Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Engineered Bio-Heterojunction Confers Extra- and Intracellular Bacterial Ferroptosis and Hunger-Triggered Cell Protection for Diabetic Wound Repair.

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.

Antibacterial and Angiogenic (2A) Bio-Heterojunctions Facilitate Infectious Ischemic Wound Regeneration via an Endogenous-Exogenous Bistimulatory Strategy.

In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe-associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio-heterojunctions (bio-HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)-mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous-exogenous bistimulatory (EEB) strategy. Assisted by near-infrared irradiation, the bio-HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio-HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio-HJ platform that can serve as an effective remedy for bacterial invasion-induced ischemic wounds through the EEB strategy.

Interactions among acute respiratory viruses in Beijing, Chongqing, Guangzhou, and Shanghai, China, 2009-2019.

Background: A viral infection can modify the risk to subsequent viral infections via cross-protective immunity, increased immunopathology, or disease-driven behavioral change. There is limited understanding of virus-virus interactions due to lack of long-term population-level data. Methods: Our study leverages passive surveillance data of 10 human acute respiratory viruses from Beijing, Chongqing, Guangzhou, and Shanghai collected during 2009 to 2019: influenza A and B viruses; respiratory syncytial virus A and B; human parainfluenza virus (HPIV), adenovirus, metapneumovirus (HMPV), coronavirus, bocavirus (HBoV), and rhinovirus (HRV). We used a multivariate Bayesian hierarchical model to evaluate correlations in monthly prevalence of test-positive samples between virus pairs, adjusting for potential confounders. Results: Of 101,643 lab-tested patients, 33,650 tested positive for any acute respiratory virus, and 4,113 were co-infected with multiple viruses. After adjusting for intrinsic seasonality, long-term trends and multiple comparisons, Bayesian multivariate modeling found positive correlations for HPIV/HRV in all cities and for HBoV/HRV and HBoV/HMPV in three cities. Models restricted to children further revealed statistically significant associations for another ten pairs in three of the four cities. In contrast, no consistent correlation across cities was found among adults. Most virus-virus interactions exhibited substantial spatial heterogeneity. Conclusions: There was strong evidence for interactions among common respiratory viruses in highly populated urban settings. Consistent positive interactions across multiple cities were observed in viruses known to typically infect children. Future intervention programs such as development of combination vaccines may consider spatially consistent virus-virus interactions for more effective control.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. METHODS: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. FINDINGS: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). INTERPRETATION: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. FUNDING: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Associate factors for endoscopic submucosal dissection operation time and postoperative delayed hemorrhage of early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a treatment for early gastric cancer with the advantages of small invasion, fewer complications, and a low local recurrence rate. However, there is a high risk of complications such as bleeding and perforation, and the operation time is also longer. ESD operation time is closely related to bleeding and perforation. AIM: To investigate the influencing factors associated with ESD operation time and postoperative delayed hemorrhage to provide a reference for early planning, early identification, and prevention of complications. METHODS: We conducted a retrospective study based on the clinical data of 520 patients with early gastric cancer in the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2021. The baseline data, clinical features, and endoscopic and pathological characteristics of patients were collected. The multivariate linear regression model was used to investigate the influencing factors of ESD operation time. Logistic regression analysis was carried out to evaluate the influencing factors of postoperative delayed hemorrhage. RESULTS: The multivariate analysis of ESD operation time showed that the maximum lesion diameter could affect 8.815% of ESD operation time when other influencing factors remained unchanged. The operation time increased by 3.766% or 10.247% if the lesion was mixed or concave. The operation time increased by 4.417% if combined with an ulcer or scar. The operation time increased by 3.692% if combined with perforation. If infiltrated into the submucosa, it increased by 2.536%. Multivariate analysis of delayed hemorrhage after ESD showed that the maximum diameter of the lesion, lesion morphology, and ESD operation time were independent influencing factors for delayed hemorrhage after ESD. Patients with lesion ≥ 3.0 cm (OR = 3.785, 95%CI: 1.165-4.277), lesion morphology-concave (OR = 10.985, 95%CI: 2.133-35.381), and ESD operation time ≥ 60 min (OR = 2.958, 95%CI: 1.117-3.526) were prone to delayed hemorrhage after ESD. CONCLUSION: If the maximum diameter of the lesion in patients with early gastric cancer is ≥ 3.0 cm, and the shape of the lesion is concave, or accompanied by an ulcer or scar, combined with perforation, and infiltrates into the submucosa, the ESD operation will take a longer time. When the maximum diameter of the lesion is ≥ 3.0 cm, the shape of the lesion is concave in patients and the operation time of ESD takes longer time, the risk of delayed hemorrhage after ESD is higher.

