Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy / 中华医学杂志(英文版)

BACKGROUND@#Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients.@*METHODS@#The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.@*RESULTS@#A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram.@*CONCLUSIONS@#We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

Regulation of Yes associated protein in diabetic nephropathy mice by Yishen Huashi Granule / 中国药理学通报

Aim To explore the protective effect of Yishen Huashi Granule (YSHS) on streptozotocin (STZ) - indueed diabetes nephropathy (DN) in mice and its possible mechanism. Methods The STZ induced DN mice model was established, which was randomly divided into model group, YSHS group and YAP inhibitor Vertepofin group, and the eontrol group was also established. The intervention was started eight weeks after the successful modeling with the course of four weeks. Urine protein concentration before and after intervention in each group as well as serum creatinine (Scr) and blood urea nitrogen (Bun) levels after intervention were measured. After the treatment, the mice were sacrificed, and the pathological changes of glomeruli were observed by light microscope HE staining. The protein expression of YAP, p-YAP S127 and CTGF were detected by Western blot, and the mRNA expressions of YAP, CTGF and podocyte functional proteins nephrin, podophyxin and WT1 were detected by RT-PCR. Results The biochemical indexes of YSHS group were better than those of model group, and HE staining showed that the pathological injury of glomeruli was improved. In the model group the protein expression of YAP, p-YAP (S127) and CTGF as well as the mRNA expression of YAP and CTGF increased, while the mRNA expression of nephrin, podocalyxin and WT1 decreased. After YSHS treatment, the protein expression of YAP, p-YAP S127, CTGF and the mRNA expression of YAP and CTGF decreased, while the mRNA expression of nephrin, podocalyxin and WT1 increased. Conclusions YSHS can reduce urinary protein, protect renal function and alleviate glomerular pathological injury in DN mice. Its possible mechanism may be related to the down-regulation of YAP in renal tissue, the reduction of CTGF expression level and the up-regulation of podocyte protein mRNA expression.

A case report of SARS-CoV-2 encephalitis / 上海预防医学

A patient with SARS-CoV-2 infection was adimitted to Shanghai Shibei hospital of Jing'an District in early 2023. According to the patient's complaits， clinical manifestations， physical symptoms， laboratory examination， radiological image results， plus lumbar puncture， the patient was diagnosed with novel coronavirus encephalitis. The patient was discharged from the hospital after a combined treatment of Chinese and western medicine.

Short-term outcomes and long-term quality of life after undergoing radical proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis for Siewert type II and III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis / 中华胃肠外科杂志

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ2=8.711, P=0.003 and χ2=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ2=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ2=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.

Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

MiR-744-5p inhibits the proliferation, invasion, and migration of clear-cell renal cell carcinoma cells by targeting CCND1 / 南方医科大学学报

OBJECTIVE@#To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC).@*METHODS@#We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments.@*RESULTS@#MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05).@*CONCLUSION@#MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.

Clinical observation on plastic splint treatment of middle clavicle fracture based on a new classification / 中国骨伤

