The inherent clinical uncertainties, substantial costs, and small patient cohorts of orphan drugs limit the applicability of randomized controlled trial (RCT)-based health technology assessments (HTAs) in guiding coverage criteria, sustainable financing models, and equitable reimbursement frameworks for medical financial assistance policies for rare diseases.The digital transformation in healthcare system leads to solutions to the challenges in designing the policy by using data-driven decision-making. This article summarizes the decision-making issues in policy design, discusses the current status and trends of digital transformation, and analyzes the important new opportunities for AI-driven policy design for medical financial assistance policies for rare diseases. Decision-making that is digital intelligence driven and using techniques such as big data analytics and real-world research methods will enhance targeting efficiency, improve the quality of financing, and realize the performance-based reimbursement in the medical financial assistance, providing significant value in facilitating the policy reform and development for rare diseases healthcare.

Objective To investigate the etiology, symptoms, diagnosis, surgical treatment, and outcomes of acute necrotizing mediastinitis (ANM) in order to guide future diagnosis and treatment of ANM. Methods The clinical data of patients with ANM referred to West China Hospital, Sichuan University from March 2012 to April 2021 were retrospectively analyzed. The etiology, clinical manifestations, demographic characteristics, bacterial culture results, surgical approach and prognostic factors of these patients were summarized. Results A total of 176 patients were enrolled in this study. The median age was 60 ( 0-84) years. There were 124 (70.5%) males and 52 (29.5%) females. The most common origin of infection was neck (n=66, 37.5%). The most common symptom was fever (n=85, 48.3%). Streptococcus constellatus represented the most common pathogens in secretion culture. Surgical treatment was administered to 119 (67.6%) patients through different approaches, including 54 (30.7%) patients of cervical approach, 9 (5.1%) patients of thoracotomy, 18 (10.2%) patients of video-assisted thoracoscopic surgery (VATS), 7 (4.0%) patients of cervical combined with thoracotomy, 30 (17.0%) patients of cervical combined with VATS, and 1 (0.6%) patient of subxiphoid approach. Among this cohort, 144 (81.8%) patients were cured, while 32 (18.1%) patients died. Age-adjusted Charlson comorbidity index (OR=2.95, P=0.022), perioperative sepsis (OR=2.84, P=0.024), and non-surgical treatment (OR=2.41, P=0.043) were identified as independent predictors of poor outcomes. Conclusion For patients with corresponding history and manifestations of ANM, it is crucial to go through imaging examination to confirm the presence of an abscess and guide the selection of surgical approach. Once the diagnosis of ANM is made, it is imperative to promptly perform surgical intervention for effective drainage. Our study highlights the significance of age-adjusted Charlson comorbidity index, perioperative sepsis and surgical treatment in predicting patients’ outcomes.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective To investigate the efficacy and the collective brain responses of acupuncture for post-stroke limb numbness.Methods A total of 24 patients with post-stroke limb numbness and 23 matched healthy participants were recruited.Both groups received coordinated acupuncture treatment to regulate their physical and mental state,three times a week for 4 weeks.Changes in limb numbness assessed by the visual analog scale(VAS)were observed before and after acupuncture.Functional magnetic resonance imaging(fMRI)scans were conducted on the participants during the scanning process with acupuncture intervention.Blood oxygen level-dependent(BOLD)data were collected in three states:resting state,acupuncture task state,and needle retention state.Data processing was performed using software such as fMRIPrep and brainIAK.Intersubject correlation(ISC)analysis was conducted to compare the ISC values of different brain regions between the two groups under different conditions.Results Acupuncture treatment significantly reduced the VAS scores of limb numbness.No significant changes in ISC values in both groups during resting state.Under acupuncture conditions,the patient group exhibited significantly increased ISC values in the left precentral gyrus,left paracentral lobule,left postcentral gyrus,left insula,left anterior cingulate gyrus,right middle frontal gyruss and right anterior cingulate gyrus.Under the needle retention condition,a slight negative activation was observed in the bilateral precentral gyrus of the control group.In the patient group,the ISC values of the left superior frontal gyrus,left precentral gyrus,left paracentral lobule,left precuneus,left postcentral gyrus,left insula,left anterior cingulate gyrus,left thalamus,right superior frontal gyrus,right middle frontal gyrus,right precentral gyrus,and right anterior cingulate gyrus showed a significant increase compared to the resting state.Conclusion Acupuncture can improve post-stroke limb numbness symptoms and induce a specific pattern of collective brain activation in patients.This activation involves the precentral gyrus,postcentral gyrus,thalamus,insula,frontal lobe and cingulate gyrus.Acupuncture may enhance the processing of sensory information by activating the somatosensory-motor network and the cortical-thalamic-cortical loop.It may also modulate the central executive network and the descending pain control pathway to promote the relief of pain symptoms.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To analyze the influencing factors related to false-negative results of interferon-γ release assay (IGRA) QFT-GIT in patients with confirmed pulmonary tuberculosis.Methods:Clinical data of 389 patients with bacteriologically confirmed pulmonary tuberculosis who underwent QFT-GIT in Quzhou Hospital Affiliated to Wenzhou Medical University between January 1 and December 31 2020 were retrospectively analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors related to the false-negative results of QFT-GIT.Results:Among 389 confirmed patients, 347 cases had positive QFT-GIT results and 42 cases had negative results. Univariate analysis showed that the false-negative results of QFT-GIT were associated with low BMI, reduced CD4 + T lymphocyte count, decreased lymphocyte count, increased C-reactive protein, negative sputum smear, anemia, diabetes mellitus, malignant tumor and sepsis ( P<0.05 or P<0.01). Multivariate conditional logistic regression analysis showed that BMI <18.5 kg/m 2( OR=1.585, 95% CI 1.076-2.336), complicated with diabetes( OR=5.157, 95% CI 2.340-11.365), malignant tumors ( OR=5.596, 95% CI 2.048-15.295)and sepsis ( OR=4.141, 95% CI 1.042-16.459) were independent risk factors for the false-negative results of QFT-GIT ( P<0.05 or P<0.01). Conclusion:When the pulmonary tuberculosis patients are extreme emaciation, complicated with diabetes, malignant tumor or sepsis, the QFT-GIT results will be false negative.

