Fever clinic construction and management targeted to prevention and control of healthcare-associated respiratory viral infections in Jiangsu, China: A cross-sectional observational study.

To analyze the post-COVID-19 construction and management of fever clinics targeted to prevention and control of healthcare-associated respiratory viral infections in medical institutions at all levels in China, and to provide a basis for promoting their standardized construction, we conducted this survey on the construction of fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020. Contents of the questionnaire included the general situation of medical institutions, the construction status and future construction plans of fever clinics. We find the construction rate of fever clinic in medical institutions of Jiangsu province was 75.3%. All construction indicators, quality management systems and processes fail to fully meet the requirements of documents and standards. Jiangsu province actively promotes the construction of fever clinic layout, but there is still a gap with the construction standard. As a result, it is necessary to further promote standardized construction of fever clinic, and necessary financial input should be increased to expand all constructions of fever clinic in primary medical institutions.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Clinical Benefit, Price, and Uptake for Cancer Biosimilars vs Reference Drugs in China: A Systematic Review and Meta-Analysis.

Importance: The high cost of biologics used to treat cancer has been an increasing burden in the world. In China, the recent approval of cancer biosimilar drugs to resolve this problem is promising, but evidence of clinical benefits, price, and uptake for these drugs is still lacking. Objectives: To compare characteristics of pivotal clinical trials in China and other countries for biosimilars of bevacizumab, rituximab, and trastuzumab and investigate the efficacy or effectiveness, safety, and immunogenicity outcomes of cancer biosimilars compared with reference drugs by meta-analysis. Data Sources: For this systematic review and meta-analysis, PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for published studies from database inception to February 1, 2023, using the search topics (cancers) AND (biosimilars). Study Selection: Randomized clinical trials and cohort studies that included patients with cancer were included. Data Extraction and Synthesis: Two authors independently extracted the outcome estimates and characteristics for each study. A random-effects meta-analysis was performed to summarize the relative estimates with 95% CIs. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Main Outcomes and Measures: Clinical trial characteristics were collected for biosimilars of bevacizumab, rituximab, and trastuzumab. The relative estimates of efficacy or effectiveness (objective response rate, progression-free survival, and overall survival), safety, and immunogenicity outcomes were analyzed for biosimilars vs reference drugs. The weighted average price and uptake rate were evaluated for biosimilars relative to their reference drugs between 2015 and 2022. Results: A total of 39 RCTs (involving 18 791 patients) and 10 cohort studies (involving 1998 patients) were included. The biosimilars of bevacizumab (16 RCTs; risk ratio [RR], 0.97; 95% CI, 0.93-1.01; P = .17), rituximab (12 RCTs; RR, 1.03; 95% CI, 0.98-1.08; P = .70), and trastuzumab (9 RCTs: RR, 1.04; 95% CI, 0.97-1.12; P = .29) met equivalence with reference biologics in regard to the objective response rate. The results summarized from cohort studies were consistent with those from RCTs. In 2022, cancer biosimilars were priced at 69% to 90% of the costs for the reference drugs, and their uptake reached 54% to 83% in China. Conclusions and Relevance: This systematic review and meta-analysis indicated that cancer biosimilars provided comparable clinical benefits at lower prices compared with reference drugs. These findings suggest the potential feasibility of expediting the transition from reference drugs to biosimilars to benefit more patients with cancer.

The price, efficacy, and safety of within-class targeted anticancer medicines between domestic and imported drugs in China: a comparative analysis.

Background: Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to 2022. Methods: The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs). Findings: In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, P = 0.007) and the latest ($1222 vs. $2077, P = 0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; P = 0.24), OS gains (9.3 vs 10.6 months; P = 0.66), and ORR (57% vs 62%, P = 0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; P = 0.41) and Grade ≥3 AEs (59% vs. 57%; P = 0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes. Interpretation: The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients. Funding: This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).

Assessment of the Delay in Novel Anticancer Drugs between China and the United States: A Comparative Study of Drugs Approved between 2010 and 2021.

