OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Objective:To investigate the changes and characteristics of human brucellosis epidemic in Ningxia Hui Autonomous Region (Ningxia), and provide reference for development of brucellosis prevention and control measures in the future.Methods:The data of reported cases of brucellosis in Ningxia in 2022 and 2023 were collected from the "Infectious Disease Reporting Information Management System of China Disease Prevention and Control Information System". Descriptive epidemiological methods were used to compare and analyze the epidemic data.Results:A total of 10 891 cases of human brucellosis were reported in Ningxia in 2022 and 2023, with an average annual incidence rate of 74.94/100 000, and no death cases. The incidence rate of brucellosis decreased from 86.76/100 000 in 2022 to 63.17/100 000 in 2023, with a statistically significant difference (χ 2 = 269.96, P < 0.001). In 2022 and 2023, 22 counties (cities, districts) in Ningxia had reported brucellosis cases, and the incidence rate of brucellosis in each county (city, district) had decreased by 7.88% to 58.43%. There were reports of brucellosis cases in every month of the year. The incidence rates of brucellosis in males were higher than those in females (χ 2 = 831.79, 715.24, P < 0.001). There were statistically significant differences in incidence rates among different age groups (χ 2 = 2 113.28, 1 455.83, P < 0.001), the age distribution were mainly concentrated in the 45 - 59 year old age group [41.62% (2 618/6 290), 41.84% (1 925/4 601)]. The occupational distribution were mainly dominated by farmers and herdsmen [88.71% (5 580/6 290), 89.52% (4 119/4 601)]. Compared with those in 2022, the incidence rates of brucellosis in males and females and all age groups in 2023 were significantly lower (χ 2 = 163.23, 108.56, 14.83, 27.10, 106.81, 110.89, 37.22, P < 0.001). The outbreak of brucellosis had decreased from 6 cases in 2022 to 1 case in 2023. Conclusions:In 2023, the incidence rate of human brucellosis in Ningxia is significantly decreased compared to 2022, the epidemic still affects various regions, with cases occurring in every month of the year. The affected population is mainly male, middle-aged, and farmers and herdsmen.

Objective:To investigate the changes and characteristics of human brucellosis epidemic in Ningxia Hui Autonomous Region (Ningxia), and provide reference for development of brucellosis prevention and control measures in the future.Methods:The data of reported cases of brucellosis in Ningxia in 2022 and 2023 were collected from the "Infectious Disease Reporting Information Management System of China Disease Prevention and Control Information System". Descriptive epidemiological methods were used to compare and analyze the epidemic data.Results:A total of 10 891 cases of human brucellosis were reported in Ningxia in 2022 and 2023, with an average annual incidence rate of 74.94/100 000, and no death cases. The incidence rate of brucellosis decreased from 86.76/100 000 in 2022 to 63.17/100 000 in 2023, with a statistically significant difference (χ 2 = 269.96, P < 0.001). In 2022 and 2023, 22 counties (cities, districts) in Ningxia had reported brucellosis cases, and the incidence rate of brucellosis in each county (city, district) had decreased by 7.88% to 58.43%. There were reports of brucellosis cases in every month of the year. The incidence rates of brucellosis in males were higher than those in females (χ 2 = 831.79, 715.24, P < 0.001). There were statistically significant differences in incidence rates among different age groups (χ 2 = 2 113.28, 1 455.83, P < 0.001), the age distribution were mainly concentrated in the 45 - 59 year old age group [41.62% (2 618/6 290), 41.84% (1 925/4 601)]. The occupational distribution were mainly dominated by farmers and herdsmen [88.71% (5 580/6 290), 89.52% (4 119/4 601)]. Compared with those in 2022, the incidence rates of brucellosis in males and females and all age groups in 2023 were significantly lower (χ 2 = 163.23, 108.56, 14.83, 27.10, 106.81, 110.89, 37.22, P < 0.001). The outbreak of brucellosis had decreased from 6 cases in 2022 to 1 case in 2023. Conclusions:In 2023, the incidence rate of human brucellosis in Ningxia is significantly decreased compared to 2022, the epidemic still affects various regions, with cases occurring in every month of the year. The affected population is mainly male, middle-aged, and farmers and herdsmen.

