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Diabetic foot ulcer (DFU) is a predominant complication of diabetes mellitus with poor prognosis accompanied by high amputation and mortality rates. Dang-Gui-Si-Ni decoction (DSD), as a classic formula with a long history in China, has been found to improve DFU symptoms. However, mechanism of DSD for DFU therapy remains unclear with no systematic elaboration. In vivo, following establishment of DFU rat model, DSD intervention with low, medium and high doses was done, with Metformin (DM) as a positive control group. With wound healing detection, pathological changes by HE staining, inflammatory factor expression by ELISA and qRT-PCR, oxidative stress levels by ELISA, and AGEs/RAGE/TGF-β/Smad2/3 expression by Western blot were performed. In vitro, intervention with LY2109761 (TGF-β pathway inhibitor) based on DSD treatment in human dermal fibroblast-adult (HDF-a) cells was made. Cell viability by CCK8, migration ability by cell scratch, apoptosis by flow cytometry, and AGEs/RAGE/TGF-β/Smad2/3 expression by Western blot were measured. DFU rats exhibited elevated AGEs/RAGE expression, whereas decreased TGF-β1 and p-Smad3/Smad3 protein expression, accompanied by higher IL-1β, IL-6, TNF-α levels, and oxidative stress. DSD intervention reversed above effects. Glucose induction caused lower cell viability, migration, TGF-β1 and p-Smad3/Smad3 protein expression, with increased apoptosis and AGEs/RAGE expression in HDF-a cells. These effects were reversed after DSD intervention, and further LY2109761 intervention inhibited DSD effects in cells. DSD intervention may facilitate wound healing in DFU by regulating expression of AGEs/RAGE/TGF-β/Smad2/3, providing scientific experimental evidence for DSD clinical application for DFU therapy. [ABSTRACT FROM AUTHOR]

Education policies align with evolving needs and changes in education. Two years ago, the double reduction policy was widely welcomed. But new challenges have emerged now, it is necessary to examine whether it still meets parental expectations, and whether adjustments in details are needed. We investigated parents' perception of policy implementation intensity; and its relationship with parents' perception of educational involution; and parents' educational anxiety, as well as the roles played by gender. Findings highlight parents who perceive a stronger policy implementation intensity experience higher levels of educational anxiety and are more likely to feel educational involution; education anxiety acts as a mediator, while gender plays a moderating role. We highlighted policy's advantages while emphasizing the necessity to avoid policy rigidity and one‐size‐fits‐all. We recommend establishing a flexible, real‐time parental feedback mechanism and promoting continuous monitoring and evaluation. This approach would enable it to meet the changing demands of education. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) poses a significant socio-economic burden globally. Existing research on HD's economic burden predominantly comes from Western settings, leaving a gap in data from Asian countries. This study aimed to assess the economic burden of HD in China and identify cost-driving factors. Methods: This study used data from a 2019 nationwide cross-sectional survey of individuals affected by rare diseases in China. Data included socio-demographic characteristics, income, disease stage, health and social insurance coverage status, treatment-seeking behaviour, and costs. Logistic regression and linear regression were used to explore potential contributors to treatment-seeking behaviour and associated costs. Results: Of the 269 individuals with HD included in this study, 80.6% were actively seeking treatment. The average annual direct medical cost, direct non-medical cost, and indirect cost were 3,265.65, 805.82, and 801.97 Euros, respectively. Compared to participants with early-stage HD, those with middle- or advanced-stage HD reported higher direct medical costs (coefficient 1,612.70, 95% confidence interval [CI]: [141.92, 3,083.48] and 2,398.58, 95% CI: [791.16, 4,006.00], respectively). However, the disease stage was not significantly associated with direct non-medical costs or indirect costs. Conclusions: This study provides crucial insights into the economic burden of HD in China. It emphasises a need for targeted policies that better cater to the financial needs of HD patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke in China, but the prevalence and prognosis of asymptomatic ICAD detected using high‐resolution magnetic resonance imaging (HR‐MRI) is largely unknown. The aim of this study was to investigate the prevalence and prognosis in order to guide neurologists in interpreting ICAD detected on HR‐MRI. Methods: We included stroke‐free participants from a community‐based prospective cohort (Shunyi study participants) who underwent HR‐MRI between July 2014 and April 2016. The participants were divided into two groups: those with or without ICAD (ICAD+ and ICAD−, respectively). ICAD included intracranial artery stenosis and non‐stenotic plaque. The primary outcome was ischemic stroke. Cox proportional hazard models were used to evaluate the association between ICAD and event outcomes. Results: A total of 1060 stroke‐free participants evaluated by HR‐MRI were included from the Shunyi study. The median age at HR‐MRI was 56 years and 64.7% were female. The ICAD prevalence was 36.3% (n = 385). The ICAD+ group was older and had more cerebrovascular risk factors. The rates of ischemic stroke in the ICAD− and ICAD+ groups were 1.3% (n = 9) and 5.2% (n = 20), respectively, with a median follow‐up time of 54 months. ICAD was associated with an increased risk of ischemic stroke in the unadjusted and adjusted Cox models, with hazard ratios of 4.12 (95% confidence interval [CI] 1.87–9.05) and 2.50 (95% CI 1.05–5.94), respectively. The greatest risk of an event outcome was observed in participants with ≥70% stenosis or occlusion. The features of high‐risk plaques were also identified. Conclusions: We found that ICAD detected using HR‐MRI increases the long‐term risk of a first‐ever ischemic stroke in a stroke‐free population, suggesting that the current primary prevention protocol of stroke awaits further optimization. [ABSTRACT FROM AUTHOR]

Background: Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing. Methods: A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing. Results: A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4–76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3–80.1]), followed by the Central (75.9% [95% CI: 74.9–76.9]) and Western regions (71.9% [95% CI: 70.7–73.1]). More than 90% (94.1% [95%CI: 93.4–94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6–60.0]). Physicians' departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were "Whole-exome sequencing (Proband)" and "Whole-exome sequencing (families of three or more)". Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers. Conclusion: Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions. [ABSTRACT FROM AUTHOR]

Background: Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China's national database of rare diseases during the same period. Results: A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories. Conclusion: Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies. [ABSTRACT FROM AUTHOR]

Objectives: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. Methods: Patients having TG levels (5.6–22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). Results: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. Conclusions: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population. [ABSTRACT FROM AUTHOR]