Access to anticancer drugs has been a critical health issue in China for many years. We retrospectively analyzed the novel anticancer drugs approved in the United States (US) between 2010 and 2021 to assess the evolving landscape of the drug lags in China by taking Japan and the European Union (EU) as comparisons. The absolute and relative lags of drug initial approval (DIA) and indication approval were calculated between China (or Japan/European Union) and the US based on the US approval date of novel agents, the duration was divided into 2010-2015 and 2016-2021. Overall, 123 (244 indications) new molecular entities (NMEs) approved in the United States were included, of which 58 (94 indications), 72 (128 indications), and 99 (170 indications) NMEs were also approved in China, Japan, and the European Union, respectively. The absolute lags of DIA and indications for approval in China improved dramatically in 2016-2021 compared with 2010-2015. Similarly, the relative DIA and indication approval lags in China decreased significantly in 2016-2021. The median review lags for DIA of China in 2016-2021 were comparable to Japan but dramatically lower than that of the European Union. Nevertheless, China had significantly longer median submission lags for DIA (28 months) in 2016-2021 than that of Japan (6 months) and the European Union (1 month). Although the absolute and relative lags of anticancer drugs in China had been initially addressed, 53% of NMEs and 61% of indications were still not approved for cancers in China compared with the United States. Therefore, China should adopt steps to further reduce drug lags.

Can environmental regulations and R&D subsidies promote GTFP in pharmaceutical industry? Evidence from Chinese provincial panel data.

Based on the panel data of 30 provinces in China's pharmaceutical industry from 2000 to 2019, this paper proposes to combine the super efficiency SBM model and GML productivity index to calculate the static and dynamic green total factor productivity (GTFP). Then, the Tobit model is adopted for regression analysis on how environmental regulations, government R&D subsidies, and their cross-terms affect the GTFP. Findings suggest that: (1) Static analysis reveals that the GTFP in China's pharmaceutical industry is markedly different among provinces and regions, and the dynamic analysis shows an upward trend from 2000 to 2019. (2) The GTFP of the pharmaceutical industry and environmental rules are connected in a U-shape. The government R&D subsidies to GTFP are positive and significant, and with the expansion of government R&D subsidies, the promotion effect of environmental regulations on GTFP is enhanced. Therefore, it is necessary to set up differentiated environmental regulations systems in different provinces and increase R&D subsidies to promote the pharmaceutical industry's green development.

Effect of evaluation timing and duration of anxiety-like behaviors induced by conditioned fear in rats: Assessment using the triple test.

The fear conditioning-based models of anxiety disorders have been widely used for assessing anxiolytic action. The triple test is an evaluation method for anxiety-like behaviors that integrates the open field, elevated plus maze, and light/dark box, which can comprehensively reflect the anxiety-like behaviors state of animals. However, there are many factors that can affect the evaluation results of anxiety-like behaviors, especially the time of day (morning or afternoon), which are often ignored by most experimental studies. Accordingly, in the present study, we first measured the anxiety-like behavior in the fear conditioning-based model rats by using the triple test in the morning and afternoon, respectively (experiment 1). In experiment 2, the anxiety-like behaviors were evaluated on the 1st, 7th, 10th and 14th day after experiencing foot shock for 4 consecutive days, respectively. The fear-conditioned rats exhibited increased anxiety-like behaviors only in the afternoon and prolonged freezing times either in the morning and afternoon. Furthermore, model rats exhibit increased anxiety-like behaviors in open field, elevated plus maze, and light/dark box on the 1st day; in open field and light/dark box on the 7th day; in elevated plus maze on the 10th day; and in light/dark box on the 14th day after the final foot shock. The results suggested that the time of day had a significant effect on anxiety-like behaviors caused by conditioned fear, and increased in the afternoon vs morning. Moreover, the lasting increased in anxiety-like behavior for 14 days was appropriated to explore the effects of long-term administration of anxiolytics.

Assessment of the breakthrough-therapy-designated drugs granted in China: A pooled analysis 2020-2022.

The implementation of China's breakthrough therapy designation (BTD) program in 2020 to accelerate drug development for serious or life-threatening diseases has attracted widespread attention. Here, we review the characteristics of BTD and its implementation in China. Overall, 78 drugs with 82 BTDs were collected from the program's inception to April 2022. The time to obtain BTD for imported new drugs was significantly faster than for domestic ones. The BTDs granted for domestic new drugs were highly concentrated in oncology. The BTD drugs can reduce clinical trial and review times compared with non-BTD drugs. The implementation of BTD is expected to expedite the development of new drugs to address unmet clinical needs in China.

