Objective To observe the efficacy and safety of flumatinib conversion in chronic myelogenous leukemia-chronicphase(CML-CP)patients with suboptimal TKI response or intolerance.Methods Patients who did not have the best response or intolerance to first-line imatinib,dasatinib,and nilotinib and switched to flumatinib(600 mg/d)from February 2020 to August 2022 were collected from 5 hospitals from Chongqing and affiliated hospitals of North Sichuan Medical College.The efficacy and safety of flumatinib were observed.The optimal response rate,major molecular response(MMR),cumulative complete cytogenetic response(CCyR)rate,cumulative MMR rate,cumulative deep molecular response(DMR),progression-free survival(PFS),event-free survival(EFS)and adverse reactions in 3,6 and 12 months after treatment were observed and analyzed.Results A total of 100 patients with CML-CP were enrolled,with a median follow-up of 18(3～36)months.The optimal response rate was 92.6％(88/95),94.4％(85/90)and 92.9％(79/85)respectively,at 3,6 and 12 months after treatment.Till August 20,2023,the cumulative CCyR and MMR rate was 98.0％(98/100)and 81.9％(77/94),respectively,the median time to reach CCyR and MMR was 3 months,and cumulative DMR rate was 51.0％(51/100).PFS rate was 100.0％(100/100)and 1-year EFS rate was 85.6％(75/90).The most common non-hematologic adverse reactions of flumatinib were diarrhea and abdominal pain(7.0％),followed by renal dysfunction(6.0％)and musculoskeletal pain(2.0％).The main hematologic adverse reactions were thrombocytopenia(12.0％),anemia(6.0％)and leukopenia(2.0％).Conclusion Flumatinib has better MMR and DMR and is well tolerated in CML-CP patients with TKI resistance or intolerance.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

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.

Objective:To investigate the effects of continuous blood purification (CBP) on mitochondrial function of peripheral blood mononuclear cells and clinical prognosis of patients with traumatic sepsis.Methods:A prospective cohort study was used to analyze the clinical data of 90 patients with traumatic sepsis admitted to the Intensive Care Unit of Shaoxing People′s Hospital from January 2023 to June 2024. Based on standard operating procedures (SOP), patients were divided into CBP group and non-CBP group according to whether they received CBP treatment. The mitochondrial DNA (mtDNA) copy number, activity of mitochondrial respiratory chain complex V, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 in the mononuclear cells on ICU admission and at 12, 24 and 48 hours after treatment were compared between the two groups. Acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU admission and at 48 hours after treatment were detected in the two groups. The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were compared between the two groups.Results:A total of 90 patients with traumatic sepsis were included, comprising 56 males and 34 females, aged 18-82 years [51.3(38.7, 70.6)years], with injury severity score (ISS) of 16-54 points [36.2(17.0, 53.6)points]. There were 52 patients in the CBP group and 38 in the non-CBP group. All the patients were followed up for 7-14 days [10.0(8.0, 12.0)days]. On ICU admission, the mtDNA copy number was 638.5±124.0 in the CBP group and 634.7±122.1 in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the mtDNA copy number in the CBP group was 564.2±105.6, 415.7±83.5 and 303.7±77.0 respectively, significantly lower than 622.9±120.2, 581.5±113.6, 530.7±97.8 in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the mtDNA copy number in both groups continued to decrease compared with that on ICU admission ( P<0.05). On ICU admission, the activity of mitochondrial respiratory chain complex Ⅴ was (74.0±26.0)pg/ml in the CBP group and (72.8±25.3)pg/ml in the non-CBP group ( P>0.05); at 12, 24 and 48 hours after treatment, it was (69.4±24.2)pg/ml, (78.3±26.8)pg/ml and (91.5±33.5)pg/ml respectively in the CBP group, significantly higher than (65.3±23.6)pg/ml, (60.7±19.4)pg/ml and (53.8±16.9)pg/ml in the non-CBP group ( P<0.05 or 0.01); at 12 hours after treatment, it was decreased in both groups compared with that on ICU admission ( P<0.05); at 24 and 48 hours after treatment, it was gradually increased in the CBP group compared with those on ICU admission and at 12 hours after treatment ( P<0.05), while in the non-CBP group, it continued to decrease ( P<0.05). The levels of TNF-α, IL-6 and IL-10 on ICU admission were (51.6±17.1)pg/ml, (174.1±57.3)pg/ml and (67.6±16.2)pg/ml respectively in the CBP group and (49.5±16.7)pg/ml, (177.8±58.7)pg/ml and (65.7±16.6)pg/ml respectively in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the levels of TNF-α in the CBP group were (43.6±15.6)pg/ml, (29.4±12.5)pg/ml and (26.2±10.6)pg/ml respectively, the IL-6 levels were (122.4±41.7)pg/ml, (90.6±33.1)pg/ml, (75.6±24.7)pg/ml respectively and the IL-10 levels were (72.6±18.1)pg/ml, (80.7±20.6)pg/ml, (86.2±22.9)pg/ml respectively, which were significantly lower than (48.8±16.2)pg/ml, (46.5±15.5)pg/ml, (40.0±14.2)pg/ml at 12 hours after treatment, (168.4±51.6)pg/ml, (131.5±42.7)pg/ml, (112.7±35.8)pg/ml at 24 hours after treatment, and (78.6±19.3)pg/ml, (91.1±23.8)pg/ml, (99.4±26.6)pg/ml at 48 hours after treatment in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the levels of TNF-α and IL-6 in both groups continued to decrease, while the levels of IL-10 continued to increase compared with those on ICU admission ( P<0.05). On ICU admission, the APACHE Ⅱ and SOFA scores were (20.6±10.5)points and (6.2±1.9)points in the CBP group and (21.2±11.2)points and (6.7±2.1)points in the non-CBP group ( P>0.05). At 48 hours after treatment, the APACHE Ⅱ and SOFA scores were (13.5±6.6)points and (2.7±0.6)points in the CBP group, which were significantly lower than (18.3±9.3)points and (5.3±1.5)points in the non-CBP group ( P<0.01). At 48 hours after treatment, the APACHE II and SOFA scores in both groups were significantly decreased compared with those on ICU admission ( P<0.05 or 0.01). The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were (13.0±5.7)days, (20.4±8.6)days and 19.2% (10/52) respectively, which were significantly shorter and smaller than (17.6±6.6)days, (26.5±9.4)days and 31.6% (12/38) in the non-CBP group ( P<0.05 or 0.01). Conclusions:CBP treatment may reduce the release of mtDNA by alleviating the mitochondrial damage of the mononuclear cells in patients with traumatic sepsis so that the release of inflammatory factors and cellular apoptosis is reduced, and improve the state of cell energy metabolism and cellular immune function by increasing the activity of mitochondrial respiratory chain complex V in the mononuclear cells, and participate in the reconstruction of immune homeostasis of the body so the inflammatory state and clinical prognosis of the patients are improved.

