Key Factors Influencing the Operationalization and Effectiveness of Telemedicine Services in Henan Province, China: Cross-Sectional Analysis.

BACKGROUND: Telemedicine has demonstrated its potential in alleviating the unbalanced distribution of medical resources across different regions. Henan, a province in China with a population of approximately 100 million, is especially affected by a health care divide. The province has taken a proactive step by establishing a regional collaborative platform for telemedicine services provided by top-tier provincial hospitals. OBJECTIVE: We aim to identify the key factors that influence the current operationalization and effectiveness of telemedicine services in Henan province. The insights gained from this study will serve as valuable references for enhancing the efficient operation of telemedicine platforms in low- and middle-income regions. METHODS: We analyzed service reports from the performance management system of telemedicine services in Henan province throughout 2020. Using descriptive statistics and graphical methods, we examined key influencing factors, such as management competency; device configuration; and hospital capability, capacity, and service efficacy, across hospitals at 2 different tiers. In addition, we used generalized linear models and multiple linear regression models to identify key operational factors that significantly affect the service volume and efficacy of 2 major telemedicine services, namely teleconsultation and tele-education. RESULTS: Among the 89 tier 3 hospitals and 97 tier 2 hospitals connected to the collaborative telemedicine platform, 65 (73%) and 55 (57%), respectively, have established standardized management procedures for telemedicine services. As the primary delivery method for telemedicine services, 90% (80/89) of the tier 3 hospitals and 94% (91/97) of the tier 2 hospitals host videoconferencing consultations through professional hardware terminals rather than generic computers. Teleconsultation is the dominant service type, with an average annual service volume per institution of 173 (IQR 37-372) and 60 (IQR 14-271) teleconsultations for tier 3 and tier 2 hospitals, respectively. Key factors influencing the service volume at each hospital include available funding, management competency, the number of connected upper tiers, and the number of professional staff. After receiving teleconsultations from tier 3 (65/89, 73%) and tier 2 (61/97, 63%) hospitals, patients reported significant improvements in their medical conditions. In addition, we observed that service efficacy is positively influenced by management competency, financial incentives, the number of connected upper or lower tiers, and the involvement of participating medical professionals. CONCLUSIONS: Telemedicine has become increasingly popular in Henan province, with a notable focus on teleconsultation and tele-education services. Despite its popularity, many medical institutions, especially tier 2 hospitals, face challenges related to management competency. In addition to enhancing the effectiveness of existing telemedicine services, health care decision-makers in Henan province and other low- and middle-income regions should consider expanding the service categories, such as including remote emergency care and telesurgery, which have promise in addressing crucial health care needs in these regions.

Refining prediction of stroke in sinus node dysfunction patients without atrial fibrillation using a P-combined score: a multi-centre study.

AIMS: Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS. METHODS AND RESULTS: In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell's C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort. CONCLUSION: Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

By screening the risk factors of ischaemic stroke for isolated sinus node dysfunction (sinus node dysfunction without atrial fibrillation), we developed and validated a new scoring system­P-combined score, which is a combination of an abnormal P-wave terminal force in electrocardiogram-lead V1 (PTFV1) and the CHA2DS2-VASc score. We constructed the P-combined score in the following way: abnormal PTFV1 (2 points), age (1 point for 65­74 years and 2 points for ≥75 years), sex (1 point for female), congestive heart failure (1 point), hypertension (1 point), diabetes mellitus (1 point), vascular disease (1 point), and thrombotic event (2 points). Based on our analysis, we found that the P-combined score showed a strong performance (with a C-statistic of 0.716 for 5 years), which was better than the CHA2DS2-VASc score (C-statistic of 0.678 for 5 years). We also found that the performance of the P-combined score was rigorous in an independent cohort from two external centres (with a C-statistic of 0.808 for 5 years) and outperformed the CHA2DS2-VASc score (C-statistic of 0.747 for 5 years).

In vitro potency of xeruborbactam in combination with multiple ß-lactam antibiotics in comparison with other ß-lactam/ß-lactamase inhibitor (BLI) combinations against carbapenem-resistant and extended-spectrum ß-lactamase-producing Enterobacterales.