Background: Currently, survival benefit of immunotherapy in advanced non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first‐line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real‐world evidence. Patients and Methods: A retrospective real‐world study was conducted to evaluate clinical outcomes of chemotherapy alone (C), chemotherapy plus ICI (C + I), or chemotherapy plus angiogenesis inhibitors (C + A) as first‐line strategies for advanced NSCLC patients with EGFR ex20ins. Investigator‐assessed response and survival outcomes were compared between subgroups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to reveal concomitant alterations and explore the molecular landscape of ex20ins. Results: A total of 164 patients were screened, identifying 35 kinds of ex20ins, and 122 cases treated with C, C + I, and C + A were finally included in the first‐line analysis. C + A achieved much better objective response rate (ORR, 38.1% vs. 18.2%) and significant progression‐free survival (PFS) benefit compared with C (median, 7.73 vs.5.93 months, HR = 0.60, 95% CI: 0.40–0.90, p = 0.014), and it showed similar ORR (38.1% vs. 40.0%), but higher disease control rate (DCR, 96.8% vs. 80.0%) and numerically longer median PFS (7.73 vs. 6.53 months, HR = 0.83, 95% CI: 0.44–1.56, p = 0.30) than C + I. There was no PFS difference between C + I and C, despite of PD‐L1 expression or tumor mutational burden. KEGG analysis revealed concomitant upregulation of PI3K/AKT signaling might mediate intrinsic resistance to ICI in ex20ins. Conclusion: First‐line chemotherapy plus angiogenesis inhibitors might yield more survival benefits than chemotherapy alone for NSCLC with EGFR ex20ins, whereas, it suggests that chemotherapy in combination with ICI might not obtain a better survival benefit for this subset of patients. Activation of PI3K/AKT signaling might mediate intrinsic immunosuppression in NSCLC with EGFR ex20ins. [ABSTRACT FROM AUTHOR]

Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues. We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence. We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system. This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use. [ABSTRACT FROM AUTHOR]

To explore the impacts of household solid fuel use for cooking and heating on diabetes and fasting blood glucose (FBG) levels, we used data from the China Health and Retirement Longitudinal Study, a national survey including middle-aged and older adults. Multivariable logistic and linear regression models were used to explore the relationship between household solid fuel use (coal, crop residue, and wood) for cooking and heating with diabetes and FBG levels. Subgroup analyses were also performed based on age, sex, region of residence, smoking status, and body mass index to examine potential interactions between the variables and household solid fuel use. Among the 6195 participants, 75.4% and 61.4%, respectively, used solid fuels for heating and cooking. Relative to clean fuel users, solid fuel users had higher odds of diabetes (heating: OR, 1.21; 95% CI, 1.01–1.44; cooking: OR, 1.31; 95% CI, 1.12–1.53) and higher FBG levels (heating: β = 3.23; 95% CI, 1.10–5.36; cooking: β = 2.86; 95% CI, 0.95–4.77). Simultaneous use of solid fuels for cooking/heating was also positively associated with diabetes (OR, 1.31; 95% CI, 1.07–1.61) and FBG (β = 4.30; 95% CI, 1.82–6.78). No significant interactions were detected between subgroup variables and the impacts of solid fuel use on diabetes and FBG. Household solid fuel use is positively associated with diabetes and FBG levels. These findings imply that inhibiting household solid fuel use may contribute to decreasing diabetes development in China. [ABSTRACT FROM AUTHOR]

Background: There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it's important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China's First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China.Methods: Framework of China's national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China's First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered.Results: The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64/74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban-rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 39.4% and 32.3%, respectively, which had increased but were still at a low level.Conclusions: China's national system for rare diseases has made great progress in orphan drug access, indicating that it's been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis (hATTR) is a progressive and fatal disease with heterogenous clinical presentations, limited diagnosis and poor prognosis. This retrospective analysis study aimed to report the genotypes and phenotypes of herediary transthyretin amyloidosis (hATTR) in Chinese through a systematic review of published literature.Methods: The systematic review included structured searches of peer-reviewed literature published from 2007 to 2020 of following online reference databases: PubMed, Web of Science and the literature database in China. Extracted data included sample size, personal information (sex, age, natural course, family history), mutation type, clinical milestones and reason of death.Results: We described 126 Chinese patients with hereditary transthyretin amyloidosis identified through a systematic review of 30 studies. The most common genotype in the Chinese population was Gly83Arg (25, 19.8%), which most likely presented visual and neurological abnormalities without reported death. The second and third most common genotypes were Val30Met (20, 15.9%) and Val30Ala (10, 7.9%). Peripheral neurological manifestations (91, 72%) were dominant in 126 patients. The followed manifestation was autonomic neurological abnormalities (73, 58%). Half of the cases were reported to have visual disorders, and nearly one-third of the cases presented cardiac abnormalities. Among all 126 reported patients, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. In addition. Chinese patients were mostly early onset, with age of onset at 41.8 (SD: 8.9) years, and the median time from onset to death was 7.5 [IQR: 5.3] years. Patients with cardiac involvement had a shorter survival duration (log Rank (Mantel-Cox), χ2 = 26.885, P < 0.001).Conclusions: This study focused on 126 Chinese hATTR patients obtained from a literature review. A total of 26 kinds of TTR mutations were found and the most common one was Gly83Arg. As for phenotype, 46.03% were classified as neurological type, 30.16% as mixed type and only 2.38% as cardiac type. Chinese hATTR patients were mostly early onset (AO 41.8 years), and the median time from onset to death was 7.5 years. [ABSTRACT FROM AUTHOR]

Background: Ivabradine improves cardiac function and clinical outcomes in chronic heart failure (HF) by reducing heart rate (HR), but there is a lack of real-world data on its effectiveness and safety in Chinese patients. Methods: We designed a prospective, multicenter, observational study of Chinese adults with HF and left ventricular systolic dysfunction, resting HR ≥ 75 beats per minute (bpm), and an indication for ivabradine treatment. An interim analysis was performed using a cut-off date of 31 October 2019. The primary outcome was change in HR at 6 months after the initiation of ivabradine. Secondary endpoints included change in New York Heart Association (NYHA) functional class; quality of life (QoL), measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ); and adverse events (AEs). Results: Overall, 655 subjects were included in the interim analysis. Mean reduction in HR from baseline was 13.2 (95% confidence interval [CI] 11.2–15.2) bpm at Month 1, and 14.5 (95% CI 11.8–17.2) bpm at Month 6 (p < 0.001 for both changes). NYHA functional class and KCCQ scores improved significantly over time (p < 0.001 for all comparisons with baseline), indicating amelioration of symptoms and better QoL, respectively. Forty-four subjects (6.7%) reported a total of 60 ivabradine-related AEs, most frequently phosphenes and bradycardia (both n = 6, 0.9%). Conclusion: Treatment with ivabradine for 6 months effectively reduced HR and improved functional class and QoL in Chinese patients with chronic HF. Treatment was well tolerated. Clinical Trial Registration: ISRCTN11703380; registered on 8 November 2016. [ABSTRACT FROM AUTHOR]