Objective     To compare the perioperative results between uniportal and three-portal thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Methods     Electronic databases including PubMed, Web of Science, EMbase, CNKI, Wanfang were systematically searched from the establishment of each database until April 2022. Literature screening, data extraction and bias risk assessment were independently conducted by two researchers. All combined results were performed by RevMan 5.3 and Stata 16.0. The quality of the literature and the risk of bias were evaluated using the Cochrane Bias Risk Assessment Tool. Results     Eighteen eligible randomized controlled trials (1 597 patients) were identified eventually, including 800 patients undergoing uniportal thoracoscopic lobectomy and 797 patients undergoing three-portal thoracoscopic lobectomy. Meta-analysis results showed that compared to the three-portal approach, uniportal lobectomy took longer operation time (WMD=7.63, 95%CI 2.36 to 12.91, P=0.005) with less intraoperative blood loss (WMD=–28.81, 95%CI –42.54 to –15.08, P<0.001). Furthermore, patients undergoing uniportal lobectomy achieved lower visual analogue score within 24 hours after the operation (WMD=–1.60, 95%CI –2.26 to –0.94, P<0.001), less volume of drainage after the operation (WMD=–25.30, 95%CI –46.22 to –4.37, P=0.020), as well as shorter drainage duration (WMD=–0.36, 95%CI –0.72 to –0.01, P=0.040). Besides, patients undergoing uniportal lobectomy were also observed with shorter length of hospital stay (WMD=–2.28, 95%CI –2.68 to –1.88, P<0.001) and lower incidence of postoperative complications (RR=0.49, 95%CI 0.38 to 0.63, P<0.001). However, the number of lymph nodes harvested during the operation (WMD=–0.01, 95%CI –0.24 to 0.21, P=0.930) was similar between the two groups. Conclusion     Both uniportal and three-portal thoracoscopic lobectomy for NSCLC are safe and feasible. The uniportal approach is superior in reducing short-term postoperative pain, postoperative complications and shortening the length of hospital stay.

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H 2O 2). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-β-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-β-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

Pre-testing preparation is the basis and starting point of genetic testing.The process includes collection of clinical information,formulation of testing scheme,genetic counseling before testing,and completion of informed consent and testing authorization.To effectively identify genetic diseases in clinics can greatly improve the diagnostic rate of next generation sequencing (NGS),thereby reducing medical cost and improving clinical efficacy.The analysis of NGS results relies,to a large extent,on the understanding of genotype-phenotype correlations,therefore it is particularly important to collect and evaluate clinical phenotypes and describe them in uniform standard terms.Different types of genetic diseases or mutations may require specific testing techniques,which can yield twice the result with half the effort.Pre-testing genetic counseling can help patients and their families to understand the significance of relevant genetic testing,formulate individualized testing strategies,and lay a foundation for follow-up.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.