Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Lacunar stroke (LS) is one of the subtypes of small cerebral vascular disease. Recent studies have shown that LS has a high risk of cognitive impairment, which imposes a heavy burden on patients, their families and society. However, at present, there is a lack of comprehensive discussion on the related factors, pathogenic mechanism, clinical features, prevention and treatment of cognitive impairment in LS patients. Therefore, this article reviews the relationship between LS and cognitive impairment, in order to provide clinical basis for early prevention and rehabilitation plan, and improve long-term follow-up awareness and comprehensive management ability of cognitive function in LS patients.

ObjectivePneumonia is an infectious inflammation of the alveoli， distal airway， and interstitium caused by bacterial， viral， and other pathogens. Maxing Shigantang， originated from Treatise On Cold Damage Diseases， is a classic prescription for treating pneumonia， with significant clinical efficacy. However， its treatment mechanism is still elusive. MethodIn that paper， the transcriptome-based multi-scale network pharmacology was used to reveal the overall pharmacological mechanism of Maxing Shigantang in treating pneumonia from six scales of tissue， cell， pathological process， biological process， signaling pathway， and target. ResultAt the tissue level， Maxing Shigantang mainly acted on the focal tissue of pneumonia-lung and the main inflammatory immune tissues-blood and spleen. Analysis of cell， pathological process and biological process suggested that Maxing Shigantang could treat pneumonia by reversing inflammatory and immune functions and improving cardiopulmonary and vascular injury caused by pneumonia. Analysis of signaling pathway and target showed that Maxing Shigantang regulated inflammatory immune response pathways such as "coronavirus disease-COVID-19" and "Toll-like receptor signaling pathway"， and related targets such as "MAPKAPK3" and "NRG1". ConclusionThis paper， from molecular to tissue levels， indicated Maxing Shigantang treated pneumonia mainly by regulating inflammatory immune response and improving cardiopulmonary and vascular injury.

Objective:To investigate the efficacy of Kechuanning combined with western medicine on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its effects on serum amyloid A, interleukin 1β and procalcitonin levels. Methods:A total of 104 patients with AECOPD who received treatment in Yongkang Hospital of Traditional Chinese Medicine from January 2019 to December 2020 were included in this study. They were randomly assigned to receive either symptomatic treatment with western medicine alone ( n = 52, control group) or symptomatic treatment with western medicine combined with Kechuanning ( n = 52, observation group). Therapeutic effects, latency to clinical symptom relief, pre- and post-treatment pulmonary function, serum inflammatory factor levels, and blood gas analysis indexes were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [86.54% (45/52) vs. 67.31%(35/52), χ2 = 4.99, P < 0.05]. Latency to rale disappearance, latency to cough disappearance, length of hospital stay in the observation group were (8.25 ± 1.38) days, (10.05 ± 1.53) days, and (12.65 ± 2.28) days, which were significantly shorter than those in the control group [(9.41 ± 1.46) days, (12.19 ± 1.61) days, (14.36 ± 2.14) days, t = 4.16, 6.98, 3.61, all P < 0.05]. After treatment, forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1), and FEV 1/FVC value in the observation group were (1.88 ± 0.5) L, (64.13 ± 5.72)%pred, (59.43 ± 5.57)%, respectively, which were significantly higher than those in the control group [(1.65 ± 0.51) L, (60.22 ± 5.60)% pred, (54.16 ± 5.19)%, t = 2.17, 3.52, 4.99, all P < 0.05]. Arterial partial pressure of oxygen (PaO 2) and blood oxygen saturation (SpO 2) in the observation group were (9.18 ± 0.89) kPa and (96.26 ± 2.13)%, respectively, which were significantly higher than those in the control group [(8.74 ± 0.76) kPa, (94.07 ± 2.08)%, t = 2.71, 5.305, both P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) in the observation group was significantly lower than that in the control group [(7.32 ± 0.27) kPa vs. (7.63 ± 0.32) kPa, t = 5.34, P < 0.05]. Serum amyloid protein, interleukin-1β and procalcitonin levels in the observation group were (43.84 ± 6.15) mg/L, (3.24 ± 0.51) μg/L, (1.55 ± 0.37) ng/L, respectively, which were significantly lower than those in the control group [(55.26 ± 3.46) mg/L, (4.19 ± 0.56) μg/L, (2.03 ± 0.46) ng/L, t = 9.23, 9.04, 5.86, all P < 0.05]. Conclusion:Kechuanning as an adjuvant therapy for AECOPD can greatly improve lung function and hypoxia, alleviate clinical symptoms, reduce inflammatory reactions, and have a definite clinical effect. The study is innovative and scientific and is worthy of clinical reference.