Background: China has made tremendous progresses in serving the needs of its people living with rare diseases in the past decade, especially over the last 5 years. The Chinese government's systematic approach included a series of coordinated initiatives, amongst these are: forming the Rare Disease Expert Committee (2016), funding the "Rare Diseases Cohort Study" (2016-2020), and publishing its first "Rare Disease Catalog" (2018). Herein, we present the National Rare Diseases Registry System (NRDRS)-China's first national rare diseases registry, and the analysis of cases registered in the first 5 years ending Dec 31, 2020.Results: The total 62,590 cases covered 166 disease/disease types, forming 183 disease cohorts. The data from nearly 22% of them (13,947 cases) is also linked to valuable biological samples. The average age of definitive diagnosis was 30.88 years; 36.07% of cases were under 18 years of age. Regional distribution analysis showed 60% of cases were from the more developed, wealthier East and North China, suggesting the local availability of quality care and patients' financial status were key access factors. Finally, 82.04% of cases were registered from the five clinical departments: Neurology, Endocrine, Hematology, Cardiovascular, and Nephrology, suggesting that either these are most affected by rare diseases, or that there were disease non-specific ascertainment factors.Conclusions: The preliminary analysis of the first 5-year's data provides unique and valuable insight on rare disease distribution in China, and higlights the directions for enhancing equity, scale and utility. [ABSTRACT FROM AUTHOR]

Background: Low‐grade fetal adenocarcinoma of the lung (L‐FLAC) is a rare subtype of lung adenocarcinoma with undetermined histological features and genetic abnormalities. In this study, we attempted to investigate the pathological characteristics and genomic profiles of L‐FLAC. Methods: Among 9839 cases of primary lung adenocarcinoma resected at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2011 and June 2016, three cases diagnosed with L‐FLAC were selected. An immunohistochemical profile and whole exome sequencing (WES) using tumor and normal tissues was conducted. The last follow‐up date of patients was January 2021. Results: Three cases diagnosed with L‐FLAC were finally screened, suggesting a percentage of 0.03%. All three patients were male and diagnosed as stage I following radical lobectomy. The missense variant was found to be the major gene mutation type using WES. CTNNB1 and DICER1 were the two most frequent gene mutations. All cases demonstrated positive TTF‐1 expression. In addition, two patients showed positive expression of β‐catenin (nuclear/cytoplasmic expression), CgA and Sny. Negative expression of PD‐L1 in tumor cells was observed in all three cases. One case with a relatively high tumor mutation burden (TMB) (2.18 mut/Mb) had an inferior overall survival of 11.5 months. However, the other two cases with a lower TMB (0.12 and 0.74 mut/Mb) still acquired disease‐free status up to the last follow‐up date. Conclusions: L‐FLAC has a specific molecular background which is different from lung adenocarcinoma. Furthermore, gene heterogeneity was found and might be the reason for a dramatically different prognosis in these L‐FLAC patients. [ABSTRACT FROM AUTHOR]

Background: In China, there are severe unmet medical needs of people living with rare diseases. Relatedly, there is a dearth of data to inform rare diseases policy. This is historically partially due to the lack of informatics infrastructure, including standards and terminology, data sharing mechanisms and network; and concerns over patient privacy protection. Objective: This study aims to introduce the progress of China's rare disease informatics platform and knowledgebase, and to discuss critical enablers of rare disease informatics innovation, including: data standardization; knowledgebase construction; national policy support; and multi-stakeholder participation. Methods: A systemic national strategy, delivered through multi-stakeholder engagement, has been implemented to create and accelerate the informatics infrastructure to support rare diseases management. This includes a disease registry system, together with more than 80 hospitals, to perform comprehensive research information collection, including clinical, genomic and bio-sample data. And a case reporting system, with a network of 324 hospitals, covering all mainland Chinese provinces, to further support reporting of rare diseases data. International standards were incorporated, and privacy issues were addressed through HIPAA compliant rules. Results: The National Rare Diseases Registry System of China (NRDRS) now covers 166 rare diseases and more than 63,000 registered patients. The National Rare Diseases Case Reporting System of China (NRDCRS) was primarily founded on the National Network of Rare Diseases (NNRD) of 324 hospitals and focused on real-time rare diseases case reporting; more than 400,000 cases have been reported. Based on the data available in the two systems, the National Center for Health Technology Assessment (HTA) of Orphan Medicinal Products (OMP) has been established and the expert consensus on HTA of OMP was produced. The largest knowledgebase for rare disease in Chinese has also been developed. Conclusion: A national strategy and the coordinating mechanism is the key to success in the improvement of Chinese rare disease clinical care and drug accessibility. Application of innovative informatics solutions can help accelerate the process, improve quality and increase efficiency. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy and safety of empirical anti-tuberculous therapy (ATT) in patients with massive pericardial effusion (MPE) of unknown etiology in China. In-hospital patients with MPE were assessed retrospectively. Based on thorough examination excluding neoplastic, autoimmune, and non-tuberculous infectious diseases, patients who had no evidence of tuberculosis (TB) were treated with empirical ATT (Group A) or not treated with empirical ATT (Group C), whereas those who had evidence of TB were treated with standard ATT (Group B). Clinical outcomes and mitigation of MPE were compared among the three groups to identify the effectiveness of ATT. The survival free of composite endpoint was estimated using the Kaplan-Meier method. A total of 185 eligible patients were recruited: 77 in Group A, 80 in Group B, and 28 in Group C. The average follow-up was 52.9 ± 30.7, 49.4 ± 29.7, and 51.8 ± 30.2 months for Groups A, B, and C, respectively. The incidence of composite endpoint was 23.3, 24.4, and 85.7% in Groups A, B, and C, respectively (p <.0001). However, the clinical recovery rate was greater in Group B compared with Group A (p =.027). No significant difference in the safety profile of ATT was noted between Groups A and B. MPE did not spontaneously decrease in 85.7% of patients in Group C. Empirical ATT should be considered in MPE of unknown etiology in countries with a high burden of TB. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with haemophilia in China.Methods: A total of 875 Chinese patients completed the EQ-5D-5L, SF-6D, and Haem-A-QoL questionnaires. Construct validity of the EQ-5D-5L and SF-6D dimensions and indices was assessed by testing hypotheses relating these measures to Haem-A-QoL and clinical measures. The Spearman correlation coefficient was used to assess convergent validity, and one-way analysis of variance (F statistic) was used to assess the known-groups validity (discriminatory power). The agreement between EQ-5D-5L and SF-6D indices was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot.Results: Both the EQ-5D-5L and SF-6D indices showed acceptable ceiling and floor effects. As hypothesised, both EQ-5D-5L and SF-6D were significantly correlated with Haem-A-QoL (both dimensions and overall score). EQ-5D-5L and SF-6D indices as well as EQ-VAS differentiated patients are known to differ in severity of haemophilia, bleeding status, disabling levels, and comorbidity. The F statistics in the known-groups comparisons suggested that the EQ-5D-5L was slightly more discriminative than the SF-6D. ICC (0.41) and Bland-Altman plot confirmed that the agreement between the EQ-5D-5L and SF-6D indices was poor.Conclusion: Both EQ-5D-5L and SF-6D showed satisfactory construct validity in the measurement of the HRQoL among patients with haemophilia. However, the two instruments may not be used interchangeably in this patient population due to their poor agreement and differing discriminatory power. [ABSTRACT FROM AUTHOR]

