Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Neonatal hyperbilirubinaemia, clinically presenting as jaundice, is a ubiquitous and commonly a benign metabolic condition in newborn infants.It is a leading cause of hospitalization of neonates in the first week of life.Serum bilirubin has been considered as the most potent superoxide with the peroxyl radical scavenger activity.However, uncontrolled hyperbilirubinaemia or rapidly rising bilirubin can reach a neurotoxic concentration, potentially leading to central nervous system sequelae.Thus, the health status of jaundiced newborn infants is dependent on striking an appropriate balance between the protective effects of serum bilirubin and the risk of bilirubin neurotoxicity.In order to standardize the management of neonatal hyperbilirubinemia (jaundice), many countries have developed clinical practice management guidelines.This review sorted out and briefly interpreted the main contents of clinical management guidelines for neonatal hyperbilirubinemia drafted by the American Academy of Pediatrics and other countries, aiming to provide references of clinical diagnosis and treatment practice to domestic pediatrician.

Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.

An epidemiological investigation was carried out on a local cluster of outbreak caused by imported cases of Coronavirus Disease 2019 (COVID-19) in rural areas of Chengdu in December 2020, to find out the source of infection and the chain of transmission. According to
COVID-19 ; Disease Outbreaks ; Epidemics ; Humans ; Quarantine ; SARS-CoV-2

Objective:To explore the effect of perioperative whole-course closed-loop temperature management system for prevention of hypothermia in elderly patients with femoral neck fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 120 elderly patients with femoral neck fracture admitted to Chengdu First People's Hospital from January 2020 to December 2020. There were 48 males and 72 females, aged 60-79 years［（68.3±5.0）years］. All patients underwent total hip arthroplasty. Heat warming with the whole-course closed-loop temperature management system was applied in 40 patients（closed-loop group）, with the medical heating mattress in 40 patients（heat preservation group）, and with the quilt in 40 patients（control group）. The core body temperature of the three groups was recorded 8 minutes after wearing the temperature sensor（T0）, immediately after induction of anesthesia（T1）, 30 minutes after induction of anesthesia（T2）, 60 minutes after induction of anesthesia（T3）, at the end of surgery（T4）, and 20 minutes after entering the postanesthesia care unit（PACU）（T5）. The thrombin time（TT）, prothrombin time（PT）and activated partial thromboplastin time（APTT）were compared among groups before operation and at T4. The incidence of intraoperative hypothermia, incidence of shivering during PACU, incidence of surgical site infection, extubation time（from the day of drug withdrawal to the time of tracheal tube removal）, length of hospital stay（from the day of operation to the time of discharge）and adverse reactions related to the devices were compared among groups.Results:There was no statistically significant difference in core body temperature among three groups at T0（ P>0.05）. The core body temperature in closed-loop group［（36.61±0.28）℃］was higher than that in heat preservation group［（36.45±0.28）℃］and control group［（36.44±0.27）℃］at T1（ P<0.05）, but no statistically significant difference was found in core body temperature between heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group［（36.46±0.28）℃,（36.40±0.30）℃,（36.45±0.37）℃,（36.50±0.27）℃］was higher than that in heat preservation group［（36.32±0.31）℃,（36.24±0.26）℃,（36.28±0.30）℃,（36.24±0.31）℃］and control group［（36.12±0.30）℃,（35.98±0.28）℃,（35.73±0.31）℃,（35.81±0.32）℃］at T2-T5（ P<0.05）, and a higher temperature was found in heat preservation group than control group（ P<0.05）. The core body temperature in closed-loop group was increased at T1 compared to that at T0（ P<0.05）, while there was no statistical difference at T0 and T1 in heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group showed no significant difference at T2-T5 and T0（ P>0.05）, while the core temperature in heat preservation group and control group was decreased at T2-T5 compared to that at T0（ P<0.05）. The core body temperature in closed-loop group was within the set target temperature range. There was no statistically significant difference in TT, PT and APTT among the three groups before operation（ P>0.05）. At T4, the levels of TT, PT and APTT in closed-loop group［（18.9±1.7）seconds,（11.9±0.7）seconds,（35.5±3.3）seconds］and heat preservation group［（18.8±1.7）seconds,（11.6±0.8）seconds,（32.8±2.7）seconds］were shorter than those in control group［（20.9±1.3）seconds,（13.0±0.8）seconds,（35.7±3.4）seconds］（ P<0.05）. At T4, the levels of APTT in closed-loop group and heat preservation group were longer than those before operation（ P<0.05）. At T4, the levels of TT, PT and APTT in control group were longer than those before operation（ P<0.05）. There was no significant difference in the incidence of intraoperative hypothermia or shivering during PACU between closed-loop group［18%（7/40）, 3%（1/40）］and heat preservation group［33%（13/40）, 8%（3/40）］（ P>0.05）, which were lower than those in control group［75%（30/40）, 33%（13/40）］（ P<0.05）. There was no significant difference in the extubation time between closed-loop group［（12.5±3.6）minutes］and heat preservation group［（13.2±3.9）minutes］（ P>0.05）, which was shorter than that in control group［（16.6±4.0）minutes］（ P<0.05）. The incidence of surgical site infection and length of hospital stay were statistically insignificant among the three groups（ P>0.05）. No adverse reactions such as allergic reaction or pressure ulcers occurred in the three groups. Conclusion:For the elderly patients with femoral neck fracture, the perioperative whole-course closed-loop temperature management system can effectively maintain the core body temperature, improve coagulation function, prevent hypothermia, reduce shivering and shorten the extubation time, without increasing the risk of other adverse events, so the system can be safely used in clinical practice.