Recently, several ß-lactam (BL)/ß-lactamase inhibitor (BLI) combinations have entered clinical testing or have been marketed for use, but limited direct comparative studies of their in vitro activity exist. Xeruborbactam (XER, also known as QPX7728), which is undergoing clinical development, is a cyclic boronate BLI with potent inhibitory activity against serine (serine ß-lactamase) and metallo-ß-lactamases (MBLs). The objectives of this study were (i) to compare the potency and spectrum of ß-lactamase inhibition by various BLIs in biochemical assays using purified ß-lactamases and in microbiological assays using the panel of laboratory strains expressing diverse serine and metallo-ß-lactamases and (ii) to compare the in vitro potency of XER in combination with multiple ß-lactam antibiotics to that of other BL/BLI combinations in head-to-head testing against recent isolates of carbapenem-resistant Enterobacterales (CRE). Minimal inhibitory concentrations (MICs) of XER combinations were tested with XER at fixed 4 or 8 µg/mL, and MIC testing was conducted in a blinded fashion using Clinical and Laboratory Standards Institute reference methods. Xeruborbactam and taniborbactam (TAN) were the only BLIs that inhibited clinically important MBLs. The spectrum of activity of xeruborbactam included several MBLs identified in Enterobacterales, e.g., and various IMP enzymes and NDM-9 that were not inhibited by taniborbactam. Xeruborbactam potency against the majority of purified ß-lactamases was the highest in comparison with other BLIs. Meropenem-xeruborbactam (MEM-XER, fixed 8 µg/mL) was the most potent combination against MBL-negative CRE with MIC90 values of 0.125 µg/mL. MEM-XER and cefepime-taniborbactam (FEP-TAN) were the only BL/BLIs with activity against MBL-producing CREs; with MEM-XER (MIC90 of 1 µg/mL) being at least 16-fold more potent than FEP-TAN (MIC90 of 16 µg/mL). MEM-XER MIC values were ≤8 µg/mL for >90% of CRE, including both MBL-negative and MBL-positive isolates, with FEP-TAN MIC of >8 µg/mL. Xeruborbactam also significantly enhanced potency of other ß-lactam antibiotics, including cefepime, ceftolozane, ceftriaxone, aztreonam, piperacillin, and ertapenem, against clinical isolates of Enterobacterales that carried various class A, class C, and class D extended-spectrum ß-lactamases and carbapenem-resistant Enterobacterales, including metallo-ß-lactamase-producing isolates. These results strongly support further clinical development of xeruborbactam combinations.

Implementation, service effectiveness and satisfaction with teleconsultation services in China during the COVID-19 pandemic: from the Perspective of Primary Health Care Professionals.

OBJECTIVE: This study aims to evaluate satisfaction and service effectiveness of primary hospital physicians participating in the National Telemedicine Center of China during the COVID-19 period, and to identify potential improvement suggestions. METHODS: An online questionnaire was developed to assess the impact and satisfaction of teleconsultation services. A teleconsultation manager from each of the 98 hospitals randomly invited the medical staff involved in teleconsultation to complete the online questionnaire. RESULTS: A total of 379 health care professionals responded to the online questionnaire, with a mean age of 36.74 years. Out of these respondents, 95.5% had a positive attitude towards teleconsultation during the epidemic. Only 6.6% believed that teleconsultation systems were not useful in preventing and controlling the COVID-19 pandemic. Those respondents who were very satisfied with teleconsultation participated in it 1.81 times per week averagely. Factors related to satisfaction included weekly participation frequency（P=.003）, patient data quality(P=.023), equipment operation proficiency（P=.006）, audio and video clarity and smoothness（P=.004, P=.020）, environmental satisfaction（P=.032）, and incentive measures of title promotion（P=.003）. The main challenges in teleconsultation were the lack of understanding of medical staff and the public, insufficiently advanced software and hardware equipment, and the lack of optimization of service processes. CONCLUSIONS: Primary hospital doctors demonstrate high satisfaction levels, suggesting that teleconsultation could be an effective tool for patients seeking medical care in areas under lockdown during the COVID-19 pandemic. The primary barriers to teleconsultation include lack of public understanding and unadvanced equipment. These findings should inform future efforts to establish regional telemedicine programs in the post-COVID-19 era.