Tumor-suppressor p53 specifically binds to miR-29c-3p and reduces ADAM12 expression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an extremely aggressive malignant tumor associated with high migratory and invasive potential. The present study intends to explore regulatory mechanism of p53/microRNA (miR)-29c-3p/A disintegrin and metalloproteinase 12 (ADAM12) axis in HCC based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. METHODS: Putative miR-29c-3p binding sites on ADAM12 3'UTR were verified by a luciferase assay. The binding affinity of p53 to miR-29c-3p was assessed based on CRISPR/Cas9 technology to construct a p53 knockout (p53-/-) HCCLM3 cell line. Furthermore, the effect of p53/miR-29c-3p/ADAM12 was assessed on maligant phenotypes in vitro and tumor formation and metastasis in nude mice. RESULTS: ADAM12 was highly expressed but miR-29c-3p was poorly expressed in HCC. miR-29c-3p inhibited migratory and invasive abilities of HCC cells by targeting ADAM12 expression. p53 was found to target and upregulate miR-29c-3p, thus downregulating ADAM12 and conferring inhibitory effect on HCC cell activities. Moreover, ADAM12 knockout or p53 overexpression reduced HCC tumor formation and metastasis, which were reversed by further silencing of miR-29c-3p. CONCLUSION: The identification of the p53/miR-29c-3p/ADAM12 axis in migration and invasion of HCC may potentially further our understanding of mechanisms underpinning HCC, and also bear translational value as novel molecular targets.

Role of social organization engagement in high-risk groups intervention against HIV/AIDS: a case study from 176 cities of China.

BACKGROUND: A high-risk prevention strategy is an effective way to fight against human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). The China AIDS Fund for Non-Governmental Organizations (CAFNGO) was established in 2015 to help social organizations intervene to protect high-risk populations in 176 cities. This study aimed to evaluate the role of social organizations in high-risk population interventions against HIV/AIDS. METHODS: This study was based on the CAFNGO program from 2016 to 2020. The collected data included the number and types of social organizations participating in high-risk group interventions and the amount of funds obtained by these organizations each year. We explored the factors influencing the number of newly diagnosed AIDS cases using a spatial econometric model. Furthermore, we evaluated the effectiveness of intervention activities by comparing the percentages of the individuals who initially tested positive, and the individuals who took the confirmatory test, as well as those who retested positive and underwent the treatment. RESULTS: Overall, from 2016 to 2020, the number of social organizations involved in interventions to protect HIV/AIDS high-risk populations increased from 441 to 532, and the invested fund increased from $3.98 to $10.58 million. The number of newly diagnosed cases decreased from 9128 to 8546 during the same period. Although the number of cities with overall spatial correlations decreased, the spatial agglomeration effect persisted in the large cities. City-wise, the number of social organizations (direct effect 19.13), the permanent resident population (direct effect 0.12), GDP per capita (direct effect 17.58; indirect effect - 15.38), and passenger turnover volume (direct effect 5.50; indirect effect - 8.64) were the major factors influencing new positive cases confirmed through the testing interventions performed by the social organizations. The initial positive test rates among high-risk populations were below 5.5%, the retesting rates among those who initially tested positive were above 60%, and the treatment rates among diagnosed cases were above 70%. CONCLUSIONS: The spatial effect of social organizations participating in interventions targeting high-risk populations funded by CAFNGO is statistically significant. Nevertheless, despite the achievements of these social organizations in tracking new cases and encouraging treatment, a series of measures should be taken to further optimize the use of CAFNGO. Working data should be updated from social organizations to CAFNGO more frequently by establishing a data monitoring system to help better track newly diagnosed AIDS cases. Multichannel financing should be expanded as well.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

Seroprevalence and dynamics of anti-SARS-CoV-2 antibodies: a longitudinal study based on patients with underlying diseases in Wuhan.

