Objective To analyze the voice acoustic characteristics in Parkinson's disease(PD)patients,and to study the correlation between voice features and the severity of disease.Methods A total of 83 patients with PD were selected from the Dongguan Songshan Lake Central Hospital from January 2021 to January 2022 as the experi-mental group,and 87 healthy subjects were enrolled as the control group.All the PD patients were tested with Uni-fied Parkinson's Disease Rating Scale(UPDRS).The vioce samples of all subjects were collected and acoustic char-acteristic were analyzed using speech processing software.The acoustic parameters of two groups were compared ac-cording to sex,and the correlation between vioce features and the severity of disease was analyzed.Results A total of 3 720 speech samples were collected,including 1 895 for PD and 1 825 for the controls.The maximum fundamen-tal frequency,fundamental frequency range and fundamental frequency period change rate were lower than the con-trol group,and the amplitude disturbance was higher than the control group,the differences were statistically signif-icant(P＜0.05).There was a negative correlation between UPDRS-Ⅲ score and the rate of fundamental frequency period change in female patients with PD(r=-0.617,P＜0.05).Conclusion The changes in acoustic parameters are mainly manifested as the decrease in the maximum fundamental frequency,range of fundamental frequency and the change rate of fundamental frequency period,and the increase in the the amplitude disturbance.The rate of fun-damental frequency period change may be used as an indicator to evaluate the severity in female patients with PD.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Dynamic multi-leaf collimator, which has the function of radiation beam shaping, is a key executive component of tumor precise radiotherapy, and plays a core role in improving the accuracy, efficiency and quality of radiotherapy. A new type of collimator leaf end structure with circular arc and plane combination was studied, and collimator penumbra performance analysis model combining analytical expression and graphic analysis was developed. The influence of leaf end structure on penumbra was analyzed quantitatively, and a set of three-dimensional structure design of dynamic multi-leaf collimator was completed. The feasibility of the structural design and analysis model was verified through experimental measurements.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Particle Accelerators ; Neoplasms ; Radiotherapy Dosage

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective:To analyze the accuracy of diagnostic indicators for perioperative venous thromboembolism（VTE）in orthopedic patients.Methods:A retrospective case-control study was conducted to analyze the clinical data of 109 patients who underwent initial total hip arthroplasty（THA），total knee arthroplasty（TKA）or proximal femoral nail antirotation（PFNA）in Hechuan District People ’s Hospital of Chongqing from January 2015 to September 2019. There were 55 males and 54 females，with age range of 18-76 years［（46.3 ± 11.2）years］. Of all，54 patients underwent unilateral THA due to femoral head necrosis and femoral neck fracture，36 patients underwent unilateral TKA due to osteoarthritis and 19 patients underwent PFNA due to proximal femoral fracture. VTE was confirmed in 47 patients（VTE group），and did not occur in 62 patients（non-VTE group）. Venous blood was collected from all patients on admission and at postoperative 1，3，5，7 days to measure levels of plasma D-dimer，serum interleukin（IL）-18 and vascular endothelial growth factor（VEGF）. The accuracy of the above indicators in VTE diagnosis was analyzed by using receiver operating characteristic（ROC）curve. Results:In both groups，preoperative levels of D-dimer，IL-18 and VEGF were significantly lower than those postoperatively，and each indicator showed significant difference at each time points after operation（ P < 0.05 or 0.01）. Moreover，levels of D-dimer，IL-18 and VEGF in VTE group were significantly higher than those in non-VTE group at each time after operation（ P < 0.05 or 0.01）. Area under the ROC curve（AUC）for D-dimer was 0.839（95% CI 0.729-0.887），with the optimal cut-off of 5.5 μg/ml，sensitivity of 87.0%，specificity of 79.0% and Youden index of 0.67. AUC for IL-18 was 0.817（95% CI 0.719-0.857），with the optimal cut-off of 293.5 pg/ml，sensitivity of 67.0%，specificity of 87.1% and Youden index of 0.457. AUC for VEGF was 0.837（95% CI 0.784-0.918），with the optimal cut-off of 510.8 pg/ml，sensitivity of 81.0%，specificity of 79.0% and Youden index of 0.583. AUC for combined D-dimer，IL-18 and VEGF was 0.870（95% CI 0.747-0.992），with the sensitivity of 87.2%，specificity of 83.4% and Youden index of 0.606. Conclusions:For diagnosis of perioperative VTE in orthopedic patients，serum VEGF is relatively accurate，while serum IL-18 has a low accuracy. However，the diagnostic rate of VTE can be improved by combining indicators of D-dimer，IL-18 and VEGF.