A novel prognostic signature for hepatocellular carcinoma based on SUMOylation-related genes.

SUMOylation (SUMO modification) has been confirmed to play an essential role in the progression of various malignancies. As the value of SUMOylation-related genes (SRGs) in prognosis prediction of hepatocellular carcinoma (HCC) has not been explored, we aim to construct an HCC SRGs signature. RNA sequencing was utilized to identify differentially expressed SRGs. The 87 identified genes were used in Univariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) analysis to build a signature. The accuracy of the model was validated by the ICGC and GEO datasets. The GSEA revealed that the risk score was associated with common cancer-related pathways. The ssGSEA showed that NK cells in the high-risk group were significantly reduced. The sensitivities of anti-cancer drugs confirmed the sensitivity of the high-risk group to sorafenib was lower. Further, our cohort showed that risk scores were correlated with advanced grade and vascular invasion (VI). Finally, the results of H&E staining and immunohistochemistry of Ki67 showed that higher-risk patients are more malignant.

Emission characteristics of benzene series in FCC flue gas.

Benzene series are considered as air pollutants in refineries. However, the emissions of benzene series in fluid catalytic cracking (FCC) flue gas are poorly understand. In this work, we conduct stack tests on three typical FCC units. Benzene series, including benzene, toluene, xylene and ethyl benzene, are monitored in the flue gas. It shows that the coking degree of the spent catalysts affect the emissions of benzene series significantly, and there are four kinds of carbon-containing precursors in the spent catalyst. A fixed-bed reactor is used to conduct the regeneration simulation experiments, and the flue gas is monitored by TG-MS and FTIR. The emissions of toluene and ethyl benzene are mainly emitted in the early and middle stage of the reaction (250-650 °C), while the emission of benzene is mainly detected in the middle and late stage of the reaction (450-750 °C). Xylene group is not detected in the stack tests and regeneration experiments. Higher emissions of benzene series are released from the spent catalyst with lower C/H ratio during regeneration process. With the increase of oxygen content, the emissions of benzene series decrease, and the initial emission temperature is advanced. These insights can improve the refinery's awareness and control of benzene series in the future.

Telemedicine in the Battle with 2019 Novel Coronavirus Disease (COVID-19) in Henan Province, China: A Narrative Study.

Background and Objectives: Based on practical services of the Henan Province Telemedicine Center (HTCC), the purpose of this study is to investigate the design, construction, implementation, and application effect of a specific telemedicine system in response to the coronavirus disease 2019 (COVID-19). Methods: Data on COVID-19 cases from December 31, 2019, through October 17, 2022, were collected from official websites. Data and information of telemedicine services related to COVID-19 in HTCC were collected and analyzed, and relevant graphical representations were plotted. Results: All the 147 COVID-19 designated hospitals in the Henan Province were covered by the specific telemedicine system. The cities near to the Hubei Province in the south of Henan tended to be with more COVID-19 cases, where more COVID-19-related telemedicine services were conducted. For the telemedicine system, function modules, including real-time monitoring, command and dispatch, intractable cases transfer, remote guidance, and data sharing, were designed and realized to deal with COVID-19. Through the system, telemedicine services involved COVID-19 such as epidemic surveillance, emergency rescue, case discussion, diagnosis and treatment, remote ward-round, and distance education were performed. During the period between February 2 and March 3, 2020, 646 COVID-19 patients were served by the telemedicine system, with an improvement rate of 73.2%. Conclusions: Telemedicine can improve the diagnosis and treatment of COVID-19 patients, which play a helpful role in curbing the COVID-19 epidemic. Given the current global COVID-19 pandemic and the potential re-emerge of novel zoonotic pathogens in the future, the use of telemedicine would be imperative to fight against the pandemic.

Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma.