OBJECTIVE@#According to 73 patients with middle clavicle fracture treated conservatively, a new classification of middle clavicle fracture was proposed, and the clinical effect of plastic splint in the treatment of middle clavicle fracture was observed.@*METHODS@#Total 73 patients with middle clavicle fracture treated with plastic splint from September 2018 to August 2020 were analyzed retrospectively. All the patients were divided into 4 types according to the degree of fracture displacement. There were 16 cases of typeⅠ, including 7 males and 9 females, ranging in age from 18 to 37 years old, with a mean of (28.6±7.8) years old;12 cases of mild disease, 3 cases of moderate disease and 1 case of severe disease. There were 16 cases of type Ⅱ, including 6 males and 10 females, ranging in age from 25 to 49 years old, with a mean of (37.3±9.4) years old;5 cases of mild disease, 8 cases of moderate disease and 3 cases of severe disease. There were 7 cases of type Ⅲ, including 4 males and 3 females, ranging in age from 33 to 57 years old;2 cases of mild disease, 3 cases of moderate disease and 2 cases of severe disease. There were 34 cases of type Ⅳ, including 16 males and 18 females, ranging in age from 48 to 82 years old, with a mean of(66.4±14.9) years old;7 cases of mild disease, 17 cases of moderate disease and 10 cases of severe disease. All patients received plastic splint external fixation for 4 weeks. Visual analgue scale (VAS) and Constant-Murley shoulder scores before treatment and 1, 3 and 9 months after treatment were observed and recorded to evaluate the change of pain degree and shoulder function recovery before and after treatment. The patients' satisfaction with the appearance after treatment was recorded at the latest follow-up. The X-ray findings at the latest follow-up were used to judge whether the patient had fracture nonunion. And according to the fracture healing time and imaging findings, the excellent and good rate of clinical curative effect in patients with different types was obtained.@*RESULTS@#All patients were followed up, and the duration ranged from 9 to 11 months, with a mean of (9.8±0.7) months. The VAS scores of typeⅠ, typeⅡand type Ⅳ before treatment were 2.88±0.83, 3.67±0.80 and 6.92±1.71 respectively, which were decreased to 0.54±0.19, 0.77±0.25 and 1.18±0.17 respectively after 9 months of treatment. The Constant-Murley shoulder scores of typeⅠ, typeⅡand type Ⅳ were 65.81±2.09, 63.50±2.22 and 47.93±2.91 respectively before treatment, and increased to 88.56±2.11, 85.12±2.23 and 71.25±2.16 respectively after 9 months of treatment. Five patients were not satisfied with the appearance after treatment;6 patients had no obvious continuous callus passing through after 9 months of treatment, which was fracture nonunion.@*CONCLUSION@#The classification of middle clavicle fracture is more appropriate to the clinic, which has a certain clinical guiding significance for the selection of treatment methods and prognosis of middle clavicle fracture. Plastic splint is effective in the treatment of middle clavicle fracture without obvious displacement and overlapping displacement, and the incidence of complications is low. It can be popularized in clinic.

Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation / 中国天然药物

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.

Magnolol attenuates right ventricular hypertrophy and fibrosis in hypoxia-induced pulmonary arterial hypertensive rats through inhibition of the JAK2/STAT3 signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol is a com?pound isolated from Magnolia officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. METHODS ① Male SD rats (220 g) were randomly divided into 5 groups (n=10): the normoxia group, the hypoxia group, the hypoxia plus Magnolol (10 and 20 mg·kg-1·d-1) group, and the vehicle group. Rats in the normoxia group were kept in a normoxia environment for 4 weeks, while rats in the hypoxia group were kept in a hypoxic chamber (10％ O2). The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg-1 (ip) once a day for 4 weeks. At the end of 4 weeks, the heart function was assessed by Doppler echocardiography, and then the rats were anesthetized with sodium pentobarbital (30 mg·kg-1, ip). The RVSP was measured by the right heart catheterization method. The heart tissues were collected and dissected to calculate the index of RV remodeling (RV/LV+IVS, RV/tibial length, or RV/body weight). Part of the RV samples was fixed with 4％paraformaldehyde for morphological analysis, while other samples were frozen at-80℃for molecular studies (measurements of ANP, BNP,α-SMA, and col?lagen Ⅰ/Ⅲ mRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels). ② To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis, H9c2 or cardiac fibroblasts were divided into 7 groups: the control group, cells were cultured under normal conditions; the hypoxia group, cells were cultured under hypoxic condition (3％ O2);the hypoxia plus magnolol 10 mg·kg-1 group, magnolol10μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg-1 group, magnolol 20μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group, TG-101348 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group, JSI-124 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group, an equal volume of vehicle (DMSO) was added to the culture medium before the hypoxia treatment. At the end of the experiments, the cells were collected for morphological and molecular analysis. RESULTS In vivo, male Sprang-Daley rats were exposed to 10％ O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of RV remodeling index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3％ O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagenⅠ, collagenⅢandα-SMA). Administration of mag?nolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage / 神经科学通报·英文版

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1β, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