Few studies have focused on immune status and disease activity in MS patients during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to investigate immune status, COVID-19 infection, and attacks in MS patients during the pandemic. An online questionnaire about COVID-19 infection, MS attack, and MS treatment during the pandemic was administered to all 525 MS patients registered in our hospital database from January 1, 2011, to June 1, 2020. Only 384 responded, of which 361 patients could be included in the final analysis. During the pandemic, 42.1% of the 361 patients and 65.0% of the 234 patients on immunotherapies were exposed to teriflunomide. Compared to patients who didn't receive treatment, patients exposed to DMTs had significantly lower levels of neutrophils (P < 0.01) and immunoglobulin G (P < 0.01), and patients exposed to immunosuppressants had significantly lower levels of immunoglobulin G (P < 0.05). Over 80% of our patients followed effective protective measures and none of the 361 MS patients in our cohort contracted COVID-19. Patients whose treatment was disrupted had a significantly higher annualized relapse rate (ARR) during than before the pandemic (P < 0.01), while the ARR of patients with continuous treatment or without treatment remained unchanged. During the pandemic, the risk of MS attack due to treatment disruption possibly outweighs the risk of COVID-19 infection under preventive measures, and MS treatment maintenance might be necessary. [ABSTRACT FROM AUTHOR]

Context: Quality of life (QoL) continues to be impaired in acromegaly after treatment.Objective: We conducted the first nationwide survey assessing QoL status among Chinese patients with treated acromegaly and explored correlations with clinical parameters, treatment modalities, and outcomes.Design: Cross-sectional study.Setting: Survey via Chinese Association of Patients with Acromegaly (CAPA) online platform.Patients: Treated patients from CAPA.Main Outcome Measures: QoL was assessed using acromegaly QoL questionnaire (AcroQoL), 5-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), and 12-item short-form health survey questionnaire (SF-12).Results: Complete, valid questionnaires from 327 patients (mean age: 39.2 years, 61.5% females) at a mean of 10 years after treatment were included. Biochemical control was satisfied in 52.9% of these patients. The controlled patients had significantly better QoL than the uncontrolled patients in all AcroQoL dimensions, most SF-12 dimensions, and pain/discomfort and anxiety/depression dimensions of the EQ-5D-5L. Patients with either controlled or uncontrolled acromegaly had significantly worse QoL than the age- and sex-adjusted population reference in most SF-12 dimensions except for physical functioning. More acromegaly-associated symptoms and comorbidities at follow-up were independent risk factors for decreased QoL across all questionnaires. Medical treatment, especially with somatostatin analogs (SSAs), and radiotherapy were predictors of worse QoL. Female patients had lower scores of physical-related QoL than male patients.Conclusions: Our study suggests that biochemical control improved but did not normalize QoL in acromegaly. Numbers of symptoms and comorbidities at follow-up, sex, radiotherapy, and medical treatment with SSAs were factors determining QoL of patients with treated acromegaly. [ABSTRACT FROM AUTHOR]

Purpose: Acromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China. Methods: This is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform. Results: In total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were <1 year. The most common first-line therapy was surgery with a transsphenoidal (76.1%) or transcranial approach (3.2%). Somatostatin analogues or dopamine agonists were administered in 20.5% of the patients as first-line therapies and in 41.7% as adjuvant therapies. Radiotherapy was performed in 32.1% of patients, 99.3% of whom received radiotherapy as an adjuvant therapy. After a median 5-year follow-up, 46.2% achieved biochemical control. Comorbidities were reported in 88.2% of the patients at follow-up; memory deterioration and thyroid nodules were the most common. Controlled patients had greater improvements in symptoms and comorbidities during follow-up than uncontrolled patients. The annual per-capita cost-of-treatment was $11013 in 2018, with medical treatments being the largest contributor (67%). Medical insurance covered 47.2% of all treatment costs. Conclusion: This study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies. [ABSTRACT FROM AUTHOR]

A new form of mobile payment, Quick Response (QR) code, has been a popular way of paying bus fares in China since 2017. Compared with conventional payment methods, cash or IC card, QR code shows a lot of differences in response time, recognition accuracy, and payment procedure, which significantly influences the boarding service time (BST) for passengers. However, no research has considered its efficiency. This study, therefore, tries to fill this gap and investigate its influence on BST. Sufficient ride-check data were collected, and the influence of the QR code payment method on BST was examined through a set of regression models. Passengers pay the bus fare with different payment methods as their first choice; nevertheless, when the payment fails, they may transfer among them. According to the payment choice, result, and process, we introduce the first-choice-based, the last-choice-based, and the choice-transfer-based models, respectively. The scenario with delays in calling out the QR code was considered in the choice-transfer-based model. The onboard crowdedness was regarded as a categorical variable to determine the regime of the boarding process in all models. We conduct empirical analysis in Wuhan, and this study can help to identify the influence of the QR code payment method on BST, consequently, improving bus service efficiency. [ABSTRACT FROM AUTHOR]

