Objective To explore the effects of oral voriconazole(VRC)on the pharmacokinetics of tacrolimus(TAC)in renal transplant patients.Methods Renal transplant patients who had taken TAC orally for more than 2 days and achieved steady-state plasma concentration before taking VRC.The trough concentration of TAC was measured on the 3rd,5th and 10th days after VRC 200 or 400 mg·d-1 administration.The trough concentration(C0)of TAC was determined by high performance liquid chromatography.The genotypes of TAC were determined by polymerase chain reaction and the pharmacokinetics of TAC after combined use of VRC were compared.Results After the use of VRC,the TAC C0 of 11 renal transplant patients was 3-8 μg·L-1,and the concentration of TAC ranged from 50.00％to 87.50％of the original dose.Additionally,the impact of VRC on TAC varied significantly among individuals.The mean TAC C0 value after VRC administration was significantly higher than the value before VRC[(12.14±3.89)vss(5.20±2.79)μg·L-1].Eleven renal transplant patients were grouped according to cytochrome P450(CYP)2C19-CYP3A5 gene polymorphism,under the condition of combined administration,the C0/dose of TAC in the slow metabolizer group was higher than that in the fast metabolizer group on the 3rd,5th and 10th days[(582.10±252.30)vs(439.03±166.08),(873.71±449.22)vs(666.60±168.00),(852.10±505.73)vs(261.50±81.98)μg·L-1·mg-1·kg;all P＜0.01].Conclusion TAC pharmacokinetics was significantly affected by the VRC in renal transplant recipients,and the principle that TAC dose needed to be reduced by one-third of the original dose was no longer applicable,which may be related to the pharmacokinetics of the VRC itself and the gene polymorphism of CYP2C19/CYP3A5 enzyme.It is recommended to regularly monitor the concentration of TAC when VRC and TAC are used in combination.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

Objective To propose a Q factor-based fatigue vibration evaluation method of the ultrasonic knife tip.Methods Firstly,an ultrasonic cutter fatigue testing table was established to realize repeated cutting,which was composed of a power supply module,a three-axis moving module,an ultrasonic cutter clamping module and a control module.Secondly,10 ultrasonic knives of some brand underwent fatigue testing with the table,during which non-contact measurement of the ultrasonic knife tip vibration was carried out and the Q factors were calculated at the five periods of the fatigue test,including the periods before cutting,after 500 times of cutting,after 1 000 times of cutting,after 2 000 times of cutting and after 3 000 times of cutting.Finally,the average cutting speed and burst pressure for coagulated vessels were computed at each period to validata the effectiveness of the method proposed.Results It's indicated that Q factor could effectively reflect the fatigue degradation of the ultrasonic knife tip,while the average cutting speed and burst pressure for coagulated vessels were difficult to efficiently evaluate the fatigue degradation level of the ultrasonic knife tip due to the uncertainty factors in the measurement process.Conclusion The proposed Q factor-based evaluation method can directly evaluate fatigue vibration of the ultrasonic knife tip in an accurate and quantitative manner.[Chinese Medical Equipment Journal,2024,45(6):17-22]

Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]

Objective To explore the incidence of long CO VID symptoms in patients infected with Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods According to the inclusion and exclu-sion criteria of literatures,relevant studies without language restrictions published up to 2024 were retrieved from both Chinese and English databases.The Chinese databases were China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP databases,and the foreign databases were PubMed,Embase,and Web of Science.Three-step screening was used to select literatures,and Stata 17.0 software was used for analysis.Results The incidence of at least one sequelae in patients infected with Omicron variant was 29.62％.The most common symptoms included fatigue(19.10％),joint or muscle pain(11.06％),memory loss(9.71％),brain fog(8.80％),cough(8.42％),headache(7.26％),and sore throat(6.68％).Subgroup analysis results showed that with the extension of follow-up(3 months vs 6 months),the incidence of smell or taste changes was significantly re-duced(7.22％vs 0.78％).The higher the proportion of women(＜50％vs 50％-65％vs＞65％),the higher the incidence of joint or muscle pain(1.09％vs 4.62％vs 19.53％);the greater the median age(≥45 years vs＜45 years),the higher the incidence of chest pain or chest distress(0.90％vs 3.86％),all with statistically significant differences(all P＜0.05).Conclusion Incidence of long COVID in Omicron-infected patients is high and can cause various symptoms.Follow-up time,median age and gender proportion have significant impacts on the incidence of some symptoms.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Objective:To explore the clinical characteristics,molecular characteristics,treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia(Ph-like ALL)with a therapeutic target.Methods:A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021.The data of age,gender,white blood cell(WBC)count at initial diagnosis,genetic characteristics,molecular biological changes,chemotherapy regimen,different targeted drugs were given,and minimal residual disease(MRD)on day 19,MRD on day 46,whether hematopoietic stem cell transplantation(HSCT)were retrospective analyed,and the clinical characteristics and treatment effect were summarized.Survival analysis was performed by Kaplan-Meier method.Results:The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients,10 patients were treated with targeted drugs during treatment,and 3 patients were bridged with HSCT,1 patient died and 2 patients survived.Among the 24 patients who did not receive HSCT,1 patient developed relapse,and achieved complete remission(CR)after treatment with chimeric antigen receptors T cells(CAR-T).The 3-year overall survival,3-year relapse-free survival and 3-year event-free survival rate of 27 patients were(95.5±4.4)％,(95.0±4.9)％and(90.7±6.3)％respectively.Conclusion:Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children,combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor,and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.
Humans ; Thyroidectomy/methods* ; Prospective Studies ; Watchful Waiting/methods* ; Thyroid Neoplasms/pathology* ; Disease Progression ; Thyroid Cancer, Papillary/surgery*