Analysis of Patent and Regulatory Exclusivity for Novel Agents in China and the United States: A Cohort Study of Drugs Approved Between 2018 and 2021.

Patent and regulatory exclusivity shall constitute incentives for pharmaceutical companies to develop new drugs. This study aims to investigate the differences in the patent term extension (PTE) and regulatory exclusivity between China and the United States, and to evaluate their potential impact on the market exclusivity period of novel drugs. Small-molecule novel drugs with their first indication approved in China and the United States between 2018 and 2021 were evaluated regarding their PTE and regulatory exclusivity. The PTE length of the China-approved drugs was calculated by simulation, whereas that of the US-approved drugs was extracted from the United States Patent and Trademark Office. Thirty-two and 107 novel drugs approved in China and the United States, respectively, were included in the study. The PTE length of the US-approved drugs calculated by the China-PTE method was significantly longer than that calculated by the US-PTE method. Patent extensions should be granted for 91% of new drugs in China and 82% in the United States. The simulated median PTE length of novel drugs approved in China was significantly higher than that of the United States (5.0 vs. 2.9 years, P < 0.05). It can be expected that the implementation of the PTE policy in China would significantly extend the period of market exclusivity for novel drugs similar to that of the United States. China should fully evaluate the potential impact of the PTE policy on the market exclusivity of novel drugs and provide better incentives to the development of novel drugs in addressing unmet clinical needs when developing its regulatory exclusivity policy.

Comparative Assessment of Grassland Dynamic and Its Response to Drought Based on Multi-Index in the Mongolian Plateau.

This study applied grassland related multi-index and assessed the effects of climate change by investigating grassland responses to drought. This process was performed to study grassland vegetation dynamic accurately and evaluate the effect of drought in the Mongolian Plateau (MP). The spatial-temporal characteristics of grassland dynamic in terms of coverage (Fv), surface bareness (Fb), and net primary production (NPP) from 2000 to 2013 were explored. We implemented the maximum Pearson correlation to analyze the grassland vegetation in response to drought by using self-calibrating Palmer Drought Severity Index (scPDSI). Results show that Fv and NPP present an increasing trend (0.18 vs. 0.43). Fb showed a decreasing trend with a value of -0.16. The grassland Fv and NPP positively correlated with scPDSI, with a value of 0.12 and 0.85, respectively, and Fb was -0.08. The positive correlation between Fv and NPP accounted for 84.08%, and the positive correlation between Fv and scPDSI accounted for 93.88%. On the contrary, the area with a negative correlation between Fb and scPDSI was 57.43%. The grassland in the MP showed a recovery tendency. The increase in grassland caused by positive reaction was mainly distributed in the middle of Mongolia (MG), whereas that caused by counter response was mainly distributed in the east and west MG and northeast Inner Mongolia autonomous region of China (IM). The relevant results may provide useful information for policymakers about mitigation strategies against the inverse effects of drought on grassland and help to ease the losses caused by drought.

Major pathologic response assessment and clinical significance of metastatic lymph nodes after neoadjuvant therapy for non-small cell lung cancer.

For neoadjuvant therapy in patients with non-small cell lung cancer, the major pathologic response of primary tumors may be an assessable and reliable surrogate measure of survival. Few studies have examined the pathologic evaluation of metastatic lymph node responses and their prognostic significance. This retrospective study enrolled 336 patients with non-small cell lung cancer (squamous cell carcinoma, n = 216; adenocarcinoma, n = 120) treated with neoadjuvant therapy including chemotherapy (n = 316) and targeted therapy (adenocarcinoma, n = 20). The treatment response of the primary tumor and lymph node metastases (LNM) were pathologically assessed according to the multidisciplinary recommendations of the International Association for the Study of Lung Cancer. The relationship of overall survival (OS) and disease-free survival (DFS) with the responses of the primary tumor or LNM was analyzed. The optimal cutoff value of the residual viable tumor (%RVT) of the primary tumor was 12% for both OS (P < 0.001) and DFS (P < 0.001). The pathologic assessment identified LNM in 208 patients. The optimal %RVT cutoff value in LNM was 8% for both OS (P = 0.003) and DFS (P < 0.001). The Spearman's rank correlation coefficient between primary tumors and corresponding LNM was 0.487 for %RVT (P < 0.001), which indicated a positive correlation. On multivariable analysis, an RVT of the primary tumor ≤12% was an independent prognostic factor for improved OS (P = 0.024), whereas an RVT of LNM ≤ 8% was an independent prognostic factor for increased DFS (P = 0.018). Furthermore, in the neoadjuvant chemotherapy group, the optimal %RVT cutoff values for OS in patients with squamous cell carcinoma and adenocarcinoma in the primary tumor were 12% and 58%, respectively. Considering its convenience and operability in clinical application, a 10% threshold RVT value can be used for prognostic evaluation of LNM and primary tumors of squamous cell carcinoma histology; further studies are needed to confirm the optimal cutoff value for primary tumors of adenocarcinoma.