BACKGROUND: Assessing the humoral immunity of patients with underlying diseases after being infected with SARS-CoV-2 is essential for adopting effective prevention and control strategies. The purpose of this study is to analyze the seroprevalence of people with underlying diseases and the dynamic change features of anti-SARS-CoV-2 antibodies. METHODS: We selected 100 communities in Wuhan using the probability-proportional-to-size sampling method. From these 100 communities, we randomly selected households according to a list provided by the local government. Individuals who have lived in Wuhan for at least 14 days since December 2019 and were ≥ 40 years old were included. From April 9-13, 2020, community staff invited all selected individuals to the community healthcare center in batches by going door-to-door or telephone. All participants completed a standardized electronic questionnaire simultaneously. Finally, 5 ml of venous blood was collected from all participants. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. During the period June 11-13, 2020 and October 9-December 5, 2020, all family members of a positive family and matched negative families were followed up twice. RESULTS: The seroprevalence of anti-SARS-CoV-2 antibodies in people with underlying diseases was 6.30% (95% CI [5.09-7.52]), and that of people without underlying diseases was 6.12% (95% CI [5.33-6.91]). A total of 313 people were positive for total antibodies at baseline, of which 97 had underlying disease. At the first follow-up, a total of 212 people were positive for total antibodies, of which 66 had underlying disease. At the second follow-up, a total of 238 people were positive for total antibodies, of which 68 had underlying disease. A total of 219 participants had three consecutive serum samples with positive total antibodies at baseline. The IgG titers decreased significantly with or without underlying diseases (P < 0.05) within the 9 months at least, while the neutralizing antibody titer remained stable. The titer of asymptomatic patients was lower than that of symptomatic patients (baseline, P = 0.032, second follow-up, P = 0.018) in the underlying diseases group. CONCLUSION: Our research focused on the serological changes of people with and without underlying diseases in a state of single natural infection. Regardless of the underlying diseases, the IgG titer decreased significantly over time, while there was no significant difference in the decline rate of IgG between with and without underlying diseases. Moreover, the neutralizing antibody titer remained relatively stable within the 9 months at least.

Suppression of histone deacetylase 1 by JSL-1 attenuates the progression and metastasis of cholangiocarcinoma via the TPX2/Snail axis.

Histone deacetylases (HDACs) are entwined with the pathogenesis of various cancers and potentially serve as promising therapeutic targets. Herein, we intend to explore the potential role of HDAC1 inhibitor (JSL-1) in the tumorigenesis and metastasis of cholangiocarcinoma (CC) and to highlight the molecular basis of its function. As shown by bioinformatics analysis and immunohistochemical detection, high HDAC1 expression was witnessed in CC tissues relative to matched controls from patients with cholecystitis. The molecular network that HDAC1 silencing reduced the enrichment of HDAC1 and Snail on the TPX2 promoter was identified using immunoprecipitation and chromatin immunoprecipitation assays. Both short hairpin RNA (shRNA)-mediated knockdown of HDAC1 and JSL-1 treatment exhibited anti-proliferative, anti-migration and anti-invasion effects on CC cells through downregulation of TPX2. The in vivo xenograft model was developed in nude mice. Consistently, the anti-tumorigenic and anti-metastatic properties of shRNA against HDAC1 and HDAC1 inhibitor were validated in the in vivo settings. Taken together, our data supported the notion that HDAC1 inhibitor retards the initiation and development of CC via mediating the TPX2/Snail axis, highlighting the anti-tumor molecular network functioned in CC.

Enhancer of zeste homolog 2 promotes hepatocellular cancer progression and chemoresistance by enhancing protein kinase B activation through microRNA-381-mediated SET domain bifurcated 1.