To conserve energy, ground source heat pump (GSHP) system has been used worldwide for cooling and heating buildings, and there is a persistent concern in the performance of the system. In this study, the performances of five residential GSHP systems in Hot Summer and Cold Winter (HSCW) area in China were examined. Data were acquired through field testing, operation record and long-term monitoring. And outdoor climate parameters, water temperature characteristics, cooling load characteristics, system efficiencies and energy consumptions, heat extraction and rejection imbalance were analyzed. Field test data were used to analyze the dynamic cooling load characteristics and the energy efficiency of the heat pump units and systems. Energy consumption was statistically analyzed. The results show that the weighted average Coefficient of Performance (COP) of the heat pumps and system Energy Efficiency Ratio (EER) varied from 3.36 to 5.94 and 1.95 to 4.35, respectively. Positive correlation of high cooling load and high COP was presented. More heat extraction than rejection was found, which was relevant to domestic hot water supply. Furthermore, long-term distributions of ground side water outlet temperature were used, and the skewness and kurtosis were introduced into the quantization evaluation method. [ABSTRACT FROM AUTHOR]

• Bus bunching occurs much fewer in observations than in conventional models. • Counteraction between link and stop headway deviations can resist bus bunching. • Superposition between link and stop headway deviations destroys headway regularity. • Counteraction is more prominent than superposition with buses moving forward. • The counteraction effect owes to drivers' reactions to bus travel time deviations. Bus headway deviations are the major causes of bus bunching, which is detrimental to bus service reliability and leads to excessive waiting time for passengers. Generally, it is believed that bus bunching is an inevitable result once a service disturbance occurs, as long as the route is long enough. However, in this study, it goes as low as 5% of all trips from the empirical data, contradicting the expectation in theory. This study explores the underlying reasons for this contradiction based on empirical data from two representative bus routes in China. The results show that headway deviations on links and at stops mostly counteract with each other, constraining the occurrence of bus bunching. Under this counteraction effect, the path headway deviations remain within a stable range, normally bounded by the planned headway. It indicates that the bus system has a self-repair ability to resist headway disruptions, which explains why bus bunching happens at a considerably lower frequency in practice than in theory. We further discuss how the counteraction effect works. The insights gained from this study can shed light on preventing bus bunching and generating new ways to recover bus service regularity after a headway disruption. If we can adequately adjust the control methods to make the link and stop headway deviations counteract with each other, the bus system can automatically mitigate the headway deviations. [ABSTRACT FROM AUTHOR]

The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab significantly reduces low-density lipoprotein cholesterol (LDL-C). This study (ODYSSEY EAST) assessed the efficacy and safety of alirocumab vs ezetimibe in high cardiovascular risk patients from Asia. Patients (n = 615) from China, India, and Thailand with hypercholesterolemia at high cardiovascular risk on maximally tolerated statin were randomized (2:1) to alirocumab (75 mg every 2 weeks [Q2W]; with dose increase to 150 mg Q2W at week 12 if week 8 LDL-C was >1.81 mmol/L [>70 mg/dL]) or ezetimibe (10 mg daily) for 24 weeks. The primary efficacy endpoint was percentage change in calculated LDL-C from baseline to week 24. Safety was assessed throughout. Baseline data were similar in both groups. LDL-C levels were reduced from baseline to week 24 by 56.0% and 20.3% in the alirocumab and ezetimibe groups, respectively (P <.0001 vs ezetimibe). Overall, 18.8% of alirocumab-treated patients received a dose increase to 150 mg Q2W. At week 24, 85.1% of alirocumab-treated and 40.5% of ezetimibe-treated patients reached LDL-C <1.81 mmol/L (<70 mg/dL, P <.0001 vs ezetimibe). Treatment-emergent adverse events occurred in 68.5% of alirocumab-treated and 63.1% of ezetimibe-treated patients, with upper respiratory tract infection the most common (alirocumab: 13.3%; ezetimibe: 14.1%). Injection-site reactions occurred more frequently in alirocumab-treated patients (2.7%) than in ezetimibe-treated patients (1.0%). Alirocumab significantly reduced LDL-C vs ezetimibe in high cardiovascular risk patients from Asia and was generally well tolerated. These findings are consistent with previous ODYSSEY studies. • This study evaluated alirocumab in high cardiovascular risk patients from Asia. • Low-density lipoprotein cholesterol (LDL-C) was reduced by 56.0% with alirocumab (P <.0001 vs ezetimibe). • LDL-C <1.81 mmol/L (<70 mg/dL) was reached by 85.1% of alirocumab-treated patients. • Alirocumab was generally well tolerated. • These results are consistent with previous ODYSSEY studies. [ABSTRACT FROM AUTHOR]

The author comments on the pursuit of excellence in graduate medical education to improve the quality of clinical services in China. He explains the growing conflict between doctors and patients due to shortage of adequately educated health-care workers. The author thinks the standardisation of quality of care remains an enormous challenge for China with health facilities lacking accreditation, certification, and sharing of best practices.

Precipitable water vapor (PWV) with high spatial and temporal resolution is essential for a deeper understanding of the study area's hydrological cycle and climate change. This study uses the European Center for Medium-Range Weather Forecasts Reanalysis 5 (ERA5) PWV as auxiliary verification data and proposes a reconstruction method based on back propagation neural network (BPNN) downscaling. Combining with high temporal resolution meteorological elements, digital elevation model (DEM), location, and time, reconstructed the Fengyun-4A (FY-4A) PWV data set with high spatial and temporal resolution in China was obtained. Subsequently, using the characteristics of FY-4A PWV with DEM, location, and time, a BPNN-based correction method is proposed to correct the reconstructed FY-4A PWV using the high-precision global navigation satellite system (GNSS) PWV. The results showed that the root mean square error (RMSE), Bias, and Pearson correlation coefficient (R) of the reconstructed model with respect to the FY-4A PWV are 1.32 mm, 0 mm, and 0.99, respectively. Compared with the auxiliary verification data ERA5 PWV, the RMSE, Bias, and R of the reconstructed FY-4A PWV are 0.85 mm, 0.18 mm, and 0.99, respectively. Compared with the GNSS PWV, the RMSE of the corrected FY-4A PWV is 2.44 mm, which is 28.86% lower than that of the reconstructed FY-4A PWV, the Bias is improved from −1.46 mm to 0 mm, and the R is enhanced from 0.98 to 0.99. The reconstruction and correction method of FY-4A PWV with high spatial and temporal resolution proposed in this study dramatically improves the completeness and accuracy of FY-4A PWV in China. It lays the foundation for studying rapid changes in China's hydrological cycle and climate. • High-Resolution PWV Reconstruction using Back Propagation Neural Network (BPNN) downscaling method. • Leveraging the FY-4A PWV using high-precision GNSS PWV, resulting in significant improvements. • Enhanced Accuracy: results in a 28.86% reduction in RMSE, elimination of Bias, improved correlation coefficient (R) to 0.99. • Provides a solid foundation for in-depth investigations into rapid changes in China's hydrological cycle and climate. [ABSTRACT FROM AUTHOR]

