T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To explore the current status of the post competency evaluation index systems of Chinese general practitioners (GPs), and to summarize the post competency evaluation index systems of GPs in China.Methods:This study was a systematic review. We searched China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database (CQVIP), SinoMed, PubMed and other databases using "general practitioner" or "family doctor" or "standardized training for residents" or "post competency" or "evaluation system" or "core capability" or "assessment" or "evaluation" etc. as search terms and adding free words. The search was conducted from data establishment to October 2022. Literature screening and data extraction were carried out independently by 2 researchers using strict inclusion and exclusion criteria. The Ekman quality evaluation tool was used to evaluate the quality of the included literature. Excel was used to extract data information, including basic information of literatures, basic information of index systems and index content.Results:A total of 1 284 literatures were retrieved and 33 studies were included. A total of 15 research methods were used, and 28 (84.8%) applied 3 or more methods. There were 14 studies (42.4%) with good reliability and validity, and 17 studies (51.5%) with index weights. There were 12 applied theoretical bases, of which 20 studies (60.6%) used mature foreign competency models as a reference, 14 studies (42.4%) combined the job analysis and position requirements of GPs, and 11 studies (33.3%) interpreted policy documents. The content analysis method yielded 1 537 initial indicators, 1 268 indicators after eliminating repeated indicators, and 6 first-level indicators and 31 second-level indicators after combining and summarizing. Among the first-level indexes, "patient care" appeared most frequently (36.4% (462/1 268)); the secondary index with the highest frequency in this dimension was "master medical theoretical knowledge" followed by "community-oriented care ability" and "treatment and follow-up of common and frequently-occurring diseases"; the indicators "family-based care ability" and "human-centered care concept" reflected the characteristics of general medical practice. The frequency of "professional spirit and moral quality" (16.3%(207/1 268)), "clinical teaching and learning ability" (14.3%(181/1 268)) and "system-based practical ability"(11.1%(141/1 268)) ranked second, third and fourth among the first-level indicators respectively. The frequency of "basic public health service ability" (11.0%(139/1 268)) ranked the fifth, and the secondary indicator "health management of key community groups" reflected the concept of the whole life cycle of residents and the basic principle of continuity of care in general medicine. The frequency of "interpersonal and communication skills"(10.9%(138/1 268)) ranked sixth.Conclusions:There have been numerous researches on the post competency index evaluation system of GPs in China, but more research is still needed. There are many research methods with rich theoretical basis and Chinese characteristics. This study summarized the post competency evaluation index systems of GPs in China, generalized 6 first-level indicators and 31 second-level indicators that reflect the basic principles and characteristics of general medicine.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.
Humans ; Parkinson Disease/pathology* ; alpha-Synuclein/metabolism* ; Dopaminergic Neurons/metabolism* ; Pars Compacta/metabolism*

Objective:To survey the health literacy and related factors of family caregivers of patients with chronic diseases in Beijing.Methods:A survey was conducted from September to November 2018, among 1 350 family caregivers of patients with chronic diseases selected by stratified random sampling from 6 districts of Beijing. A self-filling questionnaire was used for the survey, which consisted of the basic information and health literacy of family caregivers. Health literacy included three parts: daily living habits, basic knowledge (knowledge of prevention and management of behavioral risk factors, knowledge related to chronic diseases and knowledge related to first aid) and chronic disease-related skills.Results:A total of 1 268 valid questionnaires were collected with a recovery rate of questionnaires was 93.9%. The median age of 1 268 family caregivers was 62 years (23-86) and 75.7% (960/1 268) were females. In terms of daily habits, smokers and drinkers accounted for 11.3% (143/1 268) and 21.5% (272/1 268) respectively; 82.7% (1 049/1 268) caregivers exercised regularly accounted, of whom 72.5% (761/1 049) exercised at least 4 times a week; 28.9% (366/1 268) caregivers had habit of light diet. In terms of basic knowledge of health literacy, 12.9% (163/1 268) of family caregivers mastered the basic knowledge (≥80% total score); family caregivers who were able to measure blood pressure, blood sugar, pulse, coping with hypoglycemia, cardiopulmonary resuscitation and dialing the emergency number correctly accounted for 27.4% (347/1 268), 18.1% (230/1 268), 15.1% (191/1 268), 15.7% (199/1 268), 6.0% (76/1 268) and 33.8% (429/1 268), respectively. For the six chronic disease-related skills, 23.7% (301/1 268) were able to call emergency number correctly and only 2.6% (33/1 268) were able to perform CPR. There were significant differences in the knowledge of behavioral risk factors ( χ 2=3.88, P=0.017), chronic disease related knowledge ( χ2=7.40, P=0.025), first-aid related knowledge ( χ2=12.04, P=0.002) and overall basic knowledge ( χ2=13.56, P=0.001) among family caregivers with different educational levels. There were significant differences in the knowledge of chronic diseases among family caregivers in different occupations ( χ2=8.78, P=0.012). Conclusion:The health literacy level of family caregivers of patients with chronic diseases in Beijing needs to be further improved, and there are differences in the health literacy of family caregivers with different educational qualifications and occupations.

