The dichotomous role of immunoproteasome in cancer: Friend or foe?

Immunoproteasome is a variant of proteasome with structural differences in 20S subunits optimizing them for the production of antigenic peptides with higher binding affinity to major histocompatibility complex (MHC)-I molecules. Apart from this primary function in antigen presentation, immunoproteasome is also responsible for the degradation of proteins, both unfolded proteins for the maintenance of protein homeostasis and tumor suppressor proteins contributing to tumor progression. The altered expression of immunoproteasome is frequently observed in cancers; however, its expression levels and effects vary among different cancer types exhibiting antagonistic roles in tumor development. This review focuses on the dichotomous role of immunoproteasome in different cancer types, as well as summarizes the current progression in immunoproteasome activators and inhibitors. Specifically targeting immunoproteasome may be a beneficial therapeutic intervention in cancer treatment and understanding the role of immunoproteasome in cancers will provide a significant therapeutic insight for the prevention and treatment of cancers.

Development and validation of caregivers′knowledge-attitude-practice scale on safety precautions of children′s falling from bed in hospital / 中国实用护理杂志

Objective:To develop a scale of caregivers′ knowledge, attitude and practice (KAP) on safety precautions of children′s falling from bed in hospital, and test its reliability and validity.Methods:Based on the theory of KAP, the item pool was constructed by literature review and expert consultation. A convenient sampling method was used to investigate 380 caregivers of children admitted to Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiao Tong University in May 2021. The reliability and validity of the scale was tested. Critical ratio method and correlation analysis method were used for item analysis of the scale. Validity analysis was conducted by detecting content validity and construct validity; reliability analysis was conducted by detecting internal consistency reliability and split-half reliability.Results:The formal scale finally developed comprised 17 items in 3 dimensions on knowledge, attitude and practice. The Cronbach′s α coefficient and split-half reliability of the overall scale were 0.739 and 0.841. The content validity of the scale was 0.991, and the content validity of each item was 0.890-1.000. Exploratory factor analysis has extracted 3 common factors, and the cumulative variance contribution rate was 60.57%.Conclusion:The scale of caregivers′ KAP on safety precautions of children′s falling from bed in hospital has good reliability and validity, and can be used as a tool to evaluate the knowledge, willingness or behavior of caregivers' participation in preventing falls.

WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

The analysis of sensitivity and specificity of Humpty Dumpty pediatric fall assessment tool for hospitalized children / 中国实用护理杂志

Objective To determine the sensitivity and specificity of the Humpty Dumpty Fall Scale (HDFS) in predicting the falls in hospitalized children. Methods A retrospective matched case-control study was conducted. A chart review of 52 pediatric cases who fell and 52 controls who did not fall, were pair-matched by age, gender and diagnosis and matching ratio of 1∶1. The HDFS was used to evaluate the risk factors. Results The area of the ROC curve was 0.610. When the cutoff point of HDFS was 16, the sensitivity of it was 0.558, and the specificity was 0.635. There was a significant difference in two groups when the cutoff point was 13 (P<0.05), the score in fall case and non-fall case was (15.77 ± 1.46), (15.22 ± 1.21) points. Conclusions The HDFS can identify high risk of falls in hospitalized children in some degree. The optimal operating point is 13. The theoretical diagnostic value of the scale is at a low level. Further research is needed to verify or to improve the assessment tool that contribute to fall reduction.

The analysis of sensitivity and specificity of Humpty Dumpty pediatric fall assessment tool for hospitalized children / 中国实用护理杂志

Objective@#To determine the sensitivity and specificity of the Humpty Dumpty Fall Scale (HDFS) in predicting the falls in hospitalized children.@*Methods@#A retrospective matched case-control study was conducted. A chart review of 52 pediatric cases who fell and 52 controls who did not fall, were pair-matched by age, gender and diagnosis and matching ratio of 1∶1. The HDFS was used to evaluate the risk factors.@*Results@#The area of the ROC curve was 0.610. When the cutoff point of HDFS was 16, the sensitivity of it was 0.558, and the specificity was 0.635. There was a significant difference in two groups when the cutoff point was 13 (P<0.05), the score in fall case and non-fall case was (15.77 ± 1.46), (15.22 ± 1.21) points.@*Conclusions@#The HDFS can identify high risk of falls in hospitalized children in some degree. The optimal operating point is 13. The theoretical diagnostic value of the scale is at a low level. Further research is needed to verify or to improve the assessment tool that contribute to fall reduction.

