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 retail milk tea industry is in a period of rapid development, but there is little research on its nutrient content, which restricts the nutritional guidance of milk tea. Objective To determine the levels of nutrients in best-selling handcrafted milk tea in Shanghai and analyze the nutritional characteristics. Methods In 2018 and 2021, a total of 13 handcrafted milk tea brands with ≥3 branch stores in Shanghai were selected by searching for milk tea on Meituan and Ele.me food delivery platforms, and a total of 122 types of handcrafted milk tea products were collected from the top three sales [milk tea (including all sweetness levels available), milk cover tea, and fruit tea]. National standard methods were used to detect energy, protein, fat, carbohydrate, sugar, trans fatty acid, calcium, caffeine, and tea polyphenol. Results The median energy of the milk tea samples was 310 kJ (per 100 g sample). The main sources of energy were carbohydrate and fat. The levels of energy, protein, and fat in milk cover tea and milk tea were significantly higher than those in fruit tea (P＜0.05), and there was no significant difference in carbohydrate among them. The total sugar, fructose, and glucose levels in milk tea were significantly lower than those in milk cover tea and fruit tea, and the lactose level in fruit tea was significantly lower than those in milk tea and milk cover tea (P＜0.05). Themedian trans fat acid level in milk cover tea was higher than that in milk tea (P＜0.05). The median levels of caffeine and tea polyphenol were higher in milk tea than in milk cover tea (P＜0.05). The levels of energy, carbohydrate, sucrose, total sugar, and calcium in milk tea were positively correlated with the number of ingredients added (0-3) (r=0.386, 0.371, 0.238, 0.698, 0.466, respectively, P < 0.05). The levels of energy, carbohydrate, and total sugar tended to increase with increasing sweetness (P<0.05), and total sugar was mainly sucrose, followed by fructose and glucose. The total sugar levels of the samples labeled sugar free, light sugar, half sugar, less sugar, and regular sugar were 3.40 (2.20, 4.9), 4.97 (4.25, 5.97), 5.80 (4.31, 6.88), 6.59 (5.17, 8.53), and 7.96 (6.82, 9.20) g, respectively; the proportions of the samples containing more than 0.5 g of total sugar were 93.3% for sugar free milk tea, 47.4% for light sugar milk tea, and 94.0% for regular sugar milk tea; the proportion of the regular sugar samples with sugar content greater than 10 g was 18.0% (all samples with nominal sugar content were measured per 100 g). Conclusion The retail handcrafted milk tea in Shanghai is characterized by high energy, high added sugar, high fat, and low protein. It is necessary to standardize the added sugar content and sweetness labeling, strengthen the nutrition education of milk tea, and guide residents to limit its intake.

Background Children and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. Objective To investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. Methods Data were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d⁻¹) and the low-frequency (≤1 time·week⁻¹) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. Results A total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d⁻¹ than in those who consumed ≤1 time·week⁻¹. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d⁻¹ had a higher total cholesterol (difference=0.20 mmol·L⁻¹, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L⁻¹, P=0.010) than those who consumed ≤1 time·week⁻¹; boys in grades 6-9 who consumed SSBs ≥1 time·d⁻¹ had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L⁻¹, P=0.039) than those who consumed ≤1 time·week⁻¹. Conclusion High-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children.

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.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

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.