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system. • The epidemic outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread all over the world. • Inflammatory cytokine storm was common in patients with severe COVID-19. • The immune system was impaired in critical COVID-19 patients • A timely anti-inflammation treatment at the right window time is of pivotal importance. [ABSTRACT FROM AUTHOR]

Orphaned because of low prevalence and barely recoverable medical costs, patients with rare diseases are disproportionately deprived of life-saving treatment. In China, an estimated 16·8 million patients suffer from rare diseases. This substantial burden could potentially be addressed through policies that optimise research and development, licensing, pricing, and reimbursement of orphan drugs. We aimed to review existing international orphan drug frameworks to inform policy formulation in China. Pharmaceutical legislation, regulation, or policies related to the access and regulation of orphan drugs were examined from 194 WHO member countries and six regions. Relevant policies were identified through an internet search for governmental policy documents, email contacts to national pharmacovigilance centres participating in the WHO Programme for International Drug Monitoring, and a systematic literature search from academic publication databases. English publications were searched from PubMed, MEDLINE, Embase, Web of Science, and the Cochrane Library, and the search was updated to July 31, 2019. 171 drug regulation documents from 156 countries or regions and 77 full-text academic publications were retrieved and read in full. 89 (44·5%) of 200 countries or regions had documentation on orphan drug policy. 34 subthemes from content analysis were categorised into six policy themes: orphan drug designation, marketing authorisation, safety and efficacy requirements, price regulation, incentives that encourage market access, and incentives that encourage research and development. In the past 5 years, surges in the establishment of orphan drug policy were found in non-high income countries (ie, lower-middle-income countries, upper-middle-income countries, and low-income countries). Globally, patient access to orphan drugs has been boosted by government regulatory efforts and incentives. In China, priority review and tax reduction on orphan drug regulation are being initiated, along with the establishment of a national registry system for rare diseases, which are expected to positively effect patient access to orphan drugs. However, the current drug regulatory and insurance scheme in China still needs substantial improvement to achieve the accessibility and affordability of orphan drugs across the nation. A need for solid nation-wide epidemiological data on rare diseases, orphan drug designation, and systematic policy support is timely. None. [ABSTRACT FROM AUTHOR]

Aims: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF., Methods and Results: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%)., Conclusions: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Rare diseases (RDs) affect millions of people worldwide, and these diseases can severely impact the health-related quality of life (HRQoL) of those affected. Despite this, there is a lack of research measuring HRQoL using the EQ-5D-5L, which is one of the most widely used generic preference-based instruments to measure HRQoL in populations living with RDs., Objective: This study aimed to measure HRQoL using the EQ-5D-5L in a large number of patients with various types of RDs in China, and to examine the relationship between respondents' socioeconomic characteristics and preference-based health utility scores., Methods: The data used in this study were obtained from a web-based survey conducted in China. The survey aimed to explore and understand the health and socioeconomic status of patients with RDs in China. We recruited registered and eligible members, including patients or their primary caregivers, from 33 RD patient associations to complete the questionnaires via their internal social networks. HRQoL was measured using the EQ-5D-5L utility score, which was calculated based on an established Chinese value set. Utility scores have been presented based on demographics and disease-related information. Univariate linear regression analysis was used to assess the differences in the EQ-5D-5L utility scores between subgroups., Results: A total of 12,502 respondents completed the questionnaire and provided valid responses, including 6919 self-completed respondents and 5583 proxy-completed respondents. Data from 10,102 participants over the age of 12 years were elicited for analysis. Among patients with RDs, 65.3% (6599/10,102), 47.5% (4799/10,102), 47.0% (4746/10,102), 24.8% (2506/10,102), and 18.4% (1855/10,102) reported no problems for "self-care," "usual activities," "mobility," "pain/discomfort," and "anxiety/depression," respectively. A full health state was reported by 6.0% (413/6902) and 9.2% (295/3200) of self- and proxy-completed patients, respectively. Among self-completed patients, 69.9% (4826/6902) and 50.4% (3478/6902) reported no problems for "self-care" and "usual activities," respectively, whereas only 17.7% (1223/6902) reported problems for "anxiety/depression." Proxy-completed respondents showed a higher proportion of reporting extreme problems than self-completed respondents in all 5 dimensions. The mean utility scores reported by self- and proxy-completed respondents were 0.691 and 0.590, respectively. Different types of caregivers reported different utility scores, and among them, proxy-completed (mother) respondents reported the highest mean utility score., Conclusions: The establishment of a normative profile for RD patients can facilitate patients' adaptation and assess the effectiveness of interventions to improve the HRQoL and well-being of this population. Differences between self- and proxy-completed HRQoL assessed by the EQ-5D-5L have been identified in this study. This finding highlights the importance of incorporating perspectives from both patients and their proxies in clinical practice. Further development of the patient cohort is necessary to assess long-term changes in HRQoL in the RD population., (©Richard Huan Xu, Shamay S M Ng, Nan Luo, Dong Dong, Shuyang Zhang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 31.10.2023.)

A large number of investigator-initiated clinical trials (IIT) were conducted in China, some of them should play an important supporting role in new drug development. Due to the large number, small scale and uneven quality of IIT in China, especially a big gap between the IIT and industry-sponsored trials in terms of protocol design, quality management and ethical review, many IIT can't be used to support the new drug development. Therefore, it is necessary for regulatory authorities, sponsors, research institutions, ethics committees and researchers to improve their understanding of the role of IIT. In order to support the new drug development with high-quality IIT, formulating supervising system, establishing an effective quality management system, enhancing the training of researchers and improving the ability of ethical review should be implemented effectively.
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Objectives: We aimed to provide an insight into the life of survivors of critical COVID-19 in China., Methods: We conducted an online survey and qualitative interviews among intensive care unit survivors of critical COVID-19 between November and December 2020 in Wuhan, China. Eligible participants were asked to complete the EQ-5D-5L and the Short Form 36-Item Survey, and invited to participate in a semistructured face-to-face interview. Descriptive analyses and phenomenological approach were adopted to analyse quantitative and qualitative data, respectively., Results: Of 10 survivors who completed the questionnaire, 8 participated in the interview. The mean scores±SD of EuroQol-5 Dimensions-5 Level utility and EuroQol-Visual Analogue Scale were 0.88±0.15 and 80.9±14.2, respectively. The qualitative interview identified four themes, namely poor physical health, post-traumatic stress, social stigma and family support., Conclusions: COVID-19 survivors continue fighting physical and psychological impacts. Despite strong family support, these patients are struggling with social stigma. It is a long, challenging journey to recovery for patients and society., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the profile of Chinese medical professionals with burnout symptoms at the national level and identify the association between capability well-being and burnout., Design and Setting: A cross-sectional study in a nonrandom national sample of medical staff from 6 provinces across western, central and eastern China., Participants: Physicians, medical laboratory scientists, nurses, and general practitioners aged 18 years or above who submitted a completed online questionnaire from June 2019 to January 2020 successfully ( N = 25,120)., Main Outcome Measures: The prevalence of burnout symptoms was assessed by the 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS), which consists of three domains: emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). The overall high burnout was defined as EE score ≥27 or DP score ≥10. The capability well-being was measured by the Investigating Choice Experiments Capability Measure for Adults (ICECAP-A) and the overall ICECAP-A score was calculated using the UK value set, ranging from a score of 0-1. Multivariable logistic regression analysis was used to identify the association between well-being and the overall high burnout., Results: Among the 25,120 participants, 60.8% of the participants reported at least one symptom of burnout, whereas 11.2% reported all three symptoms of burnout. In the adjusted model, ICECAP-A score was independently associated with high burnout (AOR = 0.018, 95% CI = 0.015-0.022). Medical staff who were males, with shorter working years, working in tertiary hospitals, and those with the specialties of psychiatry, intensive care, emergency medicine, internal medicine, oncology, and pediatrics were at higher risk of reporting burnout symptoms., Conclusion: The burnout symptoms were relatively common among Chinese medical staff and they were found to be independently associated with capability well-being in health professionals. Interventions should be enhanced on vulnerable groups to reduce burnout and promote well-being in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Dong, Zhang, Chen, Li, Tian, Jing and Zhang.)