Background: The pseudouridine synthases (PUSs) have been reported to be associated with cancers. However, their involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we assess the roles of PUSs in HCC. Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. GSE36376 gene expression microarray was downloaded from the Gene Expression Omnibus (GEO). Proteomics data for an HBV-related HCC cohort was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative mRNA expression of genes in clinical tissues and cell lines. Diagnostic efficiency was evaluated by the ROC curve. Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve. Copy number variation (CNV) was analyzed using the GSCA database. Functional analysis was carried out with GSEA, GSVA, and clusterProfiler package. The tumor microenvironment (TME) related analysis was performed using ssGSEA and the ESTIMATE algorithm. Results: We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients' OS. Meanwhile, the protein expression of DKC1, PUS1, and PUS7 was also upregulated and related to poor survival. Both mRNA and protein of these PUSs were highly diagnostic of HCC. Moreover, the CNV of PUS1, PUS7, PUS7L, and RPUSD2 was also associated with prognosis. Further functional analysis revealed that PUSs were mainly involved in pathways such as genetic information processing, substance metabolism, cell cycle, and immune regulation. Conclusion: PUSs may play crucial roles in HCC and could be used as potential biomarkers for the diagnosis and prognosis of patients.

Intrinsic Antibacterial Activity of Xeruborbactam In Vitro: Assessing Spectrum and Mode of Action.

Xeruborbactam (formerly QPX7728) is a cyclic boronate inhibitor of numerous serine and metallo-beta-lactamases. At concentrations generally higher than those required for beta-lactamase inhibition, xeruborbactam has direct antibacterial activity against some Gram-negative bacteria, with MIC50/MIC90 values of 16/32 µg/mL and 16/64 µg/mL against carbapenem-resistant Enterobacterales and carbapenem-resistant Acinetobacter baumannii, respectively (the MIC50/MIC90 values against Pseudomonas aeruginosa are >64 µg/mL). In Klebsiella pneumoniae, inactivation of OmpK36 alone or in combination with OmpK35 resulted in 2- to 4-fold increases in the xeruborbactam MIC. In A. baumannii and P. aeruginosa, AdeIJK and MexAB-OprM, respectively, affected xeruborbactam's antibacterial potency (the MICs were 4- to 16-fold higher in efflux-proficient strains). In Escherichia coli and K. pneumoniae, the 50% inhibitory concentrations (IC50s) of xeruborbactam's binding to penicillin-binding proteins (PBPs) PBP1a/PBP1b, PBP2, and PBP3 were in the 40 to 70 µM range; in A. baumannii, xeruborbactam bound to PBP1a, PBP2, and PBP3 with IC50s of 1.4 µM, 23 µM, and 140 µM, respectively. Treating K. pneumoniae and P. aeruginosa with xeruborbactam at 1× and 2× MIC resulted in changes of cellular morphology similar to those observed with meropenem; the morphological changes observed after treatment of A. baumannii were consistent with inhibition of multiple PBPs but were unique to xeruborbactam compared to the results for control beta-lactams. No single-step xeruborbactam resistance mutants were obtained after selection at 4× MIC of xeruborbactam using wild-type strains of E. coli, K. pneumoniae, and A. baumannii; mutations selected at 2× MIC in K. pneumoniae did not affect antibiotic potentiation by xeruborbactam through beta-lactamase inhibition. Consistent with inhibition of PBPs, xeruborbactam enhanced the potencies of beta-lactam antibiotics even against strains that lacked beta-lactamase. In a large panel of KPC-producing clinical isolates, the MIC90 values of meropenem tested with xeruborbactam (8 µg/mL) were at least 4-fold lower than those in combination with vaborbactam at 64 µg/mL, the concentration of vaborbactam that is associated with complete inhibition of KPC. The additional enhancement of the potency of beta-lactam antibiotics beyond beta-lactamase inhibition may contribute to the potentiation of beta-lactam antibiotics by xeruborbactam.

Usage and perceptions of telemedicine among health care professionals in China.