The diagnosis value and prognosis analysis of systematic ultrasound examination in fetal lung disease / 中国医师杂志

Objective To explore the clinical significance and diagnosis value of ultrasonography for fetal lung disease.Methods A total of 61 cases of fetal lung disease was diagnosed and the data were retrospectively analyzed.Results In the 61 fetus of lung disease,(1) there were 31 fetuses with congenital cystic adenomatoid adenomatoid malforamation (CCAM),the ultrasound found that there were mass in fetus lung,they were mixed echo or large cyst or more little cyst or a hyperechoic in the mass.Among them,there were 2 cases of type Ⅰ,16 cases of type Ⅱ,and 13 cases of type Ⅲ;21 cases were labored,who were CCAM-confirmed by pathology,3 fetus masses were disappeared,7 cases were CCAM-confirmed with magnetic resonance (MR) after birth.(2) There were 19 fetuses with pulmonary sequestration (PS),the sonography was slightly hyperechoic mass in the lung,including 7 cases of induced labor and confirmed by pathology as PS,and 4 cases of mass disappeared,8 cases confirmed by MR or computed tomography (CT) after birth.(3) There were 6 cases of congenital diaphragmatic hernia,the abdomnial viscera was seen in the chest,5 cases were induced labor,and 1 survived after operation.(4) There were 5 cases of pleural effusion (PE),4 cases were induced labor and 1 case of PE disappeared.Conclusions Systemic prenatal ultrasonographic examination is an reliable method which can be short-term follow-up to observe the progress and the outcome,and to provide valuable information for clinical prognosis.

Accelerating the professional clinical research team building in the process of transforming towards research-oriented hospitals / 上海交通大学学报（医学版）

Building a professional clinical research team inside hospitals is in favor improving their research abilities,accelerating the clinical discipline construction,improving their comprehensive influence.Also it fits the objective of general hospital development under gate-keeping system.Now in domestic,the percentage of professional research staff in large hospitals accounts was much less than the international level.The main reasons included the misunderstanding of constructing the research-oriented hospitals,insufficient human resources enrollment,less attractive environment to the highlevel researchers and the absence of relevant degree training programs.To enhance the construction of research-oriented hospitals,it's of key importance to build the professional research team in hospitals.Besides,the hospital has to update management conception,broaden the channels of talent cultivation,grasp the development of the subject accurately and interact with the basic medicine and public health subject,increase the financial investment and perfect the relevant management regulations.

Effect of fluvastatin on the expressions of caspase-12, CHOP and JNK in ischemia-reperfusion brain injury in rats / 中国医师杂志

Objective To investigate the effect of fluvastatin on the expressions of caspase-12,CCAAT/enhancer-binding protein homologous protein(CHOP), and c-Jun N-terminal kinases (JNK) in ischemia-reperfusion brain injury in rats.Methods Forty two rats were randomly divided into sham operation group (6 rats), ischemia-reperfusion (I/R) group (18 rats), and fluvastatin (Flu) group (18 rats).The rats of I/R and Flu groups were molded by modified Longa intraluminal thread, then put to death at 2 h occlusion and 24 h reperfusion point.Expressions of caspase-12, CHOP, and JNK were detected with immunohistochemistry and Western blot.Results Immunohistochemistry and Western blot showed that the expressions of caspase-12, CHOP, and JNK were increased at 24 h reperfusion.Compared to I/R group, the expressions of caspase-12 and CHOP in Flu group were decreased significantly (all P ＜0.01);and the expression of JNK had no difference between I/R and Flu groups(P ＞ 0.05).Conclusions The increased expression of caspase-12, CHOP, and JNK showed that endoplasmic reticulum stress was involved in the pathological process of ischemia-reperfusion brain injury.Fluvastatin could inhibit the expression of caspase12 and CHOP, and could delete endoplasmic reticulum stress (ERS) in ischemia-reperfusion brain injury.

Study of cerebrovascular reserve capacity in obstructive sleep apnea-hypopnea syndrome / 中国综合临床

Objective To assess cerebrovascular reserve capacity in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods One hundred and fourteen patients with OSAHS and 43 normal persons were enrolled in this study.The patients were divided into mild,moderate,severe according to apnea hypopnea index (AHI) and LSaO2 (lowest arterial oxygen saturation).All the patients and normal persons were routinely examined using transcranial Doppler (TCD) and end-tidal carbon dioxide partial pressure(ETCO2) to evaluate cerebrovascular reserve.Hypercapnia was induced by inhaling the CO2 which produced by the patients themselves,and hypocapnia was elicited by voluntary hyperventilation.Results CVR in the severe and moderate OSAHS were significantly lower than that in the control group [ (1.80 ± 1.34) ％/mm Hg and (1.43 ±1.05)％/mm Hg vs (2.93 ±0.93)％/mm Hg,P ＜0.05] when patients in the condition of hypocapnia.And there was no significant difference on CRV between the mild OSAHS group and control group [ (2.53 ±1.83 ) ％/mm Hg vs ( 2.93 ± 0.93 ) ％/mm Hg,P ＞ 0.05 ].When patients in the condition of Hypercapnia,CRV in the severe and moderate OSAHS were also significantly lower than that in the control group [ ( 1.83 ±1.32) ％/mm Hg and (1.08 ± 1.00)％/mm Hg vs (3.32 ± 1.53)％/mm Hg,P ＜ 0.05),AHI was negatively correlated with the cerebrovascular reserve at the condition of hypercapnia and hypocapnia (r=-0.665,-0.721; P ＜ 0.05 ).Conclusion Inhaling CO2 is a effective method for assessing CVR.Cerebrovascular reserve capacity is associated with AHI.Reduced CVR causes hemodynamics change being severe hypoxia in the moderate and severe OSAHS.