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1 + cells being proximal rather than distal to TIM-3 + cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy., (© 2022. The Author(s).)

Background: There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M-cis-C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients., Methods: This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M-cis-C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib-based therapy, 23 patients received chemotherapy in combination of anti-angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs., Results: Compared to other targeted therapy, brigatinib-based therapy (median progression-free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21-0.73, p = 0.001) and chemotherapy-based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06-0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib-based therapy and chemotherapy-based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57-2.67, p = 0.58). Chemotherapy combined with anti-angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11-0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06-0.54, p = 0.001), no matter they received brigatinib-based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01-0.96, p = 0.05) or chemotherapy-based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01-0.49, p < 0.001)., Conclusion: Brigatinib-based therapy and chemotherapy plus anti-angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis-C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis-C797S mutation., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Dyslipidemia International Study II (DYSIS II)-China was conducted to determine the low-density lipoprotein cholesterol (LDL-C) goal (<1.8 mmol/L) attainment rate in patients with post-acute coronary syndrome (ACS)., Hypothesis: Compliance with treatment guideline recommendations improves the LDL-C goal attainment rate in post-ACS patients., Methods: This multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL-C goal attainment rates at admission and 6-month follow-up in patients on lipid-lowering treatment (LLT) for ≥3 months and those not on LLT (LLT-naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression., Results: The LDL-C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin-equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL-C goal attainment., Conclusions: This real-world DYSIS II study in China reports a low LDL-C goal attainment rate in post-ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real-world treatment practices and guideline recommendations., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Insidious-onset acromegaly may easily be overlooked by non-specialists of acromegaly and cause diagnostic delay. This study aims to examine the association between diagnostic delay and advice from doctors before any confirmed diagnosis and subsequent comorbidities, and elicit patient-perceived reasons for misdiagnoses., Methods: An online nationwide cross-sectional study was conducted through China Acromegaly Patient Association. Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels at diagnosis and cancerous, endocrine-metabolic, musculoskeletal, cardiovascular, respiratory, and psychiatric comorbidities were reported by patients. The association between diagnostic delay and pre-diagnostic advice from doctors as well as subsequent comorbidities after diagnosis were examined., Results: In total, 447 valid responses were collected. Overall, 58.8% patients experienced misdiagnoses, and 22.6% had diagnostic delay. Before arriving at any diagnosis, patients without treatment (adjusted odds ratio [AOR]: 3.66, 95% confidence interval [CI]: 1.30-10.33) or receiving treatment to symptoms only (AOR: 7.05, 95%CI: 4.09-12.17) had greater chance of being misdiagnosed, and hence had diagnostic delay. Patients believed insufficient specialists, limited awareness of acromegaly of non-specialists and poor doctor-patient communications were major reasons of misdiagnosis. Diagnostic delay were associated with higher GH level at diagnosis and endocrine-metabolic, musculoskeletal and cardiovascular comorbidities (all P<0.05)., Conclusions: Suboptimal pre-diagnostic advice for patients, reflecting limited awareness of acromegaly among non-specialists, may delay the diagnosis and increase comorbidities. Feedbacks on the patients' final diagnosis from specialists to non-specialists should be considered, and doctor-patient communication and clinical decision-making process should be improved. Comorbidities should be screened and monitored particularly for patients with diagnostic delay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Guo, Yu, Gao, Wang, Zhu, Xing, Zhang and Dong.)