Objective:To learn about the awareness of brucellosis prevention and control knowledge among people in key areas of Ningxia Hui Autonomous Region (Ningxia), and analyze influencing factors.Methods:From February to March 2023, a multi-stage stratified sampling method was adopted to select residents (aged ≥12 years and resident for ≥6 months) from Yanchi County, Litong District, Pingluo County and Yuanzhou District of Ningxia as the survey subjects. Demographic information such as gender, age, education level, marital status, occupation, region, urban-rural status, as well as knowledge of brucellosis prevention and control were obtained through face-to-face questionnaire surveys. The awareness rate of brucellosis prevention and control knowledge among various populations was calculated and the influencing factors were analyzed by binary logistic regression.Results:A total of 1 592 questionnaires were distributed, of which 1 581 were valid, with an effective rate of 99.31%. There were 704 males, accounting for 44.53% (704/1 581); and 877 females, accounting for 55.47% (877/1 581). The age was (54.09 ± 14.81) years old, ranging from 14 to 88 years old. The education level was mainly primary school or below, accounting for 48.07% (760/1 581). The marital status was mainly married or cohabitating, accounting for 91.84% (1 452/1 581). The occupation was mainly farmers and herdsmen, accounting for 61.92% (979/1 581). In Pingluo County, Litong District, Yuanzhou District and Yanchi County, 392, 403, 396 and 390 people were investigated, respectively. In urban and rural areas, 797 and 784 people were investigated, respectively. The overall awareness rate of brucellosis prevention and control knowledge among the population was 47.82% (756/1 581). Univariate analysis showed that there were statistically significant differences in the awareness rates of brucellosis prevention and control knowledge among different age groups, education levels, marital status, occupation, regions and urban and rural populations ( P < 0.05). Binary logistic regression analysis showed that age, education level, marital status, occupation, urban-rural status were the factors influencing the awareness rate of brucellosis prevention and control knowledge among the population ( P < 0.05). Conclusion:The awareness rate of brucellosis prevention and control knowledge in key areas of Ningxia is relatively low, and age, education level, marital status, occupation, and urban-rural status are the main influencing factors.

Objective:To study the epidemiological characteristics of brucellosis in occupational populations in Ningxia Hui Autonomous Region (referred to as Ningxia), and to provide a reference basis for prevention and control of the disease.Methods:From June to September 2022, blood samples were collected from high-risk occupational groups engaged in cattle and sheep breeding, and slaughtering, etc., in 22 counties (cities and districts) of Ningxia. The Rose Bengal plate agglutination test (RBPT) was used for initial screening, and those who tested positive in the initial screening or suspected cases were further tested by the tube agglutination test (SAT). The serum positive rate was calculated and the number of people infected with Brucella in Ningxia occupational populations was estimated. The epidemic characteristics (regional and population distribution) and clinical manifestations were analyzed. In addition, blood culture method was used to conduct pathogen identification on patients with acute brucellosis and the handling of the outbreaks was analyzed. Results:A total of 163 628 individuals underwent blood test, with 6 613 initially screened positive for RBPT and 6 006 positive for SAT. The serum positive rate was 3.67% (6 006/163 628), 95% CI was 3.58% - 3.76%. It is estimated that there were 18 391 individuals infected with Brucella in the occupational population of Ningxia. The five districts with high serum positive rates were Yanchi County (7.35%, 489/6 649), Hongsibao District (6.72% 469/6 978), Helan County (4.94%, 166/3 363), Litong District (4.77%, 284/ 5 953), and Yuanzhou District (4.47%, 490/10 974). The serum positive rate of male (4.17%, 3 774/90 406) was higher than that of females (3.05%, 2 232/73 222, χ 2 = 135.01, P < 0.001). The serum positive rate increased with age (χ 2trend = 462.93, P < 0.001), with the 60 - < 70 age group having the highest serum positive rate (5.07%, 1 201/23 679). There was a statistically significant difference in serum positive rates among different occupational groups (χ 2 = 158.88, P < 0.001), with the highest serum positive rate in farmers and herdsmen (3.89%, 5 416/139 347). Among 4 892 confirmed patients, fever (3 751, 76.68%), hyperhidrosis (3 306, 67.58%), and lumbar spine injury (2 651, 54.19%) were the most common symptoms. A total of 231 strains of Brucella were isolated, with a detection rate of 36.44% (231/634). Among them, Brucella melitensis Ⅲ accounted for 91.34% (211/231). There had been a total of 5 outbreaks of human brucellosis, with three modes of infection including breeding, slaughtering, and stripping of stillborn sheep, all of which had been effectively managed. Conclusions:The serum positive rate of Brucella in the occupational population of Ningxia is relatively high, with obvious regional and population epidemic characteristics. Patients with clinical symptoms (fever, hyperhidrosis and lumbar spine injury) are more common, and the dominant strain is Brucella melitensis Ⅲ. It is suggested that in the future, monitoring and behavioral intervention should be strengthened in key areas and populations, with a focus on increasing immunization efforts for sheep, while actively carrying out patient treatment.