Objective:This paper intends to explore the clinical efficacy and safety of the refined extroperitoneal intrafascial laparoscopic radical prostatectomy in patients with localized prostate cancer.Methods:The data of 107 patients with localized prostate cancer who were underwent laparoscopic radical prostatectomy in our hospital from July 2013 to January 2020 were analyzed retrospectively. According to the operation methods, the patients were divided into two groups: the refined intra fascial resection group (59 cases) and the conventional interfascial neurovascular bundle reservation group(48 cases). There was no significant different comparing the age [(61.8±8.9) years vs. (62.2±8.1) years, P=0.71], body mass index (BMI) [(24.8±1.3) kg/m 2 vs.(24.3±1.4) kg/m 2, P=0.89], preoperative total prostate specific antigen (PSA) [(6.8±0.9) ng/ml vs. (7.2±1.1) ng/ml, P=0.44], prostate volume [(47.9±18.4) ml vs. (48.3±17.9) ml, P=0.67] between the modified group and the conventional group. The clinical stage of the two groups was both in cT 1-T 2aN 0M 0, and the preoperative Gleason score was less than or equal to 7 ( P=0.76). In the improved group, the bilateral pelvic floor fascia was not dissected, the dorsal deep vein complex was not sutured, the denonvillier fascia was kept intact, the prostate was dissected by intrafascial technique, and the bilateral vascular and nerve bundles were completely preserved. After anastomosing the urethra and bladder neck, the bilateral prostate fascia, the pubic bladder-prostate ligament, DVC and the anterior wall of bladder neck were continuously sutured with 3-0 barbed wire in order to anatomically reconstructe the anterior suspension system. The preoperative data, intraoperative condition, postoperative pathological stage, positive margin rate and postoperative 6-month's follow-up, especially incontinence and erectile function were compared between the two groups. Results:There was no significant difference between the two groups in the basic clinical data, intraoperative bleeding volume[(90.6±26.4)ml vs.(105.3±34.1)ml, P>0.05], prostate-specific antigen 6 weeks after operation[(0.08±0.06)ng/ml vs.(0.09±0.07) ng/ml, P>0.05], postoperative pathological stage and positive margin rate(12.5% vs. 11.9%, P>0.05). In the early postoperative stage, patients performed a significantly better continence. Continence rate in 1 week: 16.7%(8/48) vs. 52.5%(31/59)( P<0.05), in 1 month: 29.2%(14/48)vs. 64.4%(38/59)( P<0.05), and in 3 month 52.1%(25/48) vs. 77.9%(46/59)( P<0.05). And also a better erectile function recovery rate in 1 month: 8.3%(4/48) vs. 23.7%(14/59)( P<0.05), in 3 month: 27.1%(13/48) vs. 49.2%(29/59)( P<0.05), in refined intrafascial group, but that was not significant different between the two groups 6 months after operation. Conclusion:The refined intrafascial laparoscopic radical prostatectomy can completely reconstruct the anatomic structure adjacent to urethra, and preserve utmostly the pelvic floor muscle, prostate fascia and neurovascular bundle, which are supposed to facilitate the revovery of urinary incontinence and erectile dysfunction in the early postoperative period.

Objective:To investigate the correlation between item d560 of the International Classification of Functioning, Disability and Health (ICF) and the swallowing function of convalescing stroke patients.Methods:A total of 140 convalescent stroke survivors were evaluated for dysphagia using the ICF-d560 and the modified Watian drinking water test. Linear regression was used to analyze the influence of clinical factors when choosing a swallowing function assessment scale. Spearman correlation was computed to explore the correlation between ICF item d560 and the modified Watian drinking water test.Results:According to the ICF-d560 results, 10% of the patients had a mild disorder, with another 37.1% moderate, 29.3% severe and 23.6% completely dysphagic. The corresponding percentages according to the improved Watian drinking water test were 44.3% mild, 31.4% moderate and 24.3% severe. The total correlation coefficient between the two sets of results was 0.86, which was related to the stroke type, age, gender and stroke risk factors. The correlation coefficient of the cerebral infarction group was significantly higher than the cerebral hemorrhage group′s coefficient, and that of the women was slightly higher than that of the men. The strength of the correlation increased with age. The correlation coefficient was 0.84 among both diabetics and hypertension sufferers.Conclusions:Results from the ICF-d560 and the modified Wada drinking water test correlate well, which can provide a screening tool for swallowing function based on the ICF theoretical framework.

