Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

ObjectiveTo investigate the mental health of pediatricians in Guangzhou and its influencing factors， and to provide countermeasures for improving the mental health of pediatricians. MethodsA stratified random sampling method was used to randomly select 400 pediatricians in 11 districts of Guangzhou， and they were surveyed using the Symptom Check List（SCL-90） and the Job Stressor Scale. ResultsThe top three job stressors scored by pediatricians in Guangzhou were external environment （3.23±0.59）， workload （3.19±0.56）， and organizational management （2.74±0.55）. All factor scores were higher than those of the clinician group except for career interest， and the difference was statistically significant （P<0.01）. The number of pediatricians with mental health problems was 109， accounting for 27.25%. All factor scores were higher than the physician norm except for anxiety and paranoia. The correlations between each factor of work stressors and each factor of SCL-90 were positive and statistically significant （P<0.05）， except for two pairs of factors， workload and terror as well as external environment and terror. The results of univariate analysis showed statistically significant differences in the mental health scores of pediatricians with different health status， years of work experience， job satisfaction， job stress， and career prospects （P<0.05）. The results of multiple linear regression showed that health status， years of work experience， professional interest， interpersonal relationship， and doctor-patient relationship were influential factors in the mental health of pediatricians （P<0.05）. ConclusionThe mental health of pediatricians in Guangzhou is unsatisfactory， and the factors affecting them are mainly external objective factors such as workload and organizational management.

Objective:To automatically synthesize Al 18F-fibroblast activation protein inhibitor (FAPI)-74, and explore its value of clinical application. Methods:Al 18F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100, and its yield, radiochemical purity and stability were determined. Sixteen normal Kunming (KM) mice were randomly divided into 4 groups and euthanized at 10, 30, 60 and 90 min after Al 18F-FAPI-74 injection, and the biodistribution was measured. MicroPET/CT dynamic scanning (60 min) was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake. Al 18F-FAPI-74 PET/CT imaging was performed on 3 volunteers (1 male, 2 females; age: 37, 41, 43 years) to evaluate the clinical application value of Al 18F-FAPI-74. Results:The automated synthesis time of Al 18F-FAPI-74 was about 35 min, with the synthesis yield of (21.34±3.86)% (without attenuation correction, n=5) and the radiochemical purity more than 99%. The radiochemical purity was still more than 96% after placement at 37 ℃ for 6 h. Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder, and the tumor uptake was the highest at 20 min, and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min. PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium, most organs such as the liver and lung had background uptake, and the maximum SUV max of persistent high uptake of tumor was 17.08. Conclusions:Al 18F-FAPI-74 has the advantages of simple synthesis, high yield, stable quality and good imaging performance in mice and volunteers. It is a kind of imaging agent that meets the requirements of clinical diagnosis.

Cerebrovascular diseases have the characteristics of high morbidity, high disability, high mortality and high recurrence rate, which seriously harm human health and increase the national health economic burden. 3-n-Butylphthalide (NBP) is a new drug commonly used in clinical treatment of cerebrovascular diseases, and it is also one of the main active components in traditional Chinese medicine such as Angelica sinensis and Chuanxiong. In this review, the pharmacological effects of NBP were systematically summarized. Studies have shown that NBP has pharmacological effects such as antiplatelet aggregation, anti-thrombosis, inhibiting neuronal apoptosis, anti-oxidation, anti-cerebral ischemia, anti-brain injury, and anti-vascular dementia. In clinical practice, it is often combined with edaravone, alteplase, fasudil, Xingnaojing injection, and compound Danshen injection to treat cerebral vascular diseases such as stroke, vascular dementia, and cerebral vasospasm, and plays a good synergistic effect. This summary could provide support for the rational clinical application of NBP, and also provide basis for the in-depth study of the interaction of its drug combination.