Metastasis and chemoresistance are the leading causes of death in patients with hepatocellular carcinoma (HCC). microRNAs (miRNAs or miRs) may be useful as diagnostic, therapeutic and prognostic markers for HCC. In this study, we set out to investigate the possible role of miR-381 in HCC development and chemoresistance along with the related mechanism. Microarray-based gene expression profiling was carried out to analyze the expression of SET domain bifurcated 1 (SETDB1) and histone methyltransferase enhancer of zeste homolog 2 (EZH2) followed by validation in clinical HCC tissues and cells. The potential binding between miR-381 and SETDB1 was found and verified. Then, the role of SETDB1 in HCC in relation to miR-381 and protein kinase B (AKT) pathway was explored through gain- and loss-of-function approaches. After expression determination of EZH2, SETDB1, miR-381, and AKT pathway-related factors, their reactions were analyzed and their functional roles in HCC progression and chemoresistance were investigated in vitro and in vivo. SETDB1 was aberrantly upregulated in clinical HCC tissues and cells. This upregulation activated AKT pathway by promoting its tri-methylation on K64. SETDB1 promoted the proliferation, migration and chemoresistance through the AKT pathway in HCC cells. In a xenograft mouse model, SETDB1 promoted HCC cell tumorigenesis in vivo by activating the AKT pathway. Furthermore, EZH2 suppressed miR-381 by catalyzing the activity of H3K27me3 on its promoter region. In conclusion, EZH2 suppressed miR-381 expression by promoting H3K27me3 activity on its promoter region to facilitate SETDB1 expression, thereby activating the AKT pathway to promote hepatocarcinogenesis and chemoresistance.

Tumor suppressive lncRNA MEG3 binds to EZH2 and enhances CXCL3 methylation in gallbladder cancer.

Gallbladder cancer is a malignant tumor with a high mortality rate. Accumulating evidence supports that lncRNA MEG3 may halt the progression of gallbladder cancer, while the downstream mechanism is rarely studied. Thus, we aim to investigate the molecular basis of the tumor-suppressing role of lncRNA MEG3 in gallbladder cancer. The expression of lncRNA MEG3 and CXCL3 was measured in patient serum and cell lines of gallbladder cancer. The viability, apoptosis, migration, and invasion of gallbladder cancer cells were assessed following ectopic MEG3 expression, as detected by CCK-8, flow cytometry, and Transwell assays. The interaction among lncRNA MEG3, EZH2, and CXCL3 was explored through ChIP, RNA pull-down, and RIP assays. The effects of lncRNA MEG3 and CXCL3 on tumor growth were evaluated by a mouse xenograft model. lncRNA MEG3 was expressed at a low level in gallbladder cancer patient serum and cell lines, while CXCL3 was highly expressed. MEG3 overexpression repressed the malignant behaviors of gallbladder cancer cells and promoted their apoptosis. MEG3 was mainly localized in the nucleus. MEG3 bound to EZH2, and EZH2 catalyzed the H3K27 trimethylation of the CXCL3 promoter region. MEG3 downregulated CXCL3 by activating EZH2-mediated H3K27 trimethylation of CXCL3; MEG3 overexpression attenuated cancer cell malignant behaviors in vitro and suppressed tumor growth in vivo in gallbladder cancer by inhibiting CXCL3 expression. Altogether, our results indicate that lncRNA MEG3 impedes gallbladder cancer development via the EZH2-CXCL3 axis, offering potential biomarkers for gallbladder cancer management.

Tumor-derived extracellular vesicles containing long noncoding RNA PART1 exert oncogenic effect in hepatocellular carcinoma by polarizing macrophages into M2.