OBJECTIVE：To study the m edical insurance budget impact analysis （BIA）guidelines or nomative documents of some European countries ，and to provide the suggestions for the formulation and implementation of medical insurance BIA guidelines in China. METHODS ：Medical insurance BIA guidelines or related documents in European countries such as Ireland ， France，Poland，Belgium and UK were retrieved to summarize and comparatively analyze the general analysis framework and special specification. The formulation of medical insurance BIA guideline in China and the suggestions were put forward. RESULTS & CONCLUSIONS ：The above-mentioned medical insurance BIA guidelines or documents of the five European countries generally study the impact of the cost of health technology on resources within 3-5 years from the perspective of budget holders. The analysis framework of the guidelines or documents is basically the same ，but the guidelines or documents are adjusted according to the characteristics of national health system in terms of the positioning of medical insurance BIA ，the scope of cost data inclusion ， model design ，population subgroup analysis and so on. For example ，Ireland had special requirements on cost data inclusion ， sensitivity analysis and data source ，while France had detailed regulations on medical insurance BIA model ，sensitivity analysis and presentation of medical insurance BIA results. Our country should pay attention to the role of medical insurance BIA in medical and health decision-making ，formulate China ’s medical insurance BIA guidelines to standardize empirical research ，and combine the characteristics of China ’s health system when formulate the guideline. It is suggested that China ’s medical insurance BIA guidelines should at least include research perspective ，research time limit and discount ，reference situation ，target population ， cost，market share ，data source ，uncertainty analysis and other overall framework or basic elements to ensure the smooth operation of medical and health funds.

Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention.We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.
Bacteria ; genetics ; Bacterial Infections ; epidemiology ; microbiology ; transmission ; Bacterial Typing Techniques ; Disease Outbreaks ; prevention & control ; Genome, Bacterial ; Genotype ; Humans ; Population Surveillance ; Whole Genome Sequencing

Objective:To construct an adeno-associated vector expressing Snail "tough decoy" (TUD).Methods:The nucleotide sequence of Snail gene were obtained from GenBank,then 2 cDNAs were designed and synthesized coding expression of small hairpin RNAs for Snail genes.The pAAV-U6-shRNA-Snail-TUD-EGFP expression vector was constructed by molecular biological techniques.Then pAAV-U6-shRNA-Snail-TUD-EGFP was co-transfected with Helper Free adeno-associated virus system pAAV-RC and pAAV-Helper into AAV-293 cell line to form rAAY-U6-shRNA-Snail-TUD(shRNA-Snail).The silencing effect of shRNA-Snail in Tca8113 and Cal-27 cells was detected by RT-PCR.The titer of the virus was measured.The expression level of green fluorescent protein in AAV-293 cells was monitored by the fluorescent microscopy.Results:The result of gene sequencing showed that shRNA-Snail was successful constructed in pAAV-U6-shRNA-Snail-TUD-EGFP vector.The titer of the recombined virus was 4.4 × 1010/ml.The Snail mRNA and protein expression level was significantly reduced in Tca8113 and Cal-27 cells by rAAY-U6-shRNA-Snail-TUD-EGFP transfection.Conclusion:rAAY-U6-shRNA-Snail-TUD-EGFP may inhibite Snail gene expression in cells.

Objective To investigate the prevalence rate of healthcare-associated infection(HAI)in Xiangya Hospital,and provide reference for preventing and controlling HAI.Methods The cross sectional surveys on preva-lence rates of HAI,cross-sectional antimicrobial use,and bacterial detection among all hospitalized patients on the given days in 2000-2014 (except 2006)were carried out by combination of bedside investigation and medical record reviewing.Results The prevalence rates of HAI in 2000-2014 decreased from 6.30% to 3.91%,difference was statistically significant (χ2 = 35.14,P < 0.001 );prevalence rates of community-associated infection(CAI)were 15.61%-15.76%,there was no significant difference among each year.General intensive care unit (ICU)had the highest prevalence rate;respiratory tract was the most common site of both HAI and CAI;urinary catheterization rate showed a decreased tendency,arteriovenous catheterization rate showed a increased tendency,difference were both significant(χ2 = 5.21,96.24,respectively,both P <0.001).In 2008 - 2014,pathogenic detection rates for specimens from patients receiving therapeutic antimicrobial agents were 36.37%-44.51%,from patients with HAI were 34.00%-44.99%,detection rate of pathogens causing HAI were 41.57%-68.48%,all showed a increased tendency,difference was significant (χ2 = 22.78,10.03,26.49,respectively,all P < 0.001 ).Gram-negative bacteria were the main pathogens causing infection;both cross sectional and combination antimicrobial usage rates declined (P < 0.05 ).Conclusion Prevention and control of HAI,and antimicrobial management has achieved preliminary success,prevalence rate of HAI and cross sectional antimicrobial usage rate declined obviously,the main pathogen is gram-negative bacteria,and the major infection site is lower respiratory tract.