 1 AF patient occurred in mid and late diastolic phase with less volume, it was obviously less than positive velocity; the rest 8 patients all occurred in mid and late diastolic phase, the velocity reached or surpassed to positive velocity. All 15 patients had slow heart rate, increased left heart, decreased left ventricular ejection fraction, tissue Doppler imaging showed that the early diastolic peak slowed down in mitral ring. There were 93% (14/15) patients having obvious systolic regurgitation. Conclusion: The time phase, quantity and velocity of diastolic mitral regurgitation have various characteristics, most of them associated with systolic regurgitation combining abnormal cardiac structure and function. Echocardiography provides important information for clinical treatment.

Objective:To investigate the value of multimodal MRI radiomics in the preoperative prediction of Fuhrman nuclear grade of clear cell renal cell carcinoma (ccRCC).Methods:A total of 129 patients with ccRCC confirmed by pathology from April 2011 to April 2021 in Third Affiliated Hospital of Soochow University were collected, and the imaging and clinicopathological data were retrospectively analyzed. All patients were divided into training set ( n=90) and validation set ( n=39) at the ratio of 7∶3 using random indicator method. According to the postoperative pathological results, Fuhrman grades Ⅰ and Ⅱ were included in the low grade group (96 cases, 65 cases in the training set and 31 cases in the validation set), and Fuhrman grades Ⅲ and Ⅳ were included in the high grade group (33 cases, 25 cases in the training set and 8 cases in the validation set). Two radiologists manually delineated regions of interest (ROI) on T 1WI, T 2WI, Dixon-water, Dixon-fat, susceptibility weighted imaging (SWI), blood oxygen level dependent (BOLD) images, and 396 texture features were extracted from each ROI. In the training set, intra-class correlation coefficient, Mann-Whitney U test, minimum redundancy maximum relevance and least absolute shrinkage and selection operator method were used to reduce the dimension of features to obtain the best texture features. The logistic regression was used to develop the multimodal radiomics model, and the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of the model in identifying high and low-grade ccRCC in training set and validation set. Results:Four SWI, one T 2WI and one BOLD texture features were selected for modeling. The areas under the ROC curve (95%CI) of the multimodal radiomics model for identifying high and low grade ccRCC in the training and validation sets were 0.859 (0.770-0.923) and 0.883 (0.740-0.964), with the specificity at 95.4% and 87.1%, the sensitivity at 68.0% and 87.5%, the accuracy at 87.8% and 87.2%, respectively. Conclusion:The multimodal MRI radiomics model based on T 2WI, SWI and BOLD images has high effectiveness in preoperative predicting Fuhrman nuclear grade of ccRCC.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with dihydrolipoamide dehydrogenase deficiency. METHODS: Potential variants of the DLD gene were detected by whole exome sequencing and verified by Sanger sequencing. RESULTS: Compound heterozygous variants, c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr), were detected in the DLD gene. The c.1058T>C (p.Ile353Thr) variant was derived from his mother and known to be pathogenic. The c.704_705delTT (p.Leu235Argfs*8) variant was derived from his father and was unreported previously. CONCLUSION The compound heterozygous variants of c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr) of the DLD gene probably underlay the disease in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.
Acidosis, Lactic/genetics* ; Dihydrolipoamide Dehydrogenase/genetics* ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Male ; Maple Syrup Urine Disease/genetics* ; Pregnancy ; Whole Exome Sequencing

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD). METHODS: Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing. RESULTS: Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother. CONCLUSION Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.
Adrenal Insufficiency/genetics* ; Child ; Homeodomain Proteins/genetics* ; Humans ; T-Box Domain Proteins/genetics*

OBJECTIVE: To analyze relevant factors for recurrence of ovarian endometriosis after conservative surgery.
 METHODS: A cohort study was performed on 310 patients who had performed conservative surgery for ovarian endometriosis. All patients underwent clinical interview. The relevant factors included: age at surgery, clinical symptom and signs, medical history, gynecologic examination, preoperative gravidity, complication, adenomyosis, American Society for Reproductive Medicine (ASRM) scores, post-operative drug therapy, post-operative gravidity and so on. The logistic regression analysis was performed to determine the predictive factors for recurrence of endometriosis.
 RESULTS: The relevant factors by univariate analysis were determined. The history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, intraoperative ASRM scores, complication of adenomyosis and operation time were the risk factors; whereas pre- and post-operative gravidity, post-operative drug therapy, and age at surgery were the protective factors. Meanwhile, the relevant factors by multivariate analysis were also confirmed. The history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, and intraoperative ASRM scores were the risk factors; whereas post-operative gravidity, post-operative drug therapy, pre-operative gravidity, and age at surgery were the protective factors.
 CONCLUSION The risk factors for recurrence of ovarian endometriosis are history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, intraoperative ASRM scores, whereas the protective factors are pre- and post-operative gravidity, post-operative drug therapy and age at surgery.
Cohort Studies ; Endometriosis ; surgery ; Female ; Humans ; Laparoscopy ; Organ Sparing Treatments ; Ovary ; pathology ; Postoperative Period ; Recurrence ; Risk Factors ; Treatment Outcome

Drug delivery with customized combinations of drugs, controllable drug dosage, and on-demand release kinetics is critical for personalized medicine. In this study, inspired by successive opening of layered structures and compartmentalized structures in plants, we designed a multiple compartmentalized capsular structure for controlled drug delivery. The structure was designed as a series of compartments, defined by the gradient thickness of their external walls and internal divisions. Based on the careful choice and optimization of bioinks composed of gelatin, starch, and alginate, the capsular structures were successfully manufactured by fused deposition modeling three-dimensional (3D) printing. The capsules showed fusion and firm contact between printed layers, forming complete structures without significant defects on the external walls and internal joints. Internal cavities with different volumes were achieved for different drug loading as designed. In vitro swelling demonstrated a successive dissolving and opening of external walls of different capsule compartments, allowing successive drug pulses from the capsules, resulting in the sustained release for about 410 min. The drug release was significantly prolonged compared to a single burst release from a traditional capsular design. The bioinspired design and manufacture of multiple compartmentalized capsules enable customized drug release in a controllable fashion with combinations of different drugs, drug doses, and release kinetics, and have potential for use in personalized medicine.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.