Objective:To study the epidemiological characteristics of brucellosis in occupational populations in Ningxia Hui Autonomous Region (referred to as Ningxia), and to provide a reference basis for prevention and control of the disease.Methods:From June to September 2022, blood samples were collected from high-risk occupational groups engaged in cattle and sheep breeding, and slaughtering, etc., in 22 counties (cities and districts) of Ningxia. The Rose Bengal plate agglutination test (RBPT) was used for initial screening, and those who tested positive in the initial screening or suspected cases were further tested by the tube agglutination test (SAT). The serum positive rate was calculated and the number of people infected with Brucella in Ningxia occupational populations was estimated. The epidemic characteristics (regional and population distribution) and clinical manifestations were analyzed. In addition, blood culture method was used to conduct pathogen identification on patients with acute brucellosis and the handling of the outbreaks was analyzed. Results:A total of 163 628 individuals underwent blood test, with 6 613 initially screened positive for RBPT and 6 006 positive for SAT. The serum positive rate was 3.67% (6 006/163 628), 95% CI was 3.58% - 3.76%. It is estimated that there were 18 391 individuals infected with Brucella in the occupational population of Ningxia. The five districts with high serum positive rates were Yanchi County (7.35%, 489/6 649), Hongsibao District (6.72% 469/6 978), Helan County (4.94%, 166/3 363), Litong District (4.77%, 284/ 5 953), and Yuanzhou District (4.47%, 490/10 974). The serum positive rate of male (4.17%, 3 774/90 406) was higher than that of females (3.05%, 2 232/73 222, χ 2 = 135.01, P < 0.001). The serum positive rate increased with age (χ 2trend = 462.93, P < 0.001), with the 60 - < 70 age group having the highest serum positive rate (5.07%, 1 201/23 679). There was a statistically significant difference in serum positive rates among different occupational groups (χ 2 = 158.88, P < 0.001), with the highest serum positive rate in farmers and herdsmen (3.89%, 5 416/139 347). Among 4 892 confirmed patients, fever (3 751, 76.68%), hyperhidrosis (3 306, 67.58%), and lumbar spine injury (2 651, 54.19%) were the most common symptoms. A total of 231 strains of Brucella were isolated, with a detection rate of 36.44% (231/634). Among them, Brucella melitensis Ⅲ accounted for 91.34% (211/231). There had been a total of 5 outbreaks of human brucellosis, with three modes of infection including breeding, slaughtering, and stripping of stillborn sheep, all of which had been effectively managed. Conclusions:The serum positive rate of Brucella in the occupational population of Ningxia is relatively high, with obvious regional and population epidemic characteristics. Patients with clinical symptoms (fever, hyperhidrosis and lumbar spine injury) are more common, and the dominant strain is Brucella melitensis Ⅲ. It is suggested that in the future, monitoring and behavioral intervention should be strengthened in key areas and populations, with a focus on increasing immunization efforts for sheep, while actively carrying out patient treatment.