Background: Coronary artery involvement is a severe but uncommon manifestation of polyarteritis nodosa (PAN), so clinicians have little knowledge of it. Our aim was to investigate the clinical characteristics, risk factors and outcomes of patients with PAN complicated with coronary artery lesions., Methods: Data from 145 patients with PAN who were admitted to Peking Union Medical College Hospital from January 2000 to September 2019 were retrospectively collected., Results: Nineteen patients (13.1%) had coronary artery lesions due to PAN. The age at the onset of PAN was 32.3 ± 11.8 years. There were no significant differences in common risk factors for coronary arterial atherosclerosis between the patients with coronary artery involvement and those without. Affected branches of the coronary arteries were left anterior descending branch (15 patients), right coronary artery (14 patients), and left circumflex branch (9 patients). Eleven of the 19 patients exhibited multivessel lesions. Multivariate logistic regression analysis showed that celiac artery involvement (odds ratio [OR] 3.722, 95% confidence interval [CI] 1.115-12.427; P = 0.033) and new-onset hypertension (OR 6.668, 95% CI 1.936-22.961; P = 0.003) were risk factors for coronary artery involvement in patients with PAN. Stent placement was performed for 2 patients, and in-stent restenosis occurred in 1 of those patients a year later., Conclusions: PAN with coronary artery involvement exhibits more combined involvement of arteries of other organs and more severe diseases. PAN should be considered when treating young adults with an unknown origin of coronary artery lesions. In addition to systemic immunosuppressive treatment, other measures including antiplatelet and anticoagulation therapy should be initiated; however, determining the optimal time to perform procedures such as intervention or surgery is still challenging., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations. Although the diagnostic utility of clinical genetic testing in short stature has been implicated, the genetic architecture and the utility of genomic studies such as exome sequencing (ES) in a sizable cohort of patients with short stature have not been investigated systematically. In this study, we recruited 561 individuals with short stature from two centers in China during a 4-year period. We performed ES for all patients and available parents. All patients were retrospectively divided into two groups: an isolated short stature group (group I, n = 257) and an apparently syndromic short stature group (group II, n = 304). Causal variants were identified in 135 of 561 (24.1%) patients. In group I, 29 of 257 (11.3%) of the patients were solved by variants in 24 genes. In group II, 106 of 304 (34.9%) patients were solved by variants in 57 genes. Genes involved in fundamental cellular process played an important role in the genetic architecture of syndromic short stature. Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature., Competing Interests: Conflicts of interest J.R.L. has stock ownership in 23andMe, is a paid consultant for the Regeneron Genetics Center, and is a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical genomic sequencing offered in the Baylor Genetics (BG) Laboratory (http://bmgl.com). P.L. has a professional service agreement with Baylor College of Medicine and Baylor Genetics (BG), outside the submitted work. The other authors declare no potential conflicts of interest., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Background: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE)., Methods: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE., Results: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively., Conclusions: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Background: Early-onset scoliosis (EOS), defined by an onset age of scoliosis less than 10 years, conveys significant health risk to affected children. Identification of the molecular aetiology underlying patients with EOS could provide valuable information for both clinical management and prenatal screening., Methods: In this study, we consecutively recruited a cohort of 447 Chinese patients with operative EOS. We performed exome sequencing (ES) screening on these individuals and their available family members (totaling 670 subjects). Another cohort of 13 patients with idiopathic early-onset scoliosis (IEOS) from the USA who underwent ES was also recruited., Results: After ES data processing and variant interpretation, we detected molecular diagnostic variants in 92 out of 447 (20.6%) Chinese patients with EOS, including 8 patients with molecular confirmation of their clinical diagnosis and 84 patients with molecular diagnoses of previously unrecognised diseases underlying scoliosis. One out of 13 patients with IEOS from the US cohort was molecularly diagnosed. The age at presentation, the number of organ systems involved and the Cobb angle were the three top features predictive of a molecular diagnosis., Conclusion: ES enabled the molecular diagnosis/classification of patients with EOS. Specific clinical features/feature pairs are able to indicate the likelihood of gaining a molecular diagnosis through ES., Competing Interests: Competing interests: JRL has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals and Novartis and is a coinventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis (by comparative genomic hybridisation microarray and/or single-nucleotide polymorphism arrays), clinical exome sequencing and whole-genome sequencing offered in the Baylor Genetics Laboratory (http://bmgl.com)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To derive normative carotid artery stiffness data in rural adult Chinese population-based study of ultrasound measurements of carotid elasticity by using quality arterial stiffness (QAS), and to assess the changes of relevant parameters in Chinese adults 40 years of age and older., Design: A China stroke cohort study (total number: 1586) in the northern countryside were carried out between June 2013 and April 2016, designed to investigate the risk factors of cardiovascular and age-related diseases., Setting: The present study was a cross-sectional analysis of an ongoing community-based Shunyi cohort study in China., Participants: A total of 583 participants (227 men and 356 women; aged 40-80 years) with ultrasound carotid QAS examination were retrieved from the study to analyse., Primary and Secondary Outcome Measures: Arterial stiffness parameters included diastolic diameter (Dd), pulse wave velocity (PWV), stiffness indices α and β were calculated by QAS. Other clinical indicators included physical measurements, medical histories and blood biochemical test., Results: In the entire study sample, mean Dd was 7.93±0.88 mm, mean PWV was 9.4±2.4 m/s, mean α was 7.65±5.13 and mean β was 15.53±10.29. PWV was significant higher in participants with hypertension (9.9 m/s vs 9.2 m/s in those without, p=0.002), and with diabetes (10.3 m/s vs 9.2 m/s in those without, p=0.003). PWV were significantly higher in participants with HbA1c at 5.8%-6.4% versus <5.8%, but no difference was found between subjects with glycohaemoglobin (HbA1c) at 5.8%-6.4% versus >6.4% (p=0.005, p=0.955, respectively). Age increase by every 10 years was associated with Dd increased by 0.27 mm, PWV increased by 1.2 m/s, α increased by 1.34 and β increased by 2.71. Systolic blood pressure (SBP) increase by every 10 mm Hg was associated with Dd increased by 0.15 mm, PWV increased by 0.35 m/s, α increased by 0.13 and β increased by 0.15., Conclusion: Among the participants older than 40 years, stiffness of the carotid artery had differences between hypertension and non-hypertension adults, as well as between diabetes and non-diabetes adults. Stiffness of the carotid artery also have differences between adults with HbA1c at 5.8%-6.4% versus <5.8%. Stiffness of the carotid artery increases with increasing age and increasing SBP at a range from 40 and up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic. Critically ill patients often require prolonged intubation for mechanical ventilation to support breathing; thus, the artificial airway must be managed by tracheotomy. Therefore, studies exploring appropriate and safe methods for tracheotomy that minimize the risks of nosocomial transmission are important., Methods: A retrospective analysis of the clinical characteristics of 14 critically ill patients with COVID-19, who underwent bedside tracheotomy from March to April 2020 was conducted to summarize the indications for tracheotomy and key points related to personal protective equipment and surgical procedures., Results: All 14 patients were diagnosed with COVID-19 and were critically ill. All tracheotomies were performed in the late phase of the infection course. The interval between the infection and tracheotomy was 33 days, and the median interval between intubation and tracheotomy was 25.5 days. The reverse transcription-polymerase chain reaction results of secretions from the operative incision and inside the tracheotomy tube were negative. Twelve patients improved after tracheotomy, with SpO2 levels maintained above 96%. One patient died of progressive respiratory failure; another patient died of uncontrolled septic shock. No medical staff who participated in the tracheotomy was infected., Conclusions: Tracheotomy in critically ill patients with COVID-19 who meet the indications for tracheotomy potentially represents a safer approach to manage the airway and help improve the treatment outcomes. A tracheotomy performed in the late phase of the disease has a relatively low risk of infection. Adherence to key steps in the tracheotomy procedure and donning adequate personal protection will help medical staff avoid infection., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID-19. Moreover, evaluating and treating HF patients with comorbid COVID-19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID-19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID-19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web-based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID-19 based on the available data and personal experiences of physicians from Asia, Europe and the United States., (© 2020 European Society of Cardiology.)