Search

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare immune disorder with rapid progression and high mortality. There have been few large cohort studies comparision of pediatric and adult HLH until now. This study was designed to explore the disparity of clinical presentations and evaluate the prognosis in pediatric and adult HLH patients. Methods: Totally 525 newly diagnosed HLH patients were included and divided into 4 groups according to age: ＜6, 6-18, 18-60 and＞60 years (geriatric patients). Mann-Whitney U test, Kruskal-Wallis test, χ2 test and Bonferroni's adjustment were used to explore the difference between age groups. Overall survival (OS) was estimated by using Kaplan-Meier method. The Cox proportional hazard model was used to analyze the univariable and multivariable association between prognostic factors and OS. Results: Geriatric patients had the lowest levels of hemoglobin, platelet, albumin and the highest level of creatinine; While patients ＜6 years of age had the lowest values of fibrinogen, IgA, IgM and highest values of triglyceride. The trigger of HLH in patients＜18 years of age was mainly EBV infection. However, lymphoma and non EBV-driven infection were the more frequent drivers in patients aged 18-60 and＞60 years, respectively. Geriatric patients were associated with highest mortality (58.8%), and 5-year overall survival (OS) was 43%. By contrast, 5-year OS of patients＜6, 6-18 and 18-60 years were 86.1%, 74% and 58.9%, respectively. Additionally, among patients with different etiologies (EBV, non EBV-driven infection and uncertain causes) and treatment regimens (HLH-04, HLH-94 and glucocorticoid regimen), geriatric patients showed lowest 5-year OS. Multivariate analysis revealed that creatinine and alanine aminotransferase were independent risk factors affecting the survival of patients aged 0-6 years; While albumin and IgG were independent factors affecting survival of geriatric patients. Conclusion: Our study showed a wide heterogeneity of clinical presentations, etiology distribution, prognostic fatctors and survival outcomes in pediatric and adult HLH patients.

ImportanceThe Sabin-strain inactivated poliovirus vaccine (IPV) may be a tool for polio outbreak response in certain situations.ObjectiveTo investigate the response to a type 2 vaccine-derived poliovirus (VDPV2) outbreak.Design, Setting, and ParticipantsThis case series was conducted in China after a VDPV2 was detected in stool specimens from a child with acute flaccid paralysis (AFP) in Sichuan Province in 2019, 3 years after the global withdrawal of live, attenuated type 2 oral poliovirus vaccine (OPV). Investigation followed National Health Commission and World Health Organization guidance and included searching hospitals for unreported AFP cases; testing stool specimens from the child, his contacts, and local children; enhanced environmental surveillance for VDPV2s in wastewater; and measuring vaccination coverage. Sabin-strain IPV campaigns were conducted in a wide geographic area.Main Outcomes and MeasuresAny VDPV2 detection after completion of the supplementary immunization activities.ResultsA 28-nucleotide-change VDPV2 was isolated from a young boy. Three VDPV2s were detected in healthy children; 2 were contacts of the original child, and none had paralysis. A search of 31 million hospital records found 10 unreported AFP cases; none were polio. No type 2 polioviruses were found in wastewater. Prior to the event, polio vaccine coverage was 65% among children younger than 5 years. Sabin-strain IPV campaigns reached more than 97% of targeted children, administering 1.4 million doses. No transmission source was identified. More than 1 year of enhanced poliovirus environmental and AFP surveillance detected no additional VDPVs.Conclusions and RelevanceThese findings suggest that the circulating VPDV2 outbreak in 2019 was associated with low vaccine coverage. An investigation discovered 3 infected but otherwise healthy children and no evidence of the virus in wastewater. Following Sabin-strain IPV–only campaigns expanding from county to prefecture, the poliovirus was not detected, and the outbreak response was considered by an expert panel and the World Health Organization to have been successful. This success suggests that the Sabin-strain IPV may be a useful tool for responding to circulating VDPV2 outbreaks when high-quality supplementary immunization activities can be conducted and carefully monitored in settings with good sanitation.

In the “2030 Agenda for Sustainable Development” proposed by the United Nations, there are several Sustainable Development Goals (SDGs) related to the sustainable development of urbanization. Therefore, this paper combines remote sensing products and statistics data; uses the entropy weight method to construct a comprehensive assessment framework for the sustainable development of urbanization in Hainan Island based on 11 SDGs; and conducts a spatial and temporal analysis of Hainan Island from 2011 to 2020. The assessment scores of the study area are distributed spatially in a pattern that scores high in the north and south and low in the middle and west. In terms of SDGs’ progress, each region faces its own challenges and needs to develop under its own status. For Wuzhishan City and Ding’an County, which scored low in the assessment, newly increased fixed assets, per capita public green areas and the rate of science and technology expenditures to local government expenditures are the main factors affecting the assessment scores.