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Objective:To summarize the clinical characteristics and risk factors of acute rejection(AR)of transplanted pancreas and kidney after simultaneous pancreas-kidney transplantation(SPK)and explore the effects of AR on the survival of transplanted pancreas, kidney and recipients.Methods:From September 2016 to July 2022, the relevant clinical data were retrospectively reviewed for 218 recipients undergoing SPK.According to whether or not AR occurred after SPK, they were assigned into two groups of AR(n=53)and non-AR(n=165). The relevant clinical data were compared for two groups of donors and recipients and the risk factors of AR analyzed by binary Logistic regression.Kaplan-Meier method was employed for comparing the survival rates of recipients/transplanted pancreas and kidneys in two groups.Results:A total of 53 cases(24.3%)developed ARs of transplanted pancreas(n=31, 14.2%)(5 of 2 ARs), transplanted kidney(n=15, 6.9%)(1 of 2 ARs)and transplanted pancreas & kidney AR(n=11, 5.0%)(2 of 2 ARs). Tacrolimus blood levels in AR and non-AR groups were(5.8±1.2)and(6.3±1.6)μg/L and failed to attain targets in 36(67.9%)and 78(47.3%)cases.During follow-ups, the incidence of pneumonia and urinary tract infections in AR group versus non-AR group were[43.4%(23/53)vs.27.3%(45/165)and 39.6%(21/53)vs.18.8%(31/165)]and the differences were statistically significant( P=0.028 & 0.002). The results of multifactorial regression analysis revealed that sub-optimal blood level of tacrolimus was an independent risk factor for an occurrence of AR in grafts of SPK recipients( OR=2.254, 95% CI: 1.167-4.353, P=0.016). Comparisons of 1/5-year postoperative survival rates between recipients in AR and no-AR group(98.1% vs.93.9% and 92.1% vs.92.4%)indicated that the differences were not statistically significant( P=0.233 & 0.806). Through comparing 1/5-year survival rates of transplanted pancreas in AR and non-AR groups(94.3% vs.100%, 89.4% vs.98.6%), the differences were statistically significant( P=0.003 & 0.004). And 1/5-year survival rates of transplanted kidneys in AR and non-AR groups(92.5% vs.100% and 90.2% vs.100%)were compared and the differences were statistically significant(all P<0.001). Conclusions:The incidence of AR is higher in transplanted pancreas and kidney after SPK.And the incidence of pneumonia and urinary tract infection is higher in AR group than that in non-AR group.Sub-optimal blood level of tacrolimus is an independent risk factor for the occurrence of AR.The 1/5-year survival rates of transplanted pancreas and transplanted kidney are lower in AR group than those in non-AR group.It has some effect on the survival of transplanted pancreas and kidney.

Objective:To investigate the effects of selegiline phosphate combined with liraglutide and osteopontin on glucolipid metabolism, bone mineral density and bone metabolism in patients with type 2 diabetes mellitus (T2DM) combined with osteoporosis (OP) .Methods:A prospective randomized controlled trial was designed.130 patients with T2DM combined with OP admitted to the outpatient clinic of Yantai Yantaishan Hospital from Jan.2020 to Aug. 2021 were selected as study subjects and pregrouped according to the pre-visit serial number according to the random number table method, 65 cases each. The control group weregiven liraglutide and osteopontin combination therapy, and the observation group were treated with sitagliptin phosphate combined with liraglutide and osteopontin, and both groups were treated continuously for 3 months. The tests compared the glycolipid metabolism [glycosylated hemoglobin (HAb1c) , triacylglycerol (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , 2h postprandial glucose (2hPG) , high-density and low-density lipoprotein cholesterol (HDL-C, LDL-C) ], bone density [4 sites of femoral trochanter, lumbar orthostyle, femoral neck, forearm], before and after 3 months of treatment in the 2 groups. Changes in bone metabolism (osteocalcin (OC) , type I collagen C-terminal peptide (S-CTX) , 25-hydroxyvitamin [25 (OH) D], type I procollagen amino-terminal peptidogen (PINP) , and bone-specific alkaline phosphatase (b-ALP) ] levels were detected, and the adverse effects and efficacy of drug administration in the 2 groups were compared.Results:After 3 months of treatment, FBG (7.48±1.02) mmol/L, TG (2.01±0.31) mmol/L, PINP (43.72±4.86) ng/ml, HAb1c (7.43±0.65) %, S-CTX (0.27±0.09) ng/ml, 2hPG (9.08±1.34) mmol/L in the observation group, LDL-C (2.58±0.27) mmol/L were lower than those in the control group (7.86±0.97) mmol/L, (2.29±0.34) mmol/L, (46.55±4.19) ng/ml, (7.81±0.62) %, (0.32±0.10) ng/ml, (10.52±1.41) mmol/L, (2.89±0.31) mmol/L ( t=2.177, 5.968, 3.556, 3.481, 2.996, 5.968, 6.080, P<0.05) ; after 3 months of treatment, the bone density of each site in the observation group was (0.76±0.09) g/cm 3, (0.75±0.10) g/cm 3, (0.76±0.11) g/cm 3, (0.75±0.09) g/cm 3 and OC (20.87±2.33) μg/L, b-ALP (19.70±2.35) U/L were higher than those of the control group (0.70±0.10) g/cm 3, (0.68±0.09) g/cm 3, (0.69±0.10) g/cm 3, (0.70±0.10) g/cm 3, (18.45±3.66) μg/L, (18.09±2.14) U/L ( t=3.596, 4.195, 3.796, 2.996, 4.497, 4.084, P<0.05) ; the overall efficiency of the observation group was 96.92%, higher than that of the control group 84.61% ( χ2=5.876, P<0.05) . The difference was not statistically significant when comparing the incidence of adverse reactions in the 2 groups ( χ2=0.000, P>0.05) . Conclusion:Sitagliptin phosphate combined with liraglutide and osteopontin can further improve clinical efficacy and regulate glucolipid metabolism in patients with T2DM combined with OP, and it also has an important role in improving bone density and regulating bone metabolism level in patients.