The development of auditory speech perception and spatial hearing abilities within one year after cochlear implantation in preschool prelingual deaf children / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the development of auditory speech perception and spatial hearing abilities within one year after cochlear implantation in preschool prelingual deaf children and the relationship between the two abilities. Methods: This retrospective study analyzed 31 preschool children with an average age of (2.3±1.2) years. All cases were assessed at pre-implant, 6 months and 12 months post-implant using the Infant-toddler Meaningful Auditory Integration Scale (IT-MAIS), the Meaningful Auditory Integration Scale (MAIS) and the Mandarin Early Speech Perception test (MESP) to evaluate their listening and speech perception abilities, and using the Speech,Spatial,and Other Qualities of Hearing Scale for Parents (SSQ-P) questionnaires to evaluate their speech perception and spatial hearing abilities. SPSS 23.0 was used for the statistical analysis. Results: All children performed better at 6 months and 12 months post-implant with IT-MAIS/MAIS, MESP than pre-implant, and the scoring rate continued to improve, with a significant difference (P<0.01). For the SSQ-P (Speech) and SSQ-P (Spatial) scores, the mean scores of pre-implant were (0.9±0.2) points and (0.8±0.3) points, those of 6 months post-implant were (4.6±0.2) and (2.6±0.3), and 12 months post-implant were (6.2±0.2) and (6.3±0.3), the scores of the two groups were significantly different at pre-implant, 6 months and 12 months post-implant (P<0.01). The growth rate of SSQ-P (Spatial) from pre-implant to 12 months post-implant was 675.3%, and the growth rate from 6 months post-implant to 12 months post-implant was 140.6%, the growth rate showed an significant increase compared with IT-MAIS/MAIS, MESP and SSQ-P (Speech).SSQ-P (Speech) and SSQ-P (Spatial) scores were moderate correlation at 12 months post-implant(r=0.465, P=0.008). Conclusions: Within one year after cochlear implantation, listening, speech perception and spatial hearing abilities of preschool prelingual deaf children could show a comprehensive, continuous and significant progress as the implantation time increasing. The growth rate of spatial hearing is greater than that of speech perception at 12 months post-implant, and the spatial hearing could still show rapid development characteristics after 6 months post-implant.

The Mitochondrial Ribosome Associated Protein Quality Control System and Diseases / 中国生物化学与分子生物学报

Protein synthesis is a complex process. Under certain circumstances, abnormal ribosome stalling will occur during translation, resulting in the inability to effectively recover the ribosome for the next round of translation. Nascent polypeptides arisen from the stalled ribosome are at risk of forming aggregate species, and disturbing protein homeostasis and contributing to development of diseases. The ribosome-associated protein quality control(RQC) pathway provides a rescue method for recovering of stalled ribosomes and for proteasomal degradation of nascent polypeptides obstructed on 60S subunits. The latest researches show that there are RQC rescue pathways on the surface of mitochondria (called mitochondrial ribosome-associated protein quality control, mitoRQC). Mitochondria are important organelles involved in energy production and metabolism in eukaryotic cells. More than 98% of mitochondrial proteins are encoded by nuclear genes and transported from the cytoplasm to mitochondria. These proteins are potential targets for mitoRQC, which works synergistically with the internal regulation system of mitochondria to maintain mitochondrial stability. In this review, we will focus on the recent progress on the RQC and mitoRQC pathway as well as their implications in the progression of diseases.

Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells / 亚洲男科学杂志(英文版)

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis: a prospective, randomized, controlled, single-center clinical study / 中华医学杂志(英文版)

BACKGROUND@#The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.@*METHODS@#This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients' nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.@*RESULTS@#The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.@*CONCLUSIONS@#In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients' mineral metabolism, inflammatory parameters, or body compositions.

Clinical efficacy and safety evaluation of diabetic nephropathy treatment with Yishen Huashi Granule combined with Tripterygium wilfordii polyglycosides Tablet / 中草药