A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10

The application of fungicide mixture is one of the most important measures to extend the service life of highly selective fungicides. Pyraclostrobin (PYR), which has been extensively used to control plant diseases by inhibiting mitochondrial respiration of pathogenic fungi, is at a high risk of resistance development. In this study, the potential of PYR alone or in combination with cystamine, an inhibitor of microbial transglutaminase, to suppress Fusarium graminearum was tested in vitro and in vivo. A synergistic effect of PYR/CYS mixture was observed both in vitro and when applied to etiolated wheat coleoptile. The control effect of PYR/CYS mixture on F. graminearum was better than that of PYR alone, which was reflected by the increased protection effect. The discrepancies of membrane permeability and the redox-physiological state were observed between PYR and PYR/CYS treatments, suggesting that an increased PYR availability in F. graminearum mycelia could be related with the observed synergistic action. Moreover, a synergistic profile was observed between PYR and CYS in regard of massive autophagosomes in mycelia, indicating that enhanced autophagy could be involved in the mode of action of PYR/CYS mixture. The differential content of mitochondrial metabolites between PYR and PYR/CYS treatments also provided evidence for CYS contribution to the fungicidal action of PYR/CYS mixture. The results provide insight into the synergistic mechanism of action of PYR/CYS mixture and an effective way to enhance the efficiency of PYR to combat F. graminearum.

Objective To study the clinical efficacy, recurrence rate and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with microneedle or CO2 lattice laser (CO2FL), in comparison with intrascar betamethasone injection in the treatment of hypertrophic acne scar. Methods Fifty-two patients with hypertrophic acne scars at the mandibular angle were enrolled and assigned to different therapy groups. Sixteen patients were treated with microneedle-assisted incorporation of ALA. Twenty-eight patients underwent CO2FL-assisted incorporation of ALA. Eight patients received standard therapy with intrascar injection of glucocorticoid. Two dermatologists, blinded to the therapy groups, independently evaluated the scars in all patients using the average value of the Vancouver Scar Scale score, which was treated as an integer variable. Results After three rounds of treatment, there was no significant difference in therapeutic effective rate among the microneedle, laser and topical glucocorticoid groups (93.75% vs 100% vs 100%, P = .855). One out of 16 patients (6.25%) in the microneedle group, no patient (0%) in the laser group and two out of eight patients (25%) in the topical glucocorticoid group had recurrence. The laser group showed a higher rate of adverse effects, which were usually mild and reversible, except for pigmentation. Adverse reactions could be completely subsided within 3 weeks. Conclusions Either CO2FL or microneedle combined ALA-PDT for hypertrophic scar, as to topical glucocorticoid therapy, showed equivalent clinical effects but lower recurrence rate within 6 months of follow-up period.

In order to discover the causes of a coxsackievirus B4 (CV-B4)-associated hand, foot, and mouth disease (HFMD) outbreak and to study the evolutionary characteristics of the virus, we sequenced isolates obtained during an outbreak for comparative analysis with previously sequenced strains. Phylogenetic and evolutionary dynamics analysis was performed to examine the genetic characteristics of CV-B4 in China and worldwide. Phylogenetic analysis showed that CV-B4 originated from a common ancestor in Shandong. CV-B4 strains isolated worldwide could be classified into genotypes A-E based on the sequence of the VP1 region. All CV-B4 strains in China belonged to genotype E. The global population diversity of CV-B4 fluctuated substantially over time, and CV-B4 isolated in China accounted for a significant increase in the diversity of CV-B4. The average nucleotide substitution rate in VP1 of Chinese CV-B4 (5.20 × 10-3 substitutions/site/year) was slightly higher than that of global CV-B4 (4.82 × 10-3 substitutions/site/year). This study is the first to investigate the evolutionary dynamics of CV-B4 and its association with an HFMD outbreak. These findings explain both the 2011 outbreak and the global increase in CV-B4 diversity. In addition to improving our understanding of a major outbreak, these findings provide a basis for the development of surveillance strategies.

Hemocytes in the hemolymph of insects perform innate immunity, but systematic studies to compare immunotoxicity of pesticides on hemocytes are still few. In this study, an insect hemocyte system was used to assess the impact of pesticides with different modes of action, which included loss of cell viability, inhibition of hemophagocytosis, and reduction of nitric oxide synthase (NOS) activity. Results showed that piericidin A was the most cytotoxic to hemocytes, chlorfluazuron and hexaflumuron were the next. Also, piericidin A, chlorfenapyr, and fipronil had strong inhibitory effects on hemophagocytosis, and the effects of piericidin A and chlorfenapyr were persistent, while that of fipronil was short-lived. Moreover, fenoxycarb and hexaflumuron selectively inhibited granulocyte phagocytosis, tebufenozide only showed inhibition on plasmatocyte phagocytosis, but both inhibitory effects were transient. Furthermore, fenoxycarb and hexaflumuron showed a short-term strong inhibitory effect on the activity of NOS, chlorfenapyr and piericidin A showed a weak induction of NOS activity, while other pesticides exhibited a strong induction. Taken together, piericidin A was the most toxic