OBJECTIVE: To observe the effect of electroacupuncture (EA) on protein expressions of suppressor of cytokine signaling 3 (SOCS3) and insulin receptor substrate-1 (IRS-1) in hypothalamus and morphology of pancreas islet in Zucker diabetic fatty (ZDF) rats, and to explore its possible mechanism on improving plasma glucose and insulin resistance of type 2 diabetes mellitus (T2DM). METHODS: Twelve SPF male ZDF rats were selected and fed with high-fat diet for 4 weeks to establish the T2DM model, after modeling, the rats were randomly divided into a model group and an EA group, 6 rats in each one. Besides, 6 SPF male Zucker lean rats were selected as a blank group. In the EA group, EA was applied at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, 2 mA in intensity, once a day, 20 min each time, 6 times a week for 4 weeks. The fasting plasma glucose (FPG) was measured before and after intervention. The serum level of fasting insulin (FINS) was measured by radioimmunoassay, and the homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated; the morphological change of pancreas islets was observed by HE staining; the protein expressions of SOCS3 and IRS-1 in hypothalamus were detected by Western blot. RESULTS: Before intervention, compared with the blank group, FPG in the model group and the EA group was increased (P<0.01). After intervention, compared with the blank group, FPG, serum level of FINS and HOMA-IR were increased (P<0.01), the protein expression of SOCS3 was increased while IRS-1 was decreased in the hypothalamus in the model group (P<0.01). Compared with the model group, FPG, serum level of FINS and HOMA-IR were decreased (P<0.01), the protein expression of SOCS3 was decreased while IRS-1 was increased in the hypothalamus in the EA group (P<0.01). In the model group, the shape of pancreas islets was irregular, the area of pancreas islets and the number of islet β cell nuclei were decreased, the nuclei of islet β cell was compensatory enlargement. In the EA group, the shape and the area of pancreas islets and the number of islet β cell nuclei were improved, the compensatory increase of islet β cell nuclei was alleviated compared with the model group. CONCLUSION Electroacupuncture can reduce the fasting plasma glucose, improve the morphology of pancreas islets, and alleviate the insulin resistance in ZDF rats. The mechanism may relate to the down-regulation of SOCS3 and up-regulation of IRS-1 in the hypothalamus, and improving the function of hypothalamus in regulating peripheral glucose metabolism.
Acupuncture Points ; Animals ; Blood Glucose/metabolism* ; Diabetes Mellitus, Type 2/therapy* ; Electroacupuncture ; Hypothalamus/metabolism* ; Insulin Receptor Substrate Proteins/metabolism* ; Insulin Resistance ; Male ; Pancreas/metabolism* ; Rats ; Rats, Zucker ; Suppressor of Cytokine Signaling 3 Protein/metabolism*