Objective: To investigate the nutritional status of children with autism spectrum disorders, and to provide a reference for improving their nutritional status. Methods: 120 children with autism spectrum disorder who were treated in the rehabilitation center of Affiliated Children s Hospital of Zhengzhou University from September 2016 to September 2018 were selected as case group,and 120 normal children in the physical examination center of the same hospital were selected as the healthy group.The children s status was assessed by using the Clancy Autism Behavior Scale(CABS), and the serum nutrients levels were compared between these two groups. Results: Compared with the healthy group,the Vitamin A[(83.44±9.20,59.45±4.42)mg/L],Vitamin B6[(64.15±11.22,32.02±5.75)mg/L],Vitamin C[(60.62±10.26,47.63±13.12)mg/L],protein[(120.45±30.51,104.46±9.38)g/L], iron[(134.25±18.16,112.17±6.02)mg/L], calcium[(72.96±10.62,66.57±4.11)mg/L], zinc[(70.85±5.76,62.52±10.66)mg/L] and folic acid[(31.38±6.77,20.29±6.26)mg/L], eicosapentaenoic acid(EPA)[(0.72±0.22,0.55±0.14)μmol/L], decosahexaenoic acid(DHA)[(1.54±0.35,1.22±0.26)μmol/L] and arachidonic acid(AA)[(5.51±0.76,5.03±0.16)μmol/L] were lower(t=25.75，27.92，8.54，5.49，12.64，6.30，7.53，13.18，7.14，8.04，6.77，P<0.05), the low body weight(49.17%,63.33%) and wasting(38.33%,46.67%) in autism spectrum disorder group were higher significantly(χ2=4.89，6.71，P<0.05). Conclusion The nutritional status of children with autism spectrum disorder is different from that of normal children. The lack of serum nutrients will lead to a high incidence of malnutrition.

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.

Objective: To evaluate the results of catheter ablation of ventricular tachycardia (VT) via direct ventricle puncture access in patients without traditional approach. Methods: Two idiopathic left fasicular VT patients with mechanical aortic and mitrial valve repalcement and 1 patient with right ventricular originated VT post mechanical tricuspid valve repalcement from March 2010 to July 2012 in Fuwai hospital were enrolled in this study. For left fasicular VT patients, catheter ablation was performed using transapical left ventricular access via minithoracotomy. For the patient with right ventricular originated VT, catheter ablation was performed via percutaneous right ventricle puncture at xiphoid. Abaltion was guided under EnSite NavX mapping system. The feasibility of VT ablation via direct ventricle puncture access and long-term VT recurrence were investigated. Results: Catheter ablation was successful in all patients, and all clinical VTs were eliminated. The procedure time was 53, 62 and 74 minutes respectively with radiation time 11, 16 and 20 minutes. The ablation time was 130, 170 and 240 seconds individually. No procedure related complication occurred. After a follow-up time of 76, 55 and 82 months respectively, no VT recurrence was found in patients with left fasicular VT. New-onset VT with different morphology with previous VT was recorded in the patient with right ventricular originated VT, subcutaneous implantable defibrillator was implanted finally in this patient. Conclusions For patients with endocardial origined ventricular arrhythmias which could not be ablated via traditional approaches, direct ventricle puncture access with hybrid techniques provides a new approach foreliminating VTs in these patients.

Objective To explore the clinical and imaging efficacies of stent-assisted embolization and flow diversion in the treatment of intracranial aneurysms ≥10 mm. Methods Eighty-six patients with intracranial aneurysms≥10 mm, admitted to our hospital from January 2012 and February 2018, were chosen in our study; all 22 patients with ruptured aneurysms accepted stent-assisted embolization. Singular stent-assisted embolization was used in 55 patients, multiple stent-assisted embolization was used in 18 patients, and flow diversion was used in 13 patients. The immediate postoperative complete occlusion rate, complication incidence, and clinical and imaging follow-up data were retrospectively analyzed. Results (1) Results of immediate postoperative complete occlusion:Raymond grading I was noted in 56 patients, grading II in 6 patients, and grading III in 24 patients. Significant differences on immediate postoperative complete occlusion rates were noted among the three group (P<0.05); one patient had intra-stent thrombosis in the patients from singular stent-assisted embolization group, one patient with middle cerebral artery aneurysm had contralateral muscular dysplasia resulted from perforator occlusion and one patient with basal aneurysm had dysarthria resulted from perforator lesion in the patients from multiple stent-assisted embolization group; no perioperative complication was noted in patients from flow diversion group. (2) The prognosis of 86 patients was good;imaging follow-up results showed that 32 patients had occlusion, 7 had neck residue and 16 had recurrence in the singular stent-assisted embolization group; 11 patients had occlusion, one had neck residue and 6 had recurrence in the multiple stent-assisted embolization group; 11 patients had occlusion and 2 had neck residue in the flow diversion group; there were no statistically significant differences in follow-up results of aneurysms among the three groups (P>0.05). Conclusion Both flow diversion and stent-assisted embolization are effective methods for treatment of intracranial aneurysms≥10 mm.