Assessment of the Clinical Trials Safety Profile of PD-1/PD-L1 Inhibitors Among Patients With Cancer: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Understanding the safety and adverse event profiles of PD-1/PD-L1 inhibitors is important in guiding cancer immunotherapy. Consequently, we designed this meta-analysis to evaluate the safety of PD-1/PD-L1 inhibitors in clinical trials involving cancer patients. METHODS: Four safety indicators comprising treatment-related adverse events, death, discontinuation of therapy and grades 3-5 adverse events were evaluated using the random effect model. The quality of enrolled trials was assessed using the Newcastle Ottawa Scale (NOS). RESULTS: Forty-four clinical trials were included in the final meta-analysis. Compared with chemotherapy, the risk of death due to the use of PD-1/PD-L1 inhibitors was much lower than that experienced in the control group (OR = 0.65, 95%CI: [0.47, 0.91], I2 = 0%, Z = 2.52 (P = 0.01)). Similar observations were apparent regarding the other three indicators of safety and also when the use of PD-1/PD-L1 inhibitors alone is compared with the combined use of PD-1/PD-L1 and CTLA-4. When used together with chemotherapy, PD-1/PD-L1 inhibitors increased the incidence of the adverse events as compared to the use of chemotherapy alone. Increased risks for adverse events were also noticed with the use of PD-1/PD-L1 inhibitors over the use of a placebo. CONCLUSION: The use of PD-1/PD-L1 inhibitors alone is associated with a better safety profile compared to either the use of chemotherapy or the use of PD-1/PD-L1 inhibitors with other anticancer regimens.

Effects of environmental contaminants in water resources on nonalcoholic fatty liver disease.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing rapidly in recent years, which is now estimated to be over 25%. NAFLD is one of the most common chronic liver diseases in the world. At present, with the rapid development of economy and industrialization, many chemicals are released into the environment. These chemical contaminants in the environment might cause harm to human health and result in lipid metabolism disorder during long-term exposure. Moreover, the incentive of many NAFLD cases is unknown, and the environmental risk factors of NAFLD need to be urgently identified. Hence, we focus on the impacts of several popular environmental contaminants in water environment on the development and progression of NAFLD. These contaminants mainly include microcystins (MCs), disinfection by-products (DBPs), heavy metals (HMs), dioxins and polychlorinated biphenyls (PCBs). Through analyzing a great many epidemiological and toxicological studies, we have found positive associations between NAFLD and chronic exposure to these contaminants at the environmental levels. This review may enhance the understanding of liver damage caused by environmental pollutants, which are considered as tangible environmental risk factors for NAFLD.

Whole-body MRI-based multivariate prediction model in the assessment of bone metastasis in prostate cancer.

