Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation.Methods:Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups ( n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results:Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS ( P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased( P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions:Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.

Objective:To conduct a scoping review of studies on the needs assessment based on decision needs assessment workbook and to provide a reference for conducting related studies in China.Methods:Using the scoping review guidelines of Joanna Briggs Institute in Australia as a methodological framework, PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang, VIP and China Biology Medicine disc were searched from establishment of the databases to March 31, 2023.Results:A total of 12 studies were included and the basic information, study objective, type of study, participants, collection method, evaluation guidance tools and results of the included literature were summarized and analyzed.Conclusions:In the future, when medical staff use workbooks for needs assessment, they should pay attention to fully incorporating the core elements of the workbooks, evaluating the decision-making needs of patients from multiple perspectives such as spouses and peer helper, and developing or utilizing existing patient decision aids to provide decision support for patients based on the results of needs assessment, thereby improving the quality of shared decision-making.

Objective:To explore the feasibility of expectant management in pregnant women with preterm premature rupture of membranes (PPROM) before 28 weeks of gestation.Methods:A retrospective analysis was conducted on the clinical data of 92 pregnant women diagnosed with PPROM before 28 weeks and delivered in Peking University First Hospital from January 2015 to March 2023. These women were divided into the termination group or expectant management group, and the latter was further divided based on whether the rupture of membranes occurred before 24 weeks or after. Clinical data of the women and neonates between the two groups and the two subgroups were analyzed. Additionally, all the subjects were divided based on the presence or absence of severe neonatal complications and clinical data of the mothers and their neonates were also analyzed. Statistical analyses were performed using t-tests, Mann-Whitney U tests, Chi-square tests, or Fisher's exact tests. Results:(1) Among the 92 women with PPROM, 53 (57.6%) chose to terminate the pregnancy, while 39 (42.4%) chose expectant management including ten twins and 29 singletons. (2) Compared to the termination group, the expectant management group had a smaller percentage of multiparous women [7.7% (3/39) vs. 32.1% (17/53), Fisher's exact test, P=0.019], greater gestational age at membrane rupture [24 +6 weeks (18-27 +6) weeks vs.21 +3weeks (14 +2-27 weeks), Z=53.14, P=0.042], and a lower incidence of oligohydramnios after membrane rupture [46.2% (18/39) vs. 84.9% (45/53), χ2=6.56, P=0.031]. (3) All of the 39 women in the expectant group gave birth before 37 weeks with the mean gestational age at delivery of 28 +1weeks (25 +1-36 +1 weeks) and 49 live born babies, among which four neonates died giving the survival rate of 91.8%(45/49). There were no statistically significant differences in gestational age at delivery or neonatal outcomes between women with membrane rupture before 24 weeks and those ruptured between 24 and 27 weeks and 6 days of gestation (all P>0.05), but the expectant duration was significantly longer in the former group [55.0 d (20.0-96.0 d) vs. 9.0 d (0.5-52.0 d ), Z=－4.95, P<0.001]. (4) The 49 neonates were further divided into with ( n=9, including the death) or without ( n=40) severe complication subgroups. Those neonates in the non-severe complication subgroup had a significantly greater gestational age at birth compared to those in the other subgroup [30 +6 weeks (27 +5-36 +4 weeks) vs. 27 +5 weeks (25 +1-31 +5 weeks), Z=－3.42, P=0.001], a longer expectant duration [42.0 d (3.0-80.0 d) vs. 19.0 d (0.5-59.0 d), Z=－2.31, P=0.021], a higher birth weight [(1 630±544) g vs. (1 069±272) g, t=4.56, P=0.009], a lower incidence of neonatal asphyxia [2/9 vs. 70.0% (28/40), Fisher's exact test, P=0.012], a shorter hospital stay [37.5 d (3.0-54.0 d) vs. 67.0 d (60.0-105.0 d), Z=－3.01, P=0.003] and a higher proportion of pregnancies completing two courses of fetal lung maturation [5/9 vs. 17.5% (7/40), Fisher's exact test, P=0.029]. (5) Among the ten twin pregnancies, all the 20 babies developed severe complication resulting a higher proportion of twins in the severe complication group than in the non-severe complication group [50% (20/40) vs. 0/9, Fisher's exact test, P=0.005]. Conclusions:For pregnant women with PPROM before 28 weeks, under the premise of informed consent and thorough evaluation, expectant management can be considered if there are no indications for immediate termination of pregnancy, to achieve a higher neonatal survival rate. However, the incidence of severe complications related to preterm infants remains high in the short term, with most having a good prognosis after treatment in the neonatal intensive care unit. Twin pregnancies and lower gestational age at birth are risk factors for severe complications in preterm infants.