OBJECTIVE: To analyze the clinical features of acute myeloid leukemia (AML)/high-risk myelodysplastic syndrome (MDS) patients aged over 60 years old. METHODS: The clinical data of 61 elderly newly diagnosed patients with AML and high-risk MDS who submitted to the Department of Hematology/Oncology of the First Affiliated Hospital of Tsinghua University from January 2009 to April 16, 2021 were retrospectively analyzed. These patients were divided into chemotherapy group (45 cases) and supportive treatment group (16 cases). The overall survival (OS) was analyzed by Kaplan-Meier method, and the prognostic factors of survival were analyzed by multivariate Cox regression. RESULTS: After 2 cycles of induction chemotherapy, the complete remission (CR) rate was 37.8% (17/45), and overall response rate was 62.2% (28/45) in the chemotherapy group. The median OS in the chemotherapy group and supportive treatment group was 11.3 (0.07-43) and 1.6 (0.33-7.72) months, respectively (P<0.001). The median OS in patients who reached CR or did not reach after 1 cycle of induction chemotherapy was 19.8 (10-30.63) and 8.17 (0.07-43) months, respectively (P<0.05), while after 2 cycles was 22.7 (4.2-43) and 7.26 (0.07-26) months, respectively (P<0.001). Univariate analysis showed that age > 80 years old, CCI score > 2, PS score > 2 and supportive treatment were the adverse prognostic factors for OS. Further multivariate analysis suggested that chemotherapy was the only independent prognostic factor for OS (HR=0.140, 95%CI: 0.048-0.409, P<0.001). In the chemotherapy group, univariate analysis showed that CCI score > 2 and failure to reach CR after induction chemotherapy were poor prognostic factors. Multivariate analysis showed that CCI score > 2 (HR=0.139, 95%CI: 0.050-0.384, P<0.001) and failure to achieve CR after induction chemotherapy (HR=0.103, 95%CI: 0.041-0.259, P<0.001) were the adverse prognostic factors for OS. The patients were tolerant to side-effect of chemotherapy. CONCLUSION Appropriate chemotherapy can prolong the survival of elderly patients with AML and high-risk MDS.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVE: To evaluate the effects of auricular acupoint bloodletting (AB) and auricular acupressure (AA) on sleep quality and the levels of melatonin (MT), glutamic acid (Glu), and γ -aminobutyric acid (GABA) in college students with primary insomnia, and to explore the possible mechanism. METHODS: Totally 74 college students at Hebei University of Chinese Medicine with primary insomnia were selected from October 2019 to October 2020. All patients were assigned to AB+AA group (37 cases, received combination of AB and AA) and AA group (37 cases, received only AA on the same acupoints) by a random number table. Each group was treated twice a week for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI) score, Chinese medicine (CM) syndrome score, total effective rate, serum concentrations of MT, Glu, and GABA, and Glu/GABA ratio were compared between the two groups after treatment and at follow-up. The safety of therapy was also evaluated. RESULTS: After 4-week treatment, the total scores of PSQI, each PSQI component score, and the CM syndrome scores in both groups all decreased (P<0.05); the serum MT concentrations in both groups all increased (P<0.05). The concentrations of Glu and GABA in the AB+AA group were significantly higher than those in the AA group after treatment (P<0.05). However, there was no significant difference in the ratio of Glu/GABA in both groups before and after treatment (P>0.05). At follow-up, the CM syndrome score in the AB+AA group was significantly lower than that in the AA group (P<0.05). There was no significant difference between the two groups in total effective rates and adverse events (P>0.05). CONCLUSIONS Both AB+AA and AA can relieve insomnia symptoms, but a stronger long-term effect were observed for AB+AA. AB+AA can promote the secretion of MT, increase the levels of Glu and GABA more effective than AA, and regulate their imbalance, and thus it may be benificial for treating insomnia.
Humans ; Acupressure ; Acupuncture Points ; Bloodletting ; Sleep Initiation and Maintenance Disorders/therapy* ; Sleep Quality ; Syndrome ; Students ; gamma-Aminobutyric Acid

Objective （ ） To explore the feasibility of using generalized estimating equation GEE to analyze the influencing - （ ） factors of high frequency hearing loss HFHL among noise exposed workers in an air conditioner manufacturing enterprise. Methods - The noise exposed workers in an air conditioner manufacturing industry who had been tested for pure tone hearing threshold twice or more from 2015 to 2019 were selected as the research subjects using the judgment sampling method. Data ， ， ， ， ， （ ） such as age length of service gender smoking alcohol consumption body mass index BMI and HFHL were collected. The Results influencing factors of HFHL were analyzed using the GEE. The detection rates of HFHL from 2015 to 2019 were ， ， ， ， ， 22.2% 23.8% 24.2% 24.1% and 20.9% respectively. Among them the detection rate of HFHL in 2019 was lower than that （ P ） ， ， in 2017 and 2018 all <0.001 . The GEE analysis results showed that the risks of HFHL in 2015 2016 2017 and 2018 were （ P ）， higher than that in 2019 all <0.01 regardless of interaction effects and after adjusting for confounding factors such as ， ［OR（ CI）］ （ - duration of noise exposure smoking and BMI. The odds ratios and 95% confidence intervals 95% were 1.19 1.07 ）， （ - ）， （ - ） （ - ）， 1.33 1.26 1.13 1.39 1.30 1.18 1.43 and 1.27 1.15 1.39 respectively. The risk of HFHL was higher in males than in （P ）， OR（ CI） （ - ） ， （P ）， OR females <0.01 and 95% was 3.78 3.00 4.77 . The older the age the higher the risk of HFHL <0.01 and （ CI） （ - ） Conclusion - 95% was 1.07 1.05 1.09 . The influencing factors of HFHL among noise exposed workers in the air conditioner industry are age and gender. GEE can be used to analyze the factors influencing the longitudinal data of HFHL in workers with noise exposure.