The clinical feature and gene mutation of three pedigrees with spinocerebellar ataxia MA / 中国医师杂志

Objective To investigate the clinical features and the gene mutation of patients with spinocerebellar ataxia type3 and type7.Methods The trinucleotide repeat mutations were detected by polymerase chain reaction (PCR),agarose gel electrophoresis method,and DNA sequencing in 13 patients,4 related members and 4 common members from 3 spinocerebellar ataxia families.Results Among the 13 patients,four patients had SCA3/MJD(CAG) n expansion mutation(n = 65 ～ 74),nine patients had SCA7 allele expansion for 40 ～ 52 times.Patients with type 3 or 7 showed significant difference in nervous system injury.Conclusion The difference of clinical feature might be used in diagnosis of SCA3/MJD and SCA7,but genotype determination would be the only method of definite diagnosis.

Ethical dilemma and coping strategies of nurses involving in caring dying patients / 中华护理杂志

Objective To explore nurses' experiences of ethics dilemma and coping strategies involed in caring dying patients. Methods Interviews were conducted with 25 nurses from four different levels of hospitals in Shanghai. Results The ethical dilemmas that participants encountered with were derived from different standpoint and ethics decision-making between "relieve pain" and "extend life span","life value" and "insufficient medical resources","agent execution for patients' rights of being informed consent" and"medical intervention rights". Nurses' coping strategies included patiently communicating with family members to achieve agreement,failing to change family's decision then passively accepting it by self-adjustment,and following hospital rules and regulation or relying on team decision-making. Conclusion The study analyzed and discussed the reasons behind ethical dilemmas,as well as providing some suggestions on how to improve the coping abilities for nurse staffs. It can provide reference and basis for ethical decision-making.

Effect of different anesthesia methods on hemodynamics in gynecological laparoscopic operation / 中国基层医药

Objective To observe the effects of peridural and general anesthesia on haemodynamics in gynecological laparoscopic operation.Methods 106 patients with gynecological laparoscopic operation were randomly divided into epidural anesthesia group(n=53)and general anesthesia group(n=53)respectively.The changes of heart rate(HR),systolic blood pressure(SBP),diastolic blood pressure(DBP),SPO_2 were monitored before anesthesia,at 20min after pneumoperitoneum(pp),end of operation.Results The sober time in epidural anesthrsia geoup(7.1 ±2.5)min was significantly faster than that in general anesthesia group(20.8 ± 6.3)min(t=2.068,P＜0.05).At 20min after pp,HR in general anesthesia group(91 ±17)was significantly faster than that in ppidural anesthesia group before anesthesia(t=2.593,P＜0.05),and it was significantly higher than epidural anesthesia group(t=3.417,P＜0.05).SBP in epidural anesthesia group was singnificantly lower than before anesthesia(t=2.806,P＜0.05),and it was significantly lower than general anesthesia group(t=3.917,P＜0.05).Conclusion General anesthesia does not significantly better than epidural anesthesia in gynecological laparoscopic operation,but they should enhance the clinical monitoring of hemodynamics.

The changes of PECAM-1,Bcl-2 and Bax after focal cerebral ischemia in rats / 中国医师杂志

Objective To observe the changes of PECAM-1,Bcl-2 and Bax expressed by ischemic cerebrum of adult rats after focal cerebral ischemia. Methods Middle cerebral artery occlusion (MCAO) models were made by operation with Longa suture method in Wistar rats. The expression levels of PECAM-1,Bcl-2 and Bax at the 6th,12th,18th,24th,48th,72nd hour after MCAO were detected by immunohistochemistry staining. Results The expression levels of PECAM-1,Bcl-2 and Bax in cerebrum were significantly increased after MCAO. The expression levels of Bcl-2 we、re up to the peak at the 12th hour after MCAO, while the levels of Bax and PECAM-1 were up to the peak at the 24th and 48th hour after MCAO. At the 72nd hour after MCAO, the expression levels of PECAM.1.Bcl-2 and Bax were still higher than that in the control group(all P＜0.001).Conclusions PECAM-1,Bcl-2 and Bax participate in the different pathological stages of focal cerebral ischemia.