AIM: We explored whether tumor-derived extracellular vesicles (EVs) could deliver long noncoding RNA (lncRNA) PART1 into macrophage to orchestrate macrophage polarization in the progression of hepatocellular carcinoma (HCC). METHOD: The expression patterns of PART1, microRNA (miR)-372-3p and TLR4 were detected by RT-qPCR in the HCC tissues and HCC cells. PART1 was silenced or overexpressed in HCC cells to assess its effects on the HCC cell process. EVs were isolated from PART1-overexpressed HCC cells, and co-cultured with macrophages, and gain- and loss-of-function assays were implemented in macrophages to evaluate their role in macrophage polarization. Relationship among PART1, miR-372-3p, and TLR4 was evaluated. Effect of EV-PART1 on tumorigenicity in vivo was detected by subcutaneous tumorigenicity test in nude mice. RESULT: PART1 and TLR4 were upregulated while miR-372-3p was downregulated in HCC tissues and cells. PART1 increased HCC cell proliferation, migration, invasion, and EMT. Mechanistically, PART1 bound to miR-372-3p to downregulate its expression, whereas TLR4 was negatively targeted by miR-372-3p in the macrophages. EVs containing PART1, TLR4 overexpression, or miR-372-3p inhibition induced M2 polarization of macrophages. Also, EVs containing PART1 promoted M2 polarization of macrophages and the occurrence of HCC by affecting miR-372-3p/TLR4 axis. CONCLUSION: HCC cell-derived EVs might up-regulate TLR4 by inhibiting miR-372-3p via PART1 delivery to promote macrophage M2 polarization in HCC.

Factors for Visual Acuity Improvement After Anti-VEGF Treatment of Wet Age-Related Macular Degeneration in China: 12 Months Follow up.

Purpose: To evaluate the treatment solutions and effectiveness of intravitreal ranibizumab (RBZ) or conbercept in patients with wet age-related macular degeneration (wAMD) in a real-life setting in China. Methods: The medical records of 368 patients with wAMD who started RBZ or conbercept treatment between 1 May 2014 and 30 April 2018 were evaluated. All patients were defined on fundus angiography at baseline to determine the subtype of AMD (PCV or CNV). We report visual acuity (VA) and central retinal thickness (CRT) measurements at baseline and 12 months. Results: The average number of anti-VEGF injections was 2.1 ± 1.2. The BCVA improvement of these two groups was similar with a difference of 1.00 letter (95% CI: -1.4~3.4, p = 0.8505). At the end of the study, a BCVA increase of at least 5 letters was determined to be a satisfactory efficacy endpoint. Several factors were related to the possible improvement in the satisfactory efficacy endpoint, including female sex (OR 2.07, 95% CI 1.22~3.51), number of injections (OR 1.40, 95% CI 1.12~1.75) and VA change at the first month (OR 13.75, 95% CI 7.41~25.51). Additionally, some factors were related to the possible reduction in the satisfactory efficacy endpoint, including diabetes (OR 0.27, 95% CI 0.10~0.73) and disease history (OR 0.75, 95% CI 0.57~0.98). Conclusion: Our study demonstrates that anti-VEGF drugs can effectively improve BCVA and reduce CRT in AMD patients. Sex, number of injections, VA change at the first month, diabetes and disease history are the most important factors affecting visual acuity.

The circular RNA hsa_circ_000780 as a potential molecular diagnostic target for gastric cancer.

BACKGROUND: The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC). METHODS: Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC. RESULTS: A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19-9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC. CONCLUSIONS: The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.

The changing pattern of enteric pathogen infections in China during the COVID-19 pandemic: a nation-wide observational study.

BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

Efficacy of One-stage Paravertebral Approach using a Micro-Tubular Technique in Treating Thoracic Dumbbell Tumors.