Kidney Transplantation/adverse effects* ; Magnetics ; Anastomosis, Surgical ; Magnetic Phenomena

Objective:To analyze the characteristics of pancreatic metastatic tumors and evaluate the clinical value of endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA/B) in their diagnosis.Methods:A retrospective analysis was conducted on clinical, radiological, and pathological data of 11 cases with pancreatic metastatic tumors diagnosed by EUS-FNA/B at the First Affiliated Hospital of Naval Medical University between January 2011 and December 2020. Tumor size, number of lesions, time interval between diagnosis of metastatic lesions and primary tumors, radiological and EUS findings and pathological types were recorded, and success rate and diagnostic rate of EUS-FNA/B were analyzed.Results:The 11 patients with pancreatic metastatic tumors had an age range of 43 to 76 years, including 7 males and 4 females. Eight cases presented with symptoms of abdominal pain and poor appetite, 1 case had cervical lymph node enlargement, and 2 cases were detected during routine physical examination. Five cases had abnormal serum tumor markers. All patients had a confirmed history of primary tumors, and the median time interval between diagnosis of pancreatic metastatic lesions and primary tumors was 24 months (-1-124 months). Seven cases had solitary lesions, and 4 cases had multiple nodules under EUS. Eight cases were initially diagnosed clinically as pancreatic lesions or tumor, while 3 cases were considered as pancreatic metastatic tumor. All of 11 cases underwent EUS-FNA/B and were histologically confirmed as pancreatic metastatic tumors. The most common pathological type was lung small cell neuroendocrine cancer ( n=4), followed by renal cell carcinoma ( n=3), and esophageal squamous cell carcinoma ( n=1), pulmonary squamous cell carcinoma( n=1), malignant melanoma ( n=1), and gastric adenocarcinoma ( n=1). Conclusions:The pancreas is not a common target site for tumor metastasis.EUS-FNA/B is a relatively safe minimally invasive method for the diagnosis of pancreatic metastatic tumors.

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q₁, Q₃) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q₁, Q₃) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q₁, Q₃) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ²=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.
Male ; Humans ; Female ; SARS-CoV-2 ; COVID-19/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Objective: To investigate the association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B₁₂ and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B₁₂, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B₁₂ level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B₁₂ level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B₁₂ level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q₁, Q₃) level of plasma vitamin B₁₂ was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B₁₂ level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B₁₂ (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B₁₂ with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.
Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Vitamin B 12 ; Uric Acid ; Cohort Studies ; Hyperuricemia ; Vitamins ; Folic Acid

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.