Objective:To compare the efficacies of robot-assisted unilateral and manual unilateral/bilateral puncture kyphoplasty (PKP) for the treatment of osteoporotic thoracolumbar fracture (OTLF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 OTLF patients admitted to First Affiliated Hospital of Kunming Medical University from April 2021 to May 2022. The patients included 28 males and 36 females, aged 57-88 years [(74.5±5.6)years]. Fracture segments were 12 patients from T 1-T 9, 32 from T 10-L 2, and 20 from L 3-L 5. All the patients were treated with PKP. Among them, 25 patients underwent manual unilateral puncture (manual unilateral group), 18 patients underwent manual bilateral puncture (manual bilateral group), and 21 patients underwent robot-assisted unilateral puncture (robot-assisted unilateral group). The operation time, channel establishment time, intraoperative blood loss, intraoperative fluoroscopy times, bone cement injection volume, and bone cement spatial distribution score were compared among the three groups. The visual analogue score (VAS), Oswestry disability index (ODI) and Cobb angle of kyphosis were compared among the three groups before operation, at 3 days and 3 months after operation, and at the last follow-up. The incidence of complications was compared. Results:All the patients were followed up for 6-10 months [(7.0±0.9)months]. The operation time of the manual unilateral group was (30.2±6.1)minutes, which was shorter than (37.9±8.9)minutes of the robot-assisted unilateral group and (49.0±10.2)minutes of the manual bilateral group; the operation time of the robot-assisted unilateral group was markedly shorter than that of the manual bilateral group (all P<0.05). The channel establishment time of the robot-assisted unilateral group was (4.7±1.4)minutes, which was markedly shorter than (10.4±4.4)minutes of the manual unilateral group and (21.7±6.2)minutes of the manual bilateral group (all P<0.05). The intraoperative blood loss of the robot-assisted unilateral group was (23.8±7.2)ml, which was less than (34.3±7.7)ml of the manual unilateral group and (55.9±18.7)ml of the manual bilateral group (all P<0.05). The number of intraoperative fluoroscopy of the robot-assisted unilateral group was (12.1±2.5)times, which was markedly less than (21.2±5.9)times of the manual unilateral group and (39.6±9.5)times of the manual bilateral group (all P<0.05). The channel establishment time, intraoperative blood loss and intraoperative fluoroscopy times of the manual unilateral group were markedly shorter or less than those of the manual bilateral group (all P<0.05). The bone cement injection volume and bone cement distribution score of the robot-assisted unilateral group were (4.7±1.3)ml and (7.9±1.2)points, which were not statistically different from (5.7±1.3)ml and (8.7±1.1)points of the manual bilateral group (all P>0.05), but were markedly higher than (3.0±1.3)ml and (5.1±1.8)points of the manual unilateral group (all P<0.05). There were no significant differences in VAS, ODI and Cobb angle among the three groups at 3 days, 3 months after operation and at the last follow-up (all P>0.05), but which were all lower than those before surgery (all P<0.05). There were no significant differences in VAS, ODI and Cobb angle among three groups before operation, at 3 days, 3 months after surgery and at the last follow-up (all P>0.05). The complication rate was 4.8% (1/21) of the robot-assisted unilateral group, 32.0% (8/25) of the manual unilateral group, and 33.3% (6/18) of the manual bilateral group, with no significant difference between the manual unilateral group and the manual bilateral group ( P>0.05), but both of which was markedly higher than that of the robot-assisted unilateral group ( P<0.05). Conclusion:Robot-assisted unilateral puncture and manual unilateral/bilateral puncture PKP can both achieve satisfactory results for the treatment of OTLF, but robot-assisted unilateral puncture has shorter channel establishment time, less intraoperative blood loss and intraoperative fluoroscopy times, and lower complication rate.