OBJECTIVE: To explore health care professionals' usage and perceptions of telemedicine, including their experience, evaluation and attitude towards telemedicine, and the factors affecting their satisfaction, using intention, and willingness to recommend telemedicine. METHODS: A nationwide and web-based survey was conducted. Statistical charts were used to describe the usage and perceptions of telemedicine by health care professionals. And the ordinal logistic regression was applied to analyze the influencing factors. RESULTS: A total of 1349 valid questionnaires were collected. In the survey, 74.0 % of Chinese health care professionals used telemedicine once a week. The average duration of participating in telemedicine services lasted mainly 11-30 min (64.0 %). More than half (52.5 %) of participants' hospitals adopted fee subsidy measures, followed by the award for excellent evaluation (36.4 %). The majority (92.5 %) believed that telemedicine could reduce patient referral rates. More than 95 % were satisfied with telemedicine, were willing to continue, and would recommend telemedicine for patients, respectively. The main problems existing were: incomplete system equipment, insufficient timeliness, high costs, inability to reimburse medical insurance, non-standardized medical records, inadequate publicity, cumbersome processes and long waiting time. Ordinal logistic regression showed that too short service duration (≤10 min) could significantly reduce medical professionals' overall satisfaction, using intention and willingness to recommend (P = 0.026, P = 0.017 and P = 0.040 respectively), while the convenience of the operating system had a significant positive impact (P = 0.005, P = 0.003 and P = 0.001 respectively). And cost subsidy incentive and the promotion of professional titles could significantly enhance their overall satisfaction(P = 0.006, P = 0.030), using intention (P = 0.011, P = 0.001), and willingness to recommend (P = 0.040, P = 0.004). CONCLUSIONS: The usage of telemedicine is relatively insufficient. Most health care professionals have fairly positive opinions toward telemedicine. The most mentioned issues and expectations for telemedicine can be roughly divided into four categories: infrastructure, service process, charge and cost, and popularity. It is possible to improve their evaluation by improving system convenience, enhancing service punctuality, avoiding excessively short service duration and adopting incentive measures.

Comprehensive Analysis of HOX Family Members as Novel Diagnostic and Prognostic Markers for Hepatocellular Carcinoma.

BACKGROUND: The homeobox (HOX) gene family has been found to be involved in human cancers. However, its involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we comprehensively evaluated the role of HOXs in HCC. METHODS: RNA sequencing profile of TCGA-LIHC and LIRI-JP were obtained from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. Data of TCGA-LIHC methylation were downloaded from UCSC Xena. Genetic alteration data for the TCGA samples was obtained from cBioPortal and GSCA. The diagnostic efficiency was assessed using ROC curves. The prognostic significance was evaluated by the Kaplan-Meier method and Cox regression analysis. Subsequent functional analysis was performed through the clusterProfiler package. ssGSEA, ESTIMATE, and TIDE algorithms were employed to explore the relationship between HOXs and the HCC microenvironment. Finally, pRRophetic package and NCI-60 cancerous cell lines were applied to estimate anticancer drug sensitivity. RESULTS: The mRNA levels of HOXs in HCC tissues were higher than those of noncancerous tissues and were correlated with poor overall survival (OS). HOXA6, C6, D9, D10, and D13 could serve as independent risk factors for OS. Further functional analysis revealed that these five HOXs regulate the cell proliferation, cell cycle, immune response, and microenvironment composition of HCC. In addition, the aberrant expression and methylation of HOXs is of great value in the diagnosis of HCC. CONCLUSION: HOXs play crucial roles in HCC and could serve as potential markers for HCC diagnosis and prognosis.

The long-term effects of microplastics on soil organomineral complexes and bacterial communities from controlled-release fertilizer residual coating.

Controlled-release fertilizer (CRF) was applied widely in China as an efficient utilization strategy for improving grain yield and reducing the nitrogen contamination. However, it was indeterminate to know the impacts of inevitably imported plastic into the soil on sustainable development. After ten-year fixed-site experiment, the visible residual coating microplastics were separated from the soil to measure their changes, then the long-term effects of CRF application (theoretical microplastic content 0.018-0.151 g kg-1 soil) on soil architecture and bacterial communities were evaluated. Based on soil organomineral complexes (OMC) distribution experiments and soil 16S rRNA sequence analysis, residual coating microplastics had no significant impact on soil architecture and limited effects on soil bacteria, but became the specific microbial habitat. The nitrogen rate and nitrogen release mode affected sand- and silt-grade OMC, and nitrogen rate impacted soil bacteria communities. The residual coating, small inert particles, is safe for soil OMC and bacterial communities in agricultural soil. Due to the effectiveness of CRF on reducing environmental pollution, CRF is considered as a favorable measure to the sustainable agricultural development in Shandong Province, China.

FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway.