Objective: To study the clinical efficacy and safety of Yishen Huashi Granule (YHG) combined with Tripterygium wilfordii polyglycosides tablet (TWP) in the treatment of diabetic kidney disease (DKD). Methods: A total of 92 DKD patients in the stage of III-IV were selected from the department of nephropathy of the Jiujiang Hospital of Chinese Medicine. These patients were randomly divided into the observation group (46 cases) and the control group(46 cases). The observation group was treated with conventional therapy combined with TWP, and the control group was treated with TWP combined with YHG based on conventional therapy, both groups were continuously treated for three months. The urinary microprotein, serum albumin, urea nitrogen, creatinine, triglyceride, total cholesterol, urine IgG4, and urinary retinol binding protein were detected before and after treatment. The TCM syndrome score was evaluated and recorded. Blood routine, liver function, cellular immunity were detected after treatment. The recurrence and metastasis events were followed up and recorded. Results: After treatment, the total effective rate of the control group and the treatment group were 73.91% and 86.96% respectively, and the difference between the two groups was statistically significant (P < 0.05). Moreover, the levels of urinary microprotein, urea nitrogen and creatinine were (178.65 ± 31.72) mmol/L, (7.63 ± 2.15) mmol/L and (85.68 ± 14.74) μmol/L, respectively, which were significantly lower in the treatment group when compared with control group (P < 0.05). After treatment, the levels of serum albumin, triglyceride, and total cholesterol in the treatment and control groups were significantly improved (P < 0.05). The serum albumin level in the treatment group was significantly higher than that in the control group (P < 0.05), and the TG and TC levels were significantly lower than that in the control group (P < 0.05). The urine IgG4, and urinary retinol binding protein in the observation group were significantly reduced than those in the control group (P < 0.05). The white blood cell, and CD4+ in the observation group were higher than those in the control group (P < 0.05). The AST, ALT, and CD8+ in the observation group were significantly reduced than those in the control group (P < 0.05). TCM syndrome score in the observation group were lower than that in the control group (P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion: YHG combined with TWP have the effect of increasing the efficacy and reducing the toxicity in the treatment of DKD.

Prognostic value of the C-reactive protein to albumin ratio in patients with colorectal cancer undergoing adjuvant chemotherapy / 中国综合临床

Objective:To evaluate the prognostic value of C-reactive protein (CRP) to albumin ratio (CAR) before and after adjuvant chemotherapy for colorectal cancer.Methods:From February 2013 to March 2014, the clinical data of 248 patients underwent radical resection of colorectal cancer combined with postoperative adjuvant chemotherapy in Department of Gastroenterology Surgery of the Affiliated Hospital of Southwest Medical University were retrospectively analyzed.The patients were followed up every 3 months within 2 years, once every six months after three years, and the deadline for follow-up was March 2019.Receiver operating characteristic (ROC) and Cox risk assessment were analyzed before, after and after chemotherapy.The optimal cut-off points of CAR before and after adjuvant chemotherapy were obtained by ROC curve. According to the optimal cut-off point, the patients were divided into high CAR group before chemotherapy and low CAR group before chemotherapy, high CAR group after chemotherapy and low CAR group after chemotherapy. The relationship between CAR and clinicopathological features and survival was compared before and after chemotherapy.Results:There was a positive correlation between CAR before adjuvant chemotherapy(0.23±0.05) and after chemotherapy (0.31±0.07) (r 0.382, P<0.001). Combined analysis of car before and after adjuvant chemotherapy the ROC curve area of CAR was 0.808, the sensitivity and specificity were 79.3% and 78.5%, respectively, which was higher than those of CAR before chemotherapy alone (the area under the curve was 0.776, the sensitivity and specificity were 78.1% and 66.2%, respectively, z=1.675, P<0.001) and CAR after chemotherapy (the area under the curve was 0.699, the sensitivity and specificity were 76.5% and 53.8%, Z=3.361, P<0.001). Cox risk assessment model single factor analysis and multivariate analysis showed that high CAR before chemotherapy ( HR=2.853, 95% CI 2.021-4.029, P<0.001) and and after chemotherapy ( HR=2.165, 95% CI 1.890-2.565, P<0.001) were independent risk factors for colorectal cancer prognosis. Conclusion:The combined detection of CAR before and after adjuvant chemotherapy is valuable in evaluating the prognosis of colorectal cancer.

Practice and reflections on integrated neurology curriculum in pre-clinical education / 中华医学教育探索杂志

Objective:To explore the practice and preliminary effects of "integrated neurology curriculum" for medical students before internship.Methods:The following 3 aspects were integrated together: teaching content, teaching faculty and teaching methods. Teaching contents are comprised of basic medical theories and extension of clinical knowledge; teaching faculty includes teachers that teach basic theories and many other clinical disciplines; teaching methods were composed of classroom teaching, case discussion and clinical internship. It is a 56-hour curriculum, with 40 hours for studying theories and 16 for clinical internship. 82 students in total had attended the course. Independent sample t-test was used to compare the scores of students in the same grade but had different course structures, and chi-square test was performed with SPSS 22.0 to compare the results of the satisfaction degree from questionnaires.Results:The average score of students was (84.7±9.3) for the courses of 2017-2018 academic year, significantly higher than that of the students who were in the same grade in previous three years. The results of satisfaction degree by the questionnaires showed that 38.6% of the students considered the integrated course to be very helpful in general, 47.7% of the students thought the case analysis part during class was helpful, and 31.8% of the students thought clinical internship was of great help to their medical study.Conclusion:The neurology curriculum based on integrated textbooks has achieved preliminary achievements in preclinical teaching practice, and the teaching group of the curriculum will continue to track the performance of medical students after entering neurology clinical internship, while further improving the quality of integrated courses in terms of teaching and assessment.