Study on risk factors of plasma hyperosmolality in severe stroke / 中华神经科杂志

100 g/d), hypernatremia and hyperglycemia were the three main risk factors resulting in plasma hyperosmolality. The 4-week survival rate of hyperosmolality group(47.1%) was significantly lower than that of non-hyperosmolality group(78.3%, P

Changes of expression of PECAM-1,P-selectin in activated platelet in patients with acute cerebral infarction / 中华神经科杂志

Objective To explore the changes of expression of platelet PECAM-1,P-selectin in patients with acute cerebral infarction.Methods The platelet expression levels of PECAM-1,P-selectin in 35 patients with acute cerebral infarction were serially measured with whole blood flow cytometry 24,48 hours and 5,7,14 days after the onset,and were compared with those of 30 normal controls.Results The platelet expression levels of PECAM-1 and P-selectin in patients with cerebral infarction 24 hours after the onset(78.35?10.48,7.75?3.04 respectively)were higher than those of controls(48.89?10.84,2.18?0.83 respectively,all P

Changes of CD31 and CD62p expressions in platelets of patients with acute cerebral infarction and its signification / 临床神经病学杂志

Objective To observe the changes of CD31 and CD62p expressions in platelets of patients with acute cerebral infarction(ACI) and its significance.Methods The expression levels of CD31 and CD62p of 53 patients with ACI were measured with whole blood flow cytometry within 48h after onset,and were compared with those of 38 patients with vascular risk factors(hypertension,diabetes,current smoking and hyperlipidemia) of cerebral infarction and 30 normal controls.Results The expression levels of CD31 and CD62p in patients with ACI [((90.91?)15.39)%,((7.00?)2.96)% respectively] were higher than those of patients with risk factors and normal controls(all(P

Inhibition of nuclear factor-?B attenuating graft reperfusion injury during liver transplantation / 第二军医大学学报

Objective:To investigate the protective effects of nuclear factor ?B inhibition on liver graft reperfusion injury during transplantation.Methods:Orthotopic liver transplantation using modified cuff technique was established in rats,animals were divided according to the grafts cold storaged in 4℃ Ringer's lactated solution with(PDTC group)or without 0.1 mol/L PDTC(control group)for 6 h.During the early stage of reperfusion,DNA binding activities of NF ?B in liver grafts were analyzed by EMSA(electrophoretic mobility shift assay),mRNA level of TNF ? and ICAM 1 by RT PCR,and activities of ALT and LDH were also detected.Results:NF ?B in liver grafts was activated at early stage of reperfusion during transplantation; PDTC treated liver displayed lower activation of NF ?B 1 h after reperfusion,whereas no difference was shown between 2 groups 6 h after reperfusion.Up regulation of TNF ? and ICAM 1 transcription,high level of ALT and LDH activities were observed in both groups during reperfusion,whereas the transcriptional up regulation and the activities of ALT and LDH in PDTC group were reduced compared with those of control group( P

Biological characters of hepatitis B virus transgenic mice strain C57-TgN(HBV adr2. 0)SMMU / 第二军医大学学报

Objective:To evaluate the biological characters of C57-TgN(HBV adr2.0)SMMU transgenic mice. Methods: Integration,expression,replication and histology change of hepatitis B virus gene in F6 transgenic mice were estimated by ge-nomic DNA PCR,Western blotting,ELISA,immunohistochemistry,serum DNA PCR,transmission electron microscopy and H-E staining. Results: Hepatitis B virus gene was integrated into F6 C57-TgN(HBV adr2. 0)SMMU transgenic mice and expressed HBsAg,HBcAg and X protein in liver tissue. HBsAg and HBeAg were expressed in serum of 19. 54% and 3. 39% F6 transgenic mice. Hepatitis B virus were replicated in serum and liver tissue of transgenic mice. Long-term integration,expression and replication of hepatitis B virus gene induced pathological lesion of transgenic mice liver and lung. Conclusion: C57-TgNCHBV adr2. 0)SMMU transgenic mice line has the biological characters including integration of hepatitis B virus gene into genomic DNA,expression and replication of hepatitis B virus gene in serum and liver, and histological change in liver and lung. It is a valuable animal system to study pathogenesis, treatment and prevention of hepatitis B virus.

Prevention of local recurrence of the breast cancer with intrao perative hot hypotonic solution soaking chemotherapy / 中国普通外科杂志

0.05). The rate of RCC after HHSSCT was 4.7% in study group; after second NS soaking, the rate of RCC was 19.1% in control group. The difference between the two groups was statistically significant (P