BACKGROUND: The phenotype maintenance of diced cartilage is a very important factor to reduce cartilage absorption rate in augmentation rhinoplasty. A novel method which combined diced cartilage with chondrocyte spheroids in gelatin methacrylate (GelMA) hydrogel may have potentially good performance in phenotype maintenance, and is worth exploring. METHODS: The complex grafts formed by loading diced cartilage with chondrocyte spheroids into GelMA hydrogel were used as the experimental group, and the grafts formed of diced cartilage in GelMA were used as the control group.The two groups of grafts were implanted subcutaneously in nude mice. After 1 month and 3 months, the grafts were taken for general observation and histological analysis. The diameter changes of cartilage, the nuclei loss of chondrocyte, and glycosaminoglycan secretion were analyzed. RESULTS: Chondrocyte spheroids with obvious proliferation can be seen in the experimental group. Some diced cartilages had become a whole through the interconnection of chondrocyte spheroids. In addition, the diameter of the chondrocyte spheroids—diced cartilage complex in the experimental group increased significantly, and its nuclei loss rate was less than 1/2 of that in the control group. The maintenance of proteoglycans in diced cartilages in the experimental group was significantly better than that in the control group. CONCLUSION The combination of diced cartilage with chondrocyte spheroids in GelMA hydrogel can significantly reduce the absorption of cartilage extracellular matrix, enhance phenotype maintenance during subcutaneous ectopic implantation, and can produce inter-chondral connections.

ObjectiveTo evaluate the changes of the usage of oil， salt， sugar and nutritional knowledge and behavior intervention among diners before and after the establishment of healthy canteens and restaurants in Shanghai. MethodsA comprehensive intervention was conducted through the establishment of healthy canteens and restaurants， encompassing interventions such as oil， salt， and sugar management， improvement of nutritional environment， staffing and training activities， and nutrition labeling guidance. A pre-post self-controlled study design was used to compare changes in oil， salt and sugar usage， as well as diners’ knowledge and behaviors related to nutrition and nutrition labeling， before and after the intervention. ResultsAfter intervention， the total usage of oil， salt， and sugar per meal in the canteens and restaurants decreased by 18.33%， 14.83%， and 13.66%， respectively，and all had statistically significance differences（P<0.001）. The awareness rate of "cooking oil intake"， "salt intake"， and "added sugar intake" among diners increased from 24.07% to 38.04%， 58.52% to 71.28%， and 26.85% to 45.01%， respectively. The awareness rate of "daily food types" and "weekly food types" increased from 43.07% to 56.53% and 49.52% to 64.32%， with significant differences （P<0.001）. The rate of understanding the content of nutrition labels increased from 66.91% to 76.90%， the awareness rate of nutrition labels increased from 53.59% to 69.06%， the rate of active reading of nutrition labels among diners increased from 73.38% to 81.23%， and the rate of selecting and purchasing food based on the information of nutrition labels increased from 69.27% to 77.79%， all of which were statistically significant （P<0.001）. ConclusionThe comprehensive interventions carried out through the creation of healthy canteens and restaurants have significantly impact on usage of oil， salt， and sugar， as well as on the nutritional knowledge and behaviors of diners.

Purpose: Anxiety, depression, and poor quality of life (QOL) were considered important concerns that hindered the rehabilitation of breast cancer survivors. A number of studies have investigated the effects of physical activity, but they have not reached the same conclusions. This review aimed to identify the effects of physical activity on QOL, anxiety, and depression in breast cancer survivors. Methods: PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, SinoMed, CNKI, Vip, and WanFang databases were searched for the time period between January 1, 2012, and April 30, 2022. Studies were included if they were randomized controlled trials of the effects of physical activity on QOL, anxiety, or depression in breast cancer survivors. The tools of the Joanna Briggs Institute were used to assess the quality of the included studies. R software version 4.3.1 was used for meta-analysis. Results: A total of 26 studies, involving 2105 participants, were included in the systematic review. Among these, 20 studies involving 1228 participants were included in the meta-analysis. Compared with the control group, the results indicated that physical activity can significantly improve QOL(Hedges' g = 0.67; 95% CI 0.41–0.92) and reduce anxiety (Hedges' g = −0.28; 95% CI −0.46 to −0.10) in breast cancer survivors. However, the effect of physical activity on depression (Hedges' g = −0.46; 95% CI −0.99 to 0.06) was not statistically significant. Conclusions Physical activity was an effective intervention to improve QOL and reduce anxiety in breast cancer survivors, as well as showed positive trends in depression, although without statistical significance. More well-designed studies are required to clarify the effects of different types of physical activities on the QOL, anxiety, and depression among breast cancer survivors.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Esophagogastric variceal bleeding (EGVB) is one of the main complications of decompensated portal hypertension, especially in patients with liver cirrhosis, and it often has a high mortality rate. Medication combined with endoscopy is the main prevention and treatment method for EGVB, while transjugular intrahepatic portosystemic shunt (TIPS) combined with variceal embolization can also be selected for some high-risk patients, and individualized diagnosis and treatment of portal hypertension based on hepatic venous pressure gradient should become the latest consensus and the main strategy. This article mainly reviews endoscopic therapy and TIPS for the prevention and treatment of EGVB patients with decompensated portal hypertension in terms of selection of indications, incidence rate of complications, and respective advantages and disadvantages.

Small cell lung cancer (SCLC) is a rapidly developing malignant tumor, which is highly heterogeneous and prone to drug resistance, and the prognosis is usually poor. Poly ADP-ribose polymerase (PARP) inhibitors target the DNA damage response pathway, preventing DNA repair, thereby exerting anti-tumor effects. Currently, PARP inhibitors are used as monotherapy or in combination with DNA-damaging agents or immune checkpoint inhibitors in the treatment of SCLC. Although the current research results are limited, it can be seen that PARP inhibitors may be a breakthrough in the targeted therapy of SCLC.