Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

Objective·To explore the correlation between serum small ubiquitin-like modifier 1(SUMO1)levels and hypertriglyceridemia in patients with type 2 diabetes mellitus(T2DM).Methods·A total of 239 newly diagnosed T2DM patients were recruited from the endocrinology clinic of Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,between September 2020 and March 2021.Among them,92 patients had hypertriglyceridemia,and 147 patients did not.Basic information and laboratory parameters were collected.The differences in serum SUMO1 levels between the two groups were analyzed.Factors influencing hypertriglyceridemia in patients with T2DM were analyzed,and the impact of serum SUMO1 levels on the risk of hypertriglyceridemia in T2DM patients was investigated.Results·Patients with T2DM and hypertriglyceridemia had significantly higher serum SUMO1 levels compared to those without hypertriglyceridemia(1 114.99 pg/mL vs 902.43 pg/mL,P＜0.001).Binary Logistic regression analysis suggested that serum SUMO1 levels(OR=1.527,95%CI 1.200?1.943),glycated hemoglobin(OR=1.202,95%CI 1.038 ? 1.391),and blood uric acid(OR=1.006,95%CI 1.003 ? 1.010)were independent risk factors for hypertriglyceridemia in patients with T2DM.After adjusting for various confounding factors and stratifying serum SUMO1 levels into quartiles,the risk of hypertriglyceridemia in T2DM patients with the highest quartile(Q4)of serum SUMO1 levels was 2.707 times higher compared to those in the lowest quartile(Q1)(95%CI 1.231?5.951).Multiple linear stepwise regression analysis revealed that female gender,waist-to-hip ratio,triglycerides and serum creatinine were independent risk factors for elevated serum SUMO1 levels.Conclusion·Serum SUMO1 level in patients with T2DM complicated with HTG is significantly higher than that in patients without HTG,and the serum SUMO1 level is an independent risk factor for T2DM complicated with HTG.

TCM dispensing is the most basic clinical pharmaceutical work of TCM.In recent years,based on the 9 key technologies of TCM dispensing,the TCM dispensing industry has ushered in great development,and innovative TCM dispensing information system and intelligent dispensing equipment have appeared.This article sorted out the current situation of TCM dispensing industry and looked forward to its future development route.The results showed that the introduction of new technology and new equipment in the key technical links of procurement acceptance,dispensing review,TCM decocting,medication guidance and so on have improved the quality of dispensing service and ensured the quality and safety of medication.In the development of modern TCM dispensing industry,it is necessary to improve the quality control standard system,service standard system and core equipment standard system in the standardization of dispensing technology;in terms of talent cultivation in the field of dispensing,it is necessary to focus on restructuring and building new educational models to cultivate new medical talents that intersect medical and engineering fields;in terms of informatization and intelligence,it is necessary to develop intelligent equipment that is more in line with the characteristics of TCM,and further promote and improve the"shared TCM pharmacy"model.Through improving the content of TCM clinical pharmaceutical care,developing new technology and equipment of TCM dispensing,and improving the level of dispensing service and education,it is expected to gradually realize the standardization,informatization and intelligent development of modern TCM dispensing industry.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*

Objective: To observe the association between puberty development and thyroid function among school-aged girls in Minhang District of Shanghai, in order to explore the effect of puberty development on thyroid function. Methods: The study was based on a cohort of adolescent girls recruited in iodine-suitable areas of Minhang District, and the baseline and follow-up survey have been carried out from January to March 2019. The method of phased cluster sampling was used to select one junior high school in the east, south, north and middle of Minhang District, Shanghai, respectively. Finally, 464 new junior high school girls were included in the Cohort study for physical examination, and girls were followed up from January to March 2021. The Puberty Development Scale (PDS) was used to assess the stage of puberty. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were determined for each participant. Thyroid homeostasis structure parameters (THSPs) was calculated. Changes of Thyroid hormones at baseline and follow-up were compared by Wilcoxon signed rank sum test. Multiple linear regression analyses were used to evaluate the associations of thyroid hormones (THs) and THSPs changes with pubertal develepment. Results: Serum TSH levels of female studentds decreased significantly, while their FT3 and FT4 levels increased significantly during the study period ( Z=-10.53, -4.71, -12.46, P <0.01). In multiple linear regression analysis after adjustment for co-variables (including baseline age, change of BMI and waist circumference), FT4 and thyroid feedback quantile-based index (TFQI) in the higher puberty category scores changes (△PCS) group were further reduced compared with those in the low △PCS group ( β =-0.66, -0.55 ). Compared to the late puberty at baseline and follow-up (BLFL) group, FT4 and TFQI showed higher decline in the pre-puberty at baseline and late puberty at follow-up (BPFL) group with the pre-puberty at baseline and end of puberty at follow-up (BPFT) group ( β =-0.55, -0.44)( P <0.05). There were no association of △TSH, △FT3, △FT4/FT3 and TSH index changes (△TSHI) with △PCS or the puberty pattern. Conclusion Serum TSH decreases while serum FT3 and FT4 increase among girls during puberty. Both the initial stage and the velocity of pubertal development are related to thyroid hormone fluctuations.

ObjectiveTo develop basic training courses for family doctor teams for people with disabilities. MethodsUtilizing the methods and theories of the World Health Organization (WHO) rehabilitation competency framework (RCF), and referring to the WHO universal health coverage global competency framework, the rehabilitation competency characteristics of family doctor teams for people with disabilities in community settings were analyzed, and a basic training course system for these teams based on the RCF was developed. Results and ConclusionBased on RCF, a competency framework for family doctor teams serving people with disabilities has been constructed. The objectives, content and training course system for basic rehabilitation training has been established.

Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS) is a thrombotic microvascular disease caused by streptococcus pneumoniae infection, which is one of the causes renal failure in children.Clinical manifestations include thrombocytopenia, hemolytic anemia and acute renal failure.The neuraminidase and surface protein C substance of Streptococcus pneumoniae, immune factors and complement play important roles in the pathogenesis of SP-HUS.The complement inhibitors provides a new solution for the treatment of SP-HUS.However, few SP-HUS cases have been reported in China.This paper reviews the pathogenesis, clinical manifestations and treatment of SP-HUS to help clinicians better understand the disease, early recognition and intervention treatment.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.