OBJECTIVE: The aim of the present study was to investigate the feasibility and efficacy of one-stage surgical resection of thoracic dumbbell tumors using a paravertebral approach and a micro-tubular technique. METHODS: Clinical data of thoracic dumbbell tumors resected using a paravertebral approach and a micro-tubular technique (14 mm, non-expandable type) in the Department of Neurosurgery at our hospital from July 2014 to July 2019 were retrospectively analyzed. Tumors were found between T1 and T12 vertebrae. Operation time, blood loss, hospitalization, recovery of neurological function, complications, the Japanese Orthopaedic Association (JOA) score, and the visual analogue scale (VAS) score were used to evaluate clinical efficacy. RESULTS: In all 31 cases, tumors were completely resected in one operation, with a mean blood loss of 53.23 ± 33.08 mL (20-150 mL) and a mean operation time of 95.16 ± 20.31 min (60-180 min). According to the Eden classification, there were four type II cases, 16 type III cases, and 11 type IV cases. The incidence of tumors in the lower thoracic segment (T8-T12) was 51.6% (16/31 cases), while the incidences in the upper thoracic segment (T1-T4) and middle segment (T5-T8) were 25.8% (8/31 cases) and 22.6% (7/31 cases), respectively. Pathological diagnoses were schwannoma (n = 22), gangliocytoma (n = 4), metastatic tumor (n = 2), neurofibroma (n = 1), granuloma (n = 1), and lipoma (n = 1). After surgery, symptoms were relieved in all patients. VAS and JOA scores significantly improved (P < 0.001). There was no pleural or lung injury, and there were no complications, such as cerebrospinal fluid leakage. The average follow-up duration was 29 months (13-59 months), during which time no tumor recurrence or spinal instability occurred. The group of Eden type II tumors had lower JOA scores at 12 months postoperatively, longer operation times, and more estimated blood loss compared with other groups (P < 0.05). There were no significant influences on VAS scores at 12 months postoperatively and postoperative hospital stay from the different types of tumors. CONCLUSION: The paravertebral approach with a micro-tubular technique is a safe and effective minimally invasive surgical approach for thoracic dumbbell tumors that allows one-stage tumor resection using a single incision. Using this approach significantly reduces intraoperative blood loss and postoperative complications, shortens hospital stay, and reduces the rates of postoperative spinal instability.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Seasonal association between viral causes of hospitalised acute lower respiratory infections and meteorological factors in China: a retrospective study.

BACKGROUND: Acute lower respiratory infections (ALRIs) caused by respiratory viruses are common and persistent infectious diseases worldwide and in China, which have pronounced seasonal patterns. Meteorological factors have important roles in the seasonality of some major viruses, especially respiratory syncytial virus (RSV) and influenza virus. Our aim was to identify the dominant meteorological factors and to model their effects on common respiratory viruses in different regions of China. METHODS: We analysed monthly virus data on patients hospitalised with ALRI from 81 sentinel hospitals in 22 provinces in mainland China from Jan 1, 2009, to Sept 30, 2013. We considered seven common respiratory viruses: RSV, influenza virus, human parainfluenza virus, adenovirus, human metapneumovirus, human bocavirus, and human coronavirus. Meteorological data of the same period were used to analyse relationships between virus seasonality and seven meteorological factors according to region (southern vs northern China). The geographical detector method was used to quantify the explanatory power of each meteorological factor, individually and interacting in pairs, on the respiratory viruses. FINDINGS: 28 369 hospitalised patients with ALRI were tested, 10 387 (36·6%) of whom were positive for at least one virus, including RSV (4091 [32·0%] patients), influenza virus (2665 [20·8%]), human parainfluenza virus (2185 [17·1%]), adenovirus (1478 [11·6%]), human bocavirus (1120 [8·8%]), human coronavirus (637 [5·0%]), and human metapneumovirus (615 [4·8%]). RSV and influenza virus had annual peaks in the north and biannual peaks in the south. Human parainfluenza virus and human bocavirus had higher positive rates in the spring-summer months. Human metapneumovirus had an annual peak in winter-spring, especially in the north. Adenovirus and human coronavirus exhibited no clear annual seasonality. Temperature, atmospheric pressure, vapour pressure, and rainfall had most explanatory power on most respiratory viruses in each region. Relative humidity was only dominant in the north, but had no significant explanatory power for most viruses in the south. Hours of sunlight had significant explanatory power for RSV and influenza virus in the north, and for most viruses in the south. Wind speed was the only factor with significant explanatory power for human coronavirus in the south. For all viruses, interactions between any two of the paired factors resulted in enhanced explanatory power, either bivariately or non-linearly. INTERPRETATION: Spatiotemporal heterogeneity was detected for most viruses in this study, and interactions between pairs of meteorological factors were found to enhance their influence on virus variation. These findings might be helpful to guide government planning, such as public health interventions, infection control practice, and timing of passive immunoprophylaxis, and might facilitate the development of future vaccine strategies. FUNDING: National Natural Science Foundation of China, the Ministry of Science and Technology of China, and the Technology Major Project of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.