PURPOSE: A whole-body MRI (WB-MRI) including T1, short time inversion recovery (STIR), diffusion-weighted imaging (high b value) was applied in our center for the detection of bone metastasis in prostate cancer (PCa) patients. We intended to assess the diagnostic performance of this examination. METHODS: 547 cases of PCa patients with higher risk of metastasis were referred to bone scintigraphy with SPECT/CT (BS + SPECT/CT) and whole-body MRI in Shanghai Changhai Hospital. Best valuable comparator (BVC) was applied for the final diagnosis of metastasis. A panel of radiologists interpreted the results. Decision curve analysis (DCA) and receiver operating characteristic curve (ROC) analysis were applied. RESULTS: Bone metastasis was diagnosed in 110 cases, and others were non-metastatic by BVC. The area under the receiver operating characteristic curve (AUC) was higher in WB-MRI (0.778) than BS + SPECT/CT (0.634, p < 0.001). A WB-MRI-based prediction model was established with AUC of 0.877. Internal validation showed that the predictive model was well-calibrated. The DCA demonstrated that the model had higher net benefit than the BS + SPECT/CT-based model. CONCLUSION: WB-MRI is more effective in identifying metastasis in PCa patients than BS + SPECT/CT. The prediction model combined WB-MRI with clinical parameters may be a promising approach to the assessment of metastasis.

Assessment of mitochondrial function in metabolic dysfunction-associated fatty liver disease using obese mouse models.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is characterized by deregulated hepatic lipid metabolism; however, the association between MAFLD development and mitochondrial dysfunction has yet to be confirmed. Herein, we employed high-resolution respirometry, blue native polyacrylamide gel electrophoresis-based in-gel activity measurement and immunoblot analysis to assess mitochondrial function in obesity-induced mouse models with varying degrees of MAFLD. Results showed a slight but significant decrease in hepatic mitochondrial respiration in some MAFLD mice compared to mice fed a standard diet. However, the activities and levels of mitochondrial oxidative phosphorylation complexes remained unchanged during obesity-induced MAFLD progression. These results suggest that mitochondrial function, particularly oxidative phosphorylation, was mildly affected during obesity-induced MAFLD development. Moreover, transcriptome profiling of mouse and human liver tissues with varying degrees of MAFLD revealed that the decreased activation of mitochondria-related pathways was only associated with MAFLD of a high histological grade, whereas the major regulators of mitochondrial biogenesis were not altered in mice or humans during MAFLD development. Collectively, our results suggest that impaired hepatic mitochondrial function is not closely associated with obesity-induced MAFLD. Therefore, therapeutic strategies targeting mitochondria for the treatment of MAFLD should be reconsidered.

Pretreatment albumin-to-alkaline phosphatase ratio as a prognostic indicator in solid cancers: A meta-analysis with trial sequential analysis.

BACKGROUND: Albumin-to-alkaline phosphatase ratio (AAPR), a novel and economic serum biomarker, is associated with survival in patients with cancer. This study aimed to evaluate the potential role of AAPR as a prognostic indicator of solid cancers. METHODS: This meta-analysis with trial sequential analysis of retrospective studies was designed to investigate the relationship between AAPR and overall survival (OS) in solid cancers. The meta-analysis included 5951 patients from 20 cohorts. The main predictor variable was AAPR, and the main outcome was OS. Statistical tests were performed using Stata 12.0, Revman 5.3, and R 3.6.1. RESULTS: Compared to patients with a lower AAPR, those with a higher AAPR had a better OS (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.43-0.58; p < 0.001). Subgroup analysis by tumor type indicated that a higher AAPR was associated with a better OS in non-small cell lung cancer (HR: 0.45; 95% CI: 0.26-0.78; p < 0.001), small cell lung cancer (HR: 0.60; 95% CI: 0.44-0.82; p < 0.001), hepatocellular carcinoma (HR: 0.49; 95% CI: 0.34-0.69; p < 0.001), pancreatic ductal adenocarcinoma (HR: 0.47; 95% CI: 0.31-0.71; p < 0.001), and nasopharyngeal carcinoma (HR: 0.42; 95% CI: 0.21-0.85; p = 0.016). CONCLUSION: Pretreatment AAPR may be a useful prognostic indicator in solid cancers.

[Conducting clinical studies during the epidemics of communicable diseases: perspectives of methodology and health economics].