PURPOSE: The purpose of this study was to investigate the effect of FNDC5 expression levels in hepatocellular carcinoma on the phenotypic changes of macrophages in tumor tissues. METHODS: In this study, we established an in vitro co-culture system of hepatocellular carcinoma cells and macrophages. Then we performed overexpression or knockdown of FNDC5 gene in hepatocellular carcinoma cells to observe the effect of changes in FNDC5 expression level on the phenotypic changes of THP-1 macrophages. And the conclusions obtained in the in vitro assay were further validated by a subcutaneous tumorigenic nude mice model. RESULTS: Our findings suggest that elevated FNDC5 expression in hepatocellular carcinoma cells lead to an increased M2 phenotype and decreased M1 phenotype in macrophages. This effect may be achieved by elevating PPARγ levels in macrophages while decreasing NF-κB and NLRP3 levels. These changes could be reversed by using PPARγ inhibitors. CONCLUSION: We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.

Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway.

In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein-protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.

Spatio-temporal distribution characteristics of COVID-19 in China: a city-level modeling study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a pandemic. Few studies have been conducted to investigate the spatio-temporal distribution of COVID-19 on nationwide city-level in China. OBJECTIVE: To analyze and visualize the spatiotemporal distribution characteristics and clustering pattern of COVID-19 cases from 362 cities of 31 provinces, municipalities and autonomous regions in mainland China. METHODS: A spatiotemporal statistical analysis of COVID-19 cases was carried out by collecting the confirmed COVID-19 cases in mainland China from January 10, 2020 to October 5, 2020. Methods including statistical charts, hotspot analysis, spatial autocorrelation, and Poisson space-time scan statistic were conducted. RESULTS: The high incidence stage of China's COVID-19 epidemic was from January 17 to February 9, 2020 with daily increase rate greater than 7.5%. The hot spot analysis suggested that the cities including Wuhan, Huangshi, Ezhou, Xiaogan, Jingzhou, Huanggang, Xianning, and Xiantao, were the hot spots with statistical significance. Spatial autocorrelation analysis indicated a moderately correlated pattern of spatial clustering of COVID-19 cases across China in the early phase, with Moran's I statistic reaching maximum value on January 31, at 0.235 (Z = 12.344, P = 0.001), but the spatial correlation gradually decreased later and showed a discrete trend to a random distribution. Considering both space and time, 19 statistically significant clusters were identified. 63.16% of the clusters occurred from January to February. Larger clusters were located in central and southern China. The most likely cluster (RR = 845.01, P < 0.01) included 6 cities in Hubei province with Wuhan as the centre. Overall, the clusters with larger coverage were in the early stage of the epidemic, while it changed to only gather in a specific city in the later period. The pattern and scope of clusters changed and reduced over time in China. CONCLUSIONS: Spatio-temporal cluster detection plays a vital role in the exploration of epidemic evolution and early warning of disease outbreaks and recurrences. This study can provide scientific reference for the allocation of medical resources and monitoring potential rebound of the COVID-19 epidemic in China.

Application of Telemedicine Services Based on a Regional Telemedicine Platform in China From 2014 to 2020: Longitudinal Trend Analysis.

BACKGROUND: Telemedicine that combines information technology and health care augments the operational model of traditional medical services and brings new opportunities to the medical field. China promotes telemedicine with great efforts, and its practices in the deployment of telemedicine platforms and delivery of services have become important references for the research and development in this field. OBJECTIVE: Our work described in this paper focuses on a regional telemedicine platform that was built in 2014. We analyzed the system design scheme and remote consultations that were conducted via the system to understand the deployment and service delivery processes of a representative telemedicine platform in China. METHODS: We collected information on remote consultations conducted from 2015 to 2020 via the regional telemedicine platform that employs a centralized architectural system model. We used graphs and statistical methods to describe the changing trends of service volume of remote consultation, geographical and demographic distribution of patients, and waiting time and duration of consultations. The factors that affect consultation duration and patient referral were analyzed by multivariable linear regression models and binary logistic regression models, respectively. The attitudes toward telemedicine of 225 medical practitioners and 225 patients were collected using the snowball sampling method. RESULTS: The regional telemedicine platform covers all levels of medical institutions and hospitals in all 18 cities of Henan Province as well as some interprovince hospitals. From 2015 to 2020, 103,957 remote medical consultations were conducted via the platform with an annual increasing rate of 0.64%. A total of 86.64% (90,069/103,957) of medical institutions (as clients) that applied for remote consultations were tier 1 or 2 and from less-developed regions; 65.65% (68,243/103,945) of patients who applied for remote consultations were aged over 50 years. The numbers of consultations were high for departments focusing in the treatment of chronic diseases such as neurology, respiratory medicine, and oncology. The invited experts were mainly experienced doctors with senior professional titles. Year of consultation, tier of hospital, consultation department, and necessity of patient referral were the main factors affecting the duration of consultations. In surveys, we found that 60.4% (136/225) of medical practitioners and 53.8% (121/225) of patients had high satisfaction and believed that telemedicine is of vital importance for the treatment of illness. CONCLUSIONS: The development of telemedicine in China shows a growing trend and provides great benefits especially to medical institutions located in less developed regions and senior citizens who have less mobility. Cases of remote consultations are mainly for chronic diseases. At present, the importance and necessity of telemedicine are well recognized by both patients and medical practitioners. However, the waiting time needs to be further reduced to improve the efficiency of remote medical services.