Objective: Cerebrovascular disease can be roughly divided into 2 subtypes: Cerebral ischemia (CI) and cerebral hemorrhage (CH). No scale currently exist that can predict the subtypes of cerebrovascular diseases. This study aims to establish a prediction scale for the subtypes of cerebrovascular diseases. Methods:A total of 1200 cerebrovascular disease patients were included in this study, data from 1081 (90％) patients were used to establish the CI-CH risk scale, and data from 119 (10％) patients were used to test it. Risk factors for the CI-CH risk scale were identified by 2 screens, with two-tailed student ' s t-test and two-tailed Fisher ' s exact test preliminarily and with logistic regression analysis further. The scores of each risk factor for CI-CH risk scale were determined according to the odds rate, and the cut-off point was determined by Youden index. Results: Nine risk factors were ultimately selected for score system, including age (≥75 years old was ?1, <75 years old was 0), BMI (<24 kg/m2 was 0, 24?28 kg/m2 was ?1,>28 kg/m2 was?2), hypertension grade (grade 1 was 1, grade 2 was 2, and grade 3 was 3), diabetes status (no was 0, yes was?1), antihypertensive drug use (no was 0, yes was?2), alcohol consumption (<60 g/d was 1, ≥60 g/d was 2), uric acid (less than normal was 0, normal was?1, high than normal was?2), LDL cholesterol (<2 mmol/L was 0, 2?4 mmol/L was?1, and>4 mmol/L was?2), and HDL cholesterol (<1.55 mmol/L was 0,≥1.55 mmol/L was 2). Patients with a score more than 0 were classified as the CH group, Conversely, they were assigned to the CI group;its sensitivity, specificity, and accuracy were 74.5％, 77.9％, and 76.4％, respectively. Conclusion: The CI-CH risk scale can help the clinician predict the subtypes of cerebrovascular diseases.

Autophagy, an evolutionarily conserved process by which components of the cell are degraded in lysosomes, may facilitate survival of cancer cells under stress conditions. 8-Azaguanine (8-AG), an inhibitor of purine nucleotide biosynthesis, shows antineoplastic activity in multiple tumor cells. However, chemoresistance has restricted its development as an anticancer agent, and the mechanism of 8-AG resistance is not fully understood. We report here that 8-AG induces a protective autophagy to eliminate its cytotoxicity, and inhibition of autophagy increases cellular sensitivity of cancer cells to 8-AG treatment. Using HepG2 or SMMC-7721 hepatic cancer cell lines, we found that 8-AG inhibited cell viability and induced intrinsic apoptosis, accompanied by the up-regulation of the pro-apoptotic protein BimS, one of Bim (also known as BCL-2-like protein 11, BCL2L11) isoforms. Furthermore, 8-AG treatment enhanced the autophagy flux by promoting the dephosphorylation and activation of Unc-51-like autophagy activating kinase 1 (ULK1) via Akt/mTORC1 (mammalian target of rapamycin complex 1) signaling inhibition. Depletion of autophagy-related gene 7 (ATG7) markedly enhanced the level of BimS, and promoted cell death in response to 8-AG. 8-AG in combination with autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf A1) promoted the 8-AG-induced apoptosis in hepatic cancer cells. Altogether, these findings suggest that autophagy promotes chemoresistance of cancer cells for 8-AG, and blocking autophagy increases cellular sensitivity of cancer cells to 8-AG treatment.