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.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

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 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 present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Objective:To evaluate the clinical application value of the adaptive aperture by comparing intensity-modulated proton radiotherapy(IMPT) plans using and not using the aperture for brain tumors.Methods:A total of twenty patients treated with postoperative radiotherapy for brain tumors were enrolled in this study. IMPT plans were developed for each patient using and not using the adaptive aperture under the same optimization conditions. The target conformal index (CI) value, target homogeneity index (HI) value, and the dose to normal tissues of the two sets of plans were compared.Results:The IMPT plans designed using the adaptive aperture significantly increased the mean CI value from 0.58 to 0.66, while decreasing the mean 50% prescription dose volume from 797.70 cm 3 to 638.15 cm 3. These plans also reduced the irradiation doses to the cochlea, brainstem, optic chiasm, optic nerve, and lens ( t = 2.06, 3.02, 2.11, 2.58, 2.67, P < 0.05). Additionally, there was no significant difference in the HI value of the target volumes and the machine jumps (MU) between the two sets of plans ( P > 0.05). Conclusions:The adaptive aperture can significantly reduce the irradiation dose to normal tissues outside the target volumes, positively impacting the protection of organs at risk (OARs) around the target values. This demonstrates its great potential for clinical application.

Objective:To discuss the acceptance test of beam performance and mechanical precision of the first Mevion type S250i proton therapy system in China,and verify the stability and reliability of that in clinical treatment.Methods:According to the requirements of acceptance report of manufacturer,the output and range of machine unit(MU),the accuracy and stability of size and position of beam spot,the penumbra and position accuracy of adaptive aperture(AA)of Mevion type S250i proton therapy system,as well as the tests of mechanical properties and functions of the requirement of clinical use,were checked and tested for acceptance.Results:The maximum deviation of MU output was 1.3%,and the maximum deviation of the range was 0.037 g/cm2,and the maximum distal fall-off was 0.465 cm,and the minimum range of energy modulation was 0.21 g/cm2.The maximum deviations of the size of beam spot and the maximum deviation of the position were respectively 0.07 cm and 0.05 cm.The maximum AA penumbra was 0.007 cm,and the AA position accuracy was less than 0.1 cm.Conclusion:The acceptance test of the Mevion type S250i proton therapy system indicates that the parameters of the beam performance and mechanical precision can meet the requirements of the acceptance contract and AAPM-TG224 report of manufacturer,which has verified the machine has better favorable stability and reliability.

Objective:To measure and assess relevant radiation doses at the radiotherapy site of the first domestic single-vault proton therapy system.Methods:The radiation levels of the therapy system during and after beam irradiation were measured, and annual effective doses were assessed for personnel at the site.Results:During beam irradiation, the highest radiation dose was detected at the shielded door of the equipment floor, with a gamma radiation level of 2.140 μSv/h and a neutron radiation level of 0.850 μSv/h. Neutron radiation disappeared immediately once the beams stopped. In contrast, the radiation activated originated mostly from gamma rays. A longer time after beams stopped was associated with lower induced radiation intensity at the same location. Furthermore, a farther distance from the irradiated object corresponded to lower induced radiation intensity at the same time. The assessment result reveal that the annual effective doses to the personnel were at the safe level, with physicists exposed to the highest dose of 2.138 mSv.Conclusions:The radiation level at the studied proton therapy site meets the safety requirement, and the treatment can be performed safely at this site.

Objective:To verify and calibrate the CT modeling curves of three CT devices in RayStation proton treatment planning system (TPS).Methods:CT-mass density (CT-MD) curves were established by CT Hounsfield units of different tissue substitute materials obtained by scanning the model with CT equipment. CT-stopping power (CT-SP) curves were established by calculation based on the chemical composition of various human tissues. The equivalent water thickness of tissue substitute modules was calculated with different CT modeling curves in TPS. The actual equivalent water thickness of various modules was measured by a Bragg peak detector, and compared with the calculated values of TPS to verify the accuracy of different CT models.Results:The differences of CT modeling curves were significantly different under different tube voltage scanning protocols. Compared with CT-MD curves, CT-SP curves based on the stoichiometric calibration were more suitable for proton dose calculation. However, the values of stopping power corresponding to high CT values still needed to be optimized, and the calculation error after calibration was less than 3%.Conclusion:The method of verifying and calibrating CT unit curves of proton TPS is described, proving that the CT-SP curves after stoichiometric calculation are more suitable for proton dose calculation.