QPX7728, An Ultra-Broad-Spectrum B-Lactamase Inhibitor for Intravenous and Oral Therapy: Overview of Biochemical and Microbiological Characteristics.

QPX7728 is a novel ß-lactamase inhibitor (BLI) that belongs to a class of cyclic boronates. The first member of this class, vaborbactam, is a BLI in the recently approved Vabomere (meropenem-vaborbactam). In this paper we provide the overview of the biochemical, structural and microbiological studies that were recently conducted with QPX7728. We show that QPX7728 is an ultra-broad-spectrum ß-lactamase inhibitor with the broadest spectrum of inhibition reported to date in a single BLI molecule; in addition to potent inhibition of clinically important serine ß-lactamases, including Class A and D carbapenemases from Enterobacterales and notably, diverse Class D carbapenemases from Acinetobacter, it also inhibits many metallo ß-lactamases. Importantly, it is minimally affected by general intrinsic resistance mechanisms such as efflux and porin mutations that impede entry of drugs into gram-negative bacteria. QPX7728 combinations with several intravenous (IV) ß-lactam antibiotics shows broad coverage of Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa, including strains that are resistant to other IV ß-lactam-BLI combinations, e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam and imipenem-relebactam that were recently approved for clinical use. Based on studies with P. aeruginosa, different partner ß-lactams in combination with QPX7728 may be optimal for the coverage of susceptible organisms. This provides microbiological justification for a stand-alone BLI product for co-administration with different ß-lactams. QPX7728 can also be delivered orally; thus, its ultra-broad ß-lactamase inhibition spectrum and other features could be also applied to oral QPX7728-based combination products. Clinical development of QPX7728 has been initiated.

In Vitro Activity of the Ultrabroad-Spectrum Beta-Lactamase Inhibitor QPX7728 in Combination with Multiple Beta-Lactam Antibiotics against Pseudomonas aeruginosa.

QPX7728 is an ultrabroad-spectrum beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases. QPX7728 enhances the potency of multiple beta-lactams in beta-lactamase-producing Enterobacterales and Acinetobacter spp. In this study, we evaluated the in vitro activity of QPX7728 (QPX; 8 µg/ml) combined with multiple beta-lactams against clinical isolates of Pseudomonas aeruginosa with various beta-lactam resistance mechanisms. Seven hundred ninety clinical isolates were included in this study; 500 isolates, termed a "representative panel," were selected to be representative of the MIC distribution of meropenem (MEM), ceftazidime-avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance for clinical isolates according to 2017 SENTRY surveillance data. An additional 290 selected isolates ("challenge panel") that were either nonsusceptible to MEM or were resistant to TOL-TAZ or CAZ-AVI were also tested; 61 strains carried metallo-beta-lactamases (MBLs), 211 strains were defective in the carbapenem porin OprD, and 185 strains had the MexAB-OprM efflux pump overproduced based on a phenotypic test. Against the representative panel, susceptibility for all QPX7728/beta-lactam combinations was >90%. For the challenge panel, QPX-ceftolozane (TOL) was the most active combination (78.6% susceptible) followed by equipotent QPX-piperacillin (PIP) and QPX-cefepime (FEP), restoring susceptibility in 70.3% of strains (CLSI breakpoints for the beta-lactam compound alone). For MBL-negative strains, QPX-TOL and QPX-FEP restored the MIC values to susceptibility rates in ∼90% and ∼80% of strains, respectively, versus 68% to 70% for QPX-MEM and QPX-PIP and 63% to 65% for TOL-TAZ and CAZ-AVI, respectively. For MBL-positive strains, QPX-PIP restored the MIC to susceptibility values for ∼70% of strains versus 2% to 40% for other combinations. Increased efflux and impaired OprD had various effect on QPX7728 combination depending on the partner beta-lactam tested. QPX7728 enhanced the potency of multiple beta-lactams against P. aeruginosa, with varied results according to beta-lactamase production and other intrinsic resistance mechanisms.