Objective:To learn about the epidemiological characteristics and trends of brucellosis in Ningxia Hui Autonomous Region (Ningxia), and to provide reference for formulation of brucellosis prevention strategies and identification of key areas.Methods:The case data from 2004 to 2019 were collected from the "China Disease Prevention and Control Information System Infectious Disease Monitoring and Reporting System", and descriptive epidemiological methods were used to analyze the distribution of cases (time, population, and regional distribution).Results:From 2004 to 2019, a total of 15 337 human brucellosis cases and 1 death case were reported in Ningxia. The average annual incidence rate was 15.21/100 000, ranging from 0.02/100 000 to 44.83/100 000. The difference in incidence rate in different years was statistically significant (χ 2 = 14 731.60, P < 0.001). Among them, from 2004 to 2010, the incidence rate was low, with an average annual incidence rate of 1.32/100 000; from 2011 to 2019, it entered a high incidence stage, with an average annual incidence rate of 24.83/100 000. Brucellosis occured in every month of the year, and the onset time was mainly in March to September, accounting for 71.60% (10 981/15 337); seasonal indexes from April to August was all > 100%, with obvious seasonality. The age of onset mainly concentrated in 20 - < 70 years old, accounting for 89.60% (13 742/15 337); males were significantly more than females, with a sex ratio of 2.66 ∶ 1.00 (11 141/4 196); the occupations were mainly farmers and herdsmen, accounting for 86.03% (13 194/15 337). Since 2014, cases had been reported in 22 counties (districts, cities) in the region, all of which were all severely endemic areas; the top three counties (districts) with incidence rate were Yanchi County (103.73/100 000), Hongsibao District (56.01/100 000) and Tongxin County (29.18/ 100 000), respectively, the difference between different regions was statistically significant (χ 2 = 3.80, P < 0.001). Conclusions:The incidence rate of brucellosis in Ningxia is on the rise, and the epidemic situation is severe. It is recommended to carry out active and effective intervention measures in areas with high incidence of brucellosis to curb the further spread of brucellosis.

Objective To analyze the epidemic situation of inter-human brucellosis in Zhongwei City of Ningxia from 2005 to 2017,and to provide basis for making scientific and effective prevention and control measures of the disease.Methods Incidence data of brucellosis were collected in Zhongwei City from 2005 to 2017 and prevalence trends and distribution characteristics (place,time,and population distribution) were analyzed by descriptive epidemiological method.Results A total of 1 880 human brucellosis cases were reported in Zhongwei City from 2005 to 2017.The incidence of brucellosis in 2012 and 2015 was 5.03/100 000 and 61.80/100 000,which showed a dramatic and rapid ascent (x2trend =681.40,P ＜ 0.05),while after 2016,it showed a downward trend (xtrend =324.85,P ＜ 0.05),and in 2017 the reported incidence dropped to 25.13/100 000.Zhongning and Haiyuan Counties showed a high incidence from 2005 to 2017,and the incidence was 39.79％(748/1 880) and 36.06％ (678/1 880),respectively;April to September was the peak season;the sex ratio was 2.72:1.00 (1 375/505);1 379 cases (73.35％)occurred between 30 and 64 years old,and 1 616 cases (85.96％) occurred among farmer.Conclusion After 2016,the incidence of human outbreaks in Zhongwei City has declined;Zhongning and Haiyuan Counties are the key areas of morbidity;the key population for prevention and control is farmer.

Objective To study the effect of lipopolysaccharide ( LPS ) on the activity of primary cultured macrophages and the distribution of divalent metal transporter 1 ( DMT1 ) and ferroportin 1 ( FPN1 ) .Methods Primary cell culture , MTT chromotest , cytochemistry chromotest and cell immunofluorescence techniques were used in this work . Results DMT1 was mainly distributed in the cytoplasm , which illuminates that DMT1 mediates the macrophage intracellular transit of iron from phagolysosome to cytoplasm .FPN1 was distributed in the cytoplasm and membrane , and the cytoplasm was the main site of FPN 1 distribution in macrophages .Conclusion Iron liberation from heme inside the phagolysosome occurs after erythrophagocytosis and it is possible that FPN 1 mediates intracellular transit of iron released by heme catabolism .The study found that LPS promoted the cell growth and this effect was reached to the peak in the 10 -5μg/L LPS group, but the cell growth was blocked with the increase of LPS concentration .