Objective: To assess the clinical characteristics and identify the risk factors in the acute myocardial infarction (AMI) patients complicating with ventricular septal rupture (VSR). Methods: A retrospective study was performed on 96 AMI patients complicating with VSR, who were hospitalized in the Second Xiangya Hospital of Central South University, Hunan Provincial Peoples′ Hospital, the First Affiliated Hospital of University of South China, the Second Affiliated hospital of University of south China, Xiangtan Central Hospital from December 2007 to May 2017. There were 46 females and the age was (66.2±10.7) years (from 43 to 90 years). Patients were divided into in-hospital survival group (n=64) and in-hospital death group (n=32). The 96 patients were also divided into the early death group (survived ≤2 weeks after admission, n=50) and non-early death group (survived>2 weeks after admission, n=46). Multivariate logistic regression was used to analyze the independent risk factors of the early death. Results: Location of VSR was available in 71 patients, VSR was located at the apical or anterior septum near the apical region in 64.0% (32/50) patients with the anterior AMI, VSR was located at the posterior wall and basal inferior segment in 57.1% (12/21) patients with non-anterior AMI. Compared to the in-hospital survival group, patients in the in-hospital death group were older ((69.6±11.3) years vs. (64.6±10.1) years, P=0.031), incidence of non-ventricular aneurysm (71.9% (23/32) vs. 37.5% (24/64), P=0.001) and anterior AMI (84.4%(27/32) vs. 62.5%(40/64), P=0.028) was significantly higher in the in-hospital death group than in the in-hospital survival group. The comparison between the early death group and non-early death group showed that older age, female, no history of angina or myocardial infarction, Killip grade>Ⅲ, and non-ventricular aneurysm were related to increased risk of the early mortality in this patient cohort. Logistic regression analysis revealed that female (OR=5.109,95%CI 1.19-22.00, P=0.012), no history of angina or myocardial infarction (OR=23.34, 95%CI 3.44-158.37, P=0.001), Killip grade>Ⅲ(OR=5.35, 95%CI 1.26-22.66, P=0.019) and non-ventricular aneurysm (OR=6.30,95%CI 1.67-23.73, P=0.005) were independent risk factors for early death in this patient cohort. Conclusion The risk factors of in-hospital death include older age, non-ventricular aneurysm and anterior AMI. Female, no history of angina or myocardial infarction, Killip grade>Ⅲ and non-ventricular aneurysm are independent risk factors for the early death of AMI patients complicating VSR.