Objective:To survey the training needs for chronic diseases among family health care workers in Beijing.Methods:A questionnaire survey on training needs for chronic disease was conducted from September to November 2018 among 820 family health care workers from 15 community health service centers in Beijing selected by stratified random sampling. The questionnaire consisted of demographic information and training needs related to chronic diseases. The training needs included: the knowledge and skills related to chronic diseases: the types of chronic diseases expected to learn, the basic knowledge of chronic diseases (7 items), preventive health care knowledge (7 items), nursing and rehabilitation skills (9 items); the duration, frequency, method, time and location of training arrangement.Results:The survey showed that chronic disease that family health care workers most wanted to learn was hypertension (90.3%, 717/794); among the basic knowledge of chronic diseases, the highest need was disease risk factor (65.5%, 520/794); among the knowledge of preventive health care, the highest need was home safety protection (87.3%, 693/794); among nursing and rehabilitation skills, the highest need was blood glucose measurement (83.1%, 660/794). The female respondents had higher training need for basic knowledge of chronic diseases than males ( Z=2.51, P=0.012). There were significant differences in the needs for preventive health care knowledge among respondents of different gender ( Z=2.72, P=0.007), occupation ( H=15.02, P=0.001) and educational level ( H=12.01, P=0.002). Respondents with different age ( H=6.49, P=0.039), occupation ( H=52.93, P<0.001) and educational level ( H=9.56, P=0.008)) had different needs for nursing and rehabilitation skills. Among the respondents, 58.2% (462/794) indicated that duration of each course should be 30-59 min, 34.0% (270/794) wanted to participate in the training once a month, 53.1% (422/794) wanted to participate in the training in the form of large class, 39.2% (311/794) were willing to participate in the training on working days and 48.7% (387/794) wanted to be trained in community health service institutions. Conclusions:There are diverse training needs of family health care workers. Attention should be paid to the implementation of need-oriented training. It is crucial to promote the motivation of family health care workers to participate in the training, which can improve the training effect and facilitate their role in family health management.

Objective:To investigate the status quo of potentially inappropriate medication (PIM) among elderly hypertensive patients in community general practice clinic and related influencing factors.Methods:A total of 767 prescriptions for elderly hypertensive patients in a community health service center in Beijing from October 2020 to August 2021 were reviewed. The prevalence of PIM was assessed based on the criteria of potentially inappropriate medications for older adults in China(2017). Logistic regression analysis was employed to analyze the influencing factors for PIM. Results:The survey showed that 198 elderly patients had PIM with 244 person-doses. The top three drugs with high rate of PIM were benzodiazepine-estazolam (64 person-doses), clopidogrel (53 person-doses) and insulin (35 person-doses). Univariate analysis showed that PIM was significantly associated with types of medication;and underlying diseases hypertension with hyperlipidemia, coronary heart disease, type 2 diabetes, osteoarthritis, upper respiratory tract infection and insomnia (χ 2=82.58, 13.65, 17.74, 7.52, 10.34, 68.19,respectively,all P<0.05). Multivariate logistic regression analysis showed that the types of medication, hypertension complicated with upper respiratory tract infection, and insomnia were independent influencing factors for PIM ( OR=1.55, 2.47, 9.05; P<0.05). Conclusion:The study shows that PIM is more common in elderly hypertensive patients in community general practice clinics,which is associated with types of medication, hypertension complicated with upper respiratory tract infection and insomnia. It is suggested that general practitioner working in community clinics should be aware of PIM, minimize the number of prescription drugs, and choose new drugs or non-drug treatments to reduce the occurrence of PIM.