Network pharmacology study on anti-stroke of Xiaoshuan Tongluo formula based on systematic compound-target interaction prediction models / 药学学报

Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.

Two new mixed-ligand coordination polymers based on multi-N chelating ligand inhibit YAP expression and induce caspase-mediated spinal tumor cell apoptosis

Two new coordination polymers [Zn (bdc)(bpybzimH2)](DMF)0.5 (1, H2bdc=1,4-dicarboxybenzene, bpybzimH2=6,6′-bis-(1H-benzoimidazol-2-yl)-2,2′-bipyridine, DMF=N,N-dimethylformamide) and [Co (bpybzimH2)(sbc)]H2O (2, H2sbc=4-mercaptobenzoic acid) have been successfully prepared under solvothermal conditions using the multi-N chelating organic ligand bpybzimH2 as the foundational building block. In addition, the Cell Counting Kit-8 assay was conducted to evaluate the anti-proliferation activity of compounds 1 and 2 against human spinal tumor cells OPM-2. The cell viability curves showed that the two compounds have anti-proliferation activity on spinal tumor cells, and the activity of compound 1 is higher than compound 2. The annexin V-FITC/PI assay and western blot were used to detect the apoptotic percentage of OPM-2 cells incubated with compounds 1 and 2. The YAP protein expression and its role in cell apoptosis were further studied with qRT-PCR, immunoblotting, and flow cytometer.

Serum levels of miR‐21 and miR‐155 in T2DM + CHD patients and their relationship with lipid me‐tabolism／ / 心血管康复医学杂志

To explore serum levels of miR‐21 and miR‐155 in patients with T2DM complicated CHD and their relationship with lipid metabolism .Methods : A total of 134 T2DM patients treated in our hospital from 2016 to 2017 , were divided into T2DM + CHD group (n＝60) and pure T2DM group (n＝74).Blood glucose and blood lipid levels and serum miR‐21 and miR‐155 levels were measured and were compared between two groups .Results :There were no significant difference in general data , blood pressure , body mass index (BMI) , glycosylated hemo‐globin A1c (HbA1c) , plasma glucose and total cholesterol (TC) between two groups , P＞0. 05 all.Compared with pure T2DM group , there were significant rise in levels of triglyceride (TG) [ (1. 89 ± 0.92) mmol／L vs.(2. 75 ± 1.61) mmol／L] , LDL‐C [ (2.83 ± 0.79) mmol／L vs.(3. 52 ± 1.24) mmol／L] and serum miR‐21 [ (0. 93 ± 0. 15) vs.(1. 86 ± 0.24 )] , and significant reductions in levels of HDL‐C [ (1.35 ± 0. 34 ) mmol／L vs.(0. 94 ± 0.31 ) mmol／L] and serum miR‐155 [ (0. 95 ± 0.19) vs.(0. 27 ± 0. 10)] in T2DM + CHD group , P＝0.001 all.Multiva‐riate Logistic regression analysis indicated that TG , LDL‐C and miR‐21 were independent risk factors for T2DM +CHD (OR＝2. 800～4. 986 , P＜0.05 all) , while HDL‐C and miR‐155 were its independent protective factors (OR＝0.314 , 0.327 , P＜ 0.05 both).Pearson correlation analysis indicated that serum miR‐21 level was significant positively correlated with TG and LDL‐C levels ( r＝0. 415 , 0.506 , P＜0.05 or ＜0. 01) , and serum miR‐155 level was significant inversely correlated with TG and LDL‐C levels ( r＝ －0. 397 ,－0. 526 , P＜0.05 or ＜0. 01 ).Con‐clusion : Serum miR‐21 level was significant positively correlated with TG and LDL‐C levels , but serum miR‐155 level was significant inversely correlated with TG and LDL‐C levels ,