Objective To investigate the impact of 1,25(OH)2D3 on histological changes and activation of STAT3 in BLM?induced pulmonary fibrosis mice. Methods 30 male C57BL/6 mice were randomly divided into control group ,BLM group and BLM+VD group. Mice in BLM group and BLM+VD group received intratracheal injection of BLM(3 U/kg). Control group were intratracheally injected equal volume of sterile saline. From the first day after the surgery,mice in BLM+VD group received intraperitoneal injection of VD (5μg/kg·d). After 21 days, H&E and Masson′s trichrome staining were carried out. Aschroft score were used to evaluate histological changes in lungs. IL?6,IL?4 and INF?γin BALF were assessed by Elisa. p?STAT3,α?SMA and Collagen I were detected by western blot (WB) and immunohistochemistry. Results Fibrosis score and level of α?SMA,Collagen I in BLM group were significantly higher than that in control group (P < 0.05). However ,treatment with VD effectively at?tenuated fibrosis (P<0.05). IL?6 and IL?4 increased while INF?γwas decreased in BALF of BLM group (P<0.05). VD could ameliorate these changes. Upregulation and neuclear translocation of p?STAT3 were observed in BLM group,while VD intervention could inhibit phosphorylation of STAT3. Conclusions VD attenuate BLM?induced pulmonary fibrosis and regulate inflammatory cytokines probably by blocking STAT3 activation.

Objective To study the relative risk factors of simultaneous gastric and colonic polyps,pro-vide theoretical basis for simultaneous gastrointestinal endoscopy monitoring for high-risk population. Methods Retrospective analysis on the patients with a total of 506 cases in the department of gastroenterology of Zhujiang Hospital from 2014 to 2016 and diagnosis gastric polyps or colonic polyps. Adopt cases-control research,the pa-tients(138)with gastric polyps and colonic polyps were divided into case group,the patients(99)with gastric polyps or colonic polyps(269)were divided into control group.Results The colonic polyps group is mainly com-posed of male(69.1%);while gastric polyps group is mainly composed of female(76.8%);The proportion of the patients over 50 years old with gastrointestinal polyp is higher(81.9%).The proportion of Hp infection in the colon-ic polyps group is higher(43.1%),followed by the cases group(31.9%).The composition of the pathological types between gastric polyps group,colonic polyps group and cases group is similar,while there is no correlation on the pathological types between gastric polyps and colonic polyps in the cases group. Conclusion The male patients who diagnosis gastric polyps should perform colonoscopy,the gastric polyps patients who is Hp infection should per-form colonoscopy,the patients over 50 years old are suggested to perform gastrointestinal endoscopy. There is no correlation on the pathological types between gastric polyps and colonic polyps,further studies will be conducted to expand the study sample size.

Objective To verify the correlation between rs17118 polymorphism of xyluloknase homolog (XYLB) gene and risk of ischemic stroke in a Chinese Han population.Methods A case-control study design was used.The case group was the patients with first-ever ischemic stroke and the control group was the healthy subjects from hospital physical examination.Taqman probe fluorescence quantitative polymerase chain reaction technique was used to detect the genotype distribution of rs17118 C/A polymorphisms.Results A total of 475 patients with ischemic stroke and 483 controls were enrolled in the study.The proportion of hypertension (67.9％ vs.22.2％;x2 =292.982,P ＜ 0.001) and diabetes (24.2％ vs.7.3％;x2 =25.864,P ＜ 0.001),as well as the levels of triacylglycerol (1.649 ± 1.126 mmol/L vs.1.157 ±1.480 mmol/L;t=3.592,P＜0.001),and low-density lipoprotein cholesterol (3.499 ± 1.163 mmol/L vs.3.105 ± 0.627 mmol/L;t =-6.227,P ＜ 0.001) in the case group were significantly higher than those in the control group,but the total cholesterol level was significantly lower than that in the control group (5.144 ± 1.296 mmol/L vs.5.491 ± 1.335 mmol/L;t =4.650,P ＜ 0.001).The AA genotyp e (11.4％ vs.7.5 ％;x2 =6.136,P =0.016) and A allele (32.3 ％ vs.26.4％;x2 =8.093,P =0.005) frequencies in the case group were significantly higher than those in the control group.Multivariatelogistic regression analysis showed that after adjusting for traditional risk factors,the risk of ischemic stroke in AA genotype carriers was 1.97 times of the CC genotype carriers (odds ratio 1.971,95％ confidence interval 1.040-3.736,P=0.038).Conclusions The rsl7118C/A polymorphism of XYLB gene may be associated with the risk of ischemic stroke in the Chinese Han population.