Characterizing the roles of pretreatment methods for model suspensions in the membrane fouling process: The case of yeast and kaolin.

Model suspensions are important substances for characterizing fouling processes to study the mechanism of membrane fouling, thus, choosing a suitable standard suspension is critical for researches on membrane fouling processes. The pretreatment methods of model suspensions have long been neglected, which can alter the physical and chemical properties and affect fouling results. This study compared four different pretreatment methods (centrifuging and drying, magnetic stirring, ultrasonic processing, and dissolving in buffer solution) and found effects on size distribution, dispersion stability, pH variation over time, and fouling properties. Among the characterization of model suspensions, different pretreatment methods led to various changes in physical and chemical properties in this study. Membrane filtration experiments showed that these four pretreatments changed the rate of membrane fouling. The results of the analysis of filtration flux for suspensions indicated that for ultrasonic processing of all suspensions and magnetic stirring of kaolin suspensions, pore blocking was the main mechanism, while cake formation was dominant for the others. Therefore, special attention should be placed on different pretreatment methods and selecting appropriate model foulants. Finally, some guidance on selecting appropriate model foulants was given in the study.

Implementation and Application of Telemedicine in China: Cross-Sectional Study.

BACKGROUND: Telemedicine has been used widely in China and has benefited a large number of patients, but little is known about the overall development of telemedicine. OBJECTIVE: The aim of this study was to perform a national survey to identify the overall implementation and application of telemedicine in Chinese tertiary hospitals and provide a scientific basis for the successful expansion of telemedicine in the future. METHODS: The method of probability proportionate to size sampling was adopted to collect data from 161 tertiary hospitals in 29 provinces, autonomous regions, and municipalities. Charts and statistical tests were applied to compare the development of telemedicine, including management, network, data storage, software and hardware equipment, and application of telemedicine. Ordinal logistic regression was used to analyze the relationship between these factors and telemedicine service effect. RESULTS: Approximately 93.8% (151/161) of the tertiary hospitals carried out telemedicine services in business-to-business mode. The most widely used type of telemedicine network was the virtual private network with a usage rate of 55.3% (89/161). Only a few tertiary hospitals did not establish data security and cybersecurity measures. Of the 161 hospitals that took part in the survey, 100 (62.1%) conducted remote videoconferencing supported by hardware instead of software. The top 5 telemedicine services implemented in the hospitals were teleconsultation, remote education, telediagnosis of medical images, tele-electrocardiography, and telepathology, with coverage rates of 86.3% (139/161), 57.1% (92/161), 49.7% (80/161), 37.9% (61/161), and 33.5% (54/161), respectively. The average annual service volume of teleconsultation reached 714 cases per hospital. Teleconsultation and telediagnosis were the core charging services. Multivariate analysis indicated that the adoption of direct-to-consumer mode (P=.003), support from scientific research funds (P=.01), charging for services (P<.001), number of medical professionals (P=.04), network type (P=.02), sharing data with other hospitals (P=.04), and expertise level (P=.03) were related to the effect of teleconsultation. Direct-to-consumer mode (P=.01), research funding (P=.01), charging for services (P=.01), establishment of professional management departments (P=.04), and 15 or more instances of remote education every month (P=.01) were found to significantly influence the effect of remote education. CONCLUSIONS: A variety of telemedicine services have been implemented in tertiary hospitals in China with a promising prospect, but the sustainability and further standardization of telemedicine in China are still far from accomplished.