In the setting of epidemics of communicable diseases, early initiation of epidemiological and clinical data collection and analysis and conducting relevant researches are essential to the success of epidemic containment. The coronavirus disease 2019 (COVID-19), starting initially as an epidemic in China in late 2019 and now becoming a pandemic globally, poses grave challenges to the global health care systems while also provides an opportunity for studying infectious diseases in the perspective of methodology. The authors propose the evaluation methods for case reports, randomized controlled trials (RCTs), real-world evidence studies and health economics researches during an epidemic. Case reports, which are of important value for health care workers during outbreaks of infectious diseases, should be written in standard format and style and published following a strict peer review process. RCTs provides the gold standard for evaluating the effectiveness of a given treatment for the patients from the outbreaks. We review the potential challenges faced in conducting RCTs during the outbreaks. The real-world data collected from the cases in designated hospitals allow the verification of the safety and effectiveness of the intervention measures. The data from health economics research also provide important support for optimizing communicable disease prevention and control strategies. Herein we summarize the health economics research methods, study design, and technical points during the outbreaks. We recommend that clinical research and health economics research be incorporated into the prevention and control plan and measures be taken to ensure both the standards and feasibility of these studies to improve the response capacity against outbreaks of communicable diseases.

Health Risk Assessment and Source Apportionment for Heavy Metals in a Southern Chinese Reservoir Impacted by Stone Mining Activities.

Metal contaminants in drinking water pose a potential threat to human health. Metal elements (Fe, Mn, Cu, Cr, Cd, As, and Pb) in Shanzi Reservoir, China, a drinking water source for nearby cities, were measured in 2013 and 2014. The distribution characteristics of metal elements in water were identified and a health risk assessment model was used to evaluate potential harm. Principal component analysis and cluster analysis were used to determine the main sources of metal pollutants. The results showed that Pb and As exceeded the standard at some sampling sites, whereas other metal elements met the drinking water standards. The spatial distribution of metal elements was extremely uneven and might be affected by either the geochemical environment or human activities in the study region. The total risk value of metals (5 × 10-5 a-1 ) was below the recommended value of the United States Environmental Protection Agency (USEPA), the total cancer risk was higher than the total noncancer risk, and both risks were higher for children than for adults. Arsenic was the priority control pollutant, and the priority control site was located upstream of the reservoir. Source analysis showed that Fe, Mn, and Cu were mainly from soil formation and stone mining and processing industries; Pb and As were mainly from agricultural activities, free dumping and burning of domestic garbage, and atmospheric deposition from transportation emissions; Cd was mainly from agricultural application of fertilizers and pesticides; and Cr was from the stone mining and processing industry and from the electroplating and metal manufacturing industries. Integr Environ Assess Manag 2020;16:342-352. © 2019 SETAC.

[The exploration of aerobic power and energy expenditure of Chinese rugby players].

OBJECTIVE: To explore aerobic power and energy expenditure of high level rugby players in China, which provide experimental basis for accurate training and nutritional strategy in match-play. METHODS: Eighteen master rugby players were selected as research subjects. The parameters such as VO2max, lactic aicd threshold (LT) and modify conconi test were measured respectively. The differences of energy were compared between the forward and the defender. The data were analyzed by independent sample t test. RESULTS: The VO2max(42.05±3.69 ml/min ·kg-1) of rugby players was poorer. The VO2max of the forward was 38.83±3.52 (ml/min ·kg-1), and that of the defender was 47.31±3.17 (ml/min ·kg-1),and there was significant difference between the forwards and the defenders (P＜0.05). The LT of the defenders was obviously higher than that of the forwards. Modifier conconi test had a high correlation (r = 0.772) with VO2max. The average energy consumption in the first half of the game was about(276.94±18.08)kcals, the second half was(225.58±22.86)kcals, and the second half was less than the first half (P＜0.05). CONCLUSION: The aerobic power is different between the forwards and the defenders. The power of aerobic of Chinese players is weaker than that of the foreign rugby players.

Von Economo Neurons in Behavioral Variant Frontotemporal Dementia with Underlying Alzheimer's Disease.

The selective loss of von Economo neurons has been linked to the behavioral deficits in behavioral variant frontotemporal dementia (bvFTD) but whether these neurons are affected in bvFTD patients with underlying Alzheimer's disease (AD) has yet to be established. The present study assesses the von Economo neurons in pathological AD cases clinically diagnosed with either AD or bvFTD. Our results demonstrate no significant loss of von Economo neurons in all pathological AD cases, irrespective of clinical diagnosis or co-existing Lewy body pathology. These results suggest that the behavioral deficits in patients with clinical bvFTD and underlying pathological AD are not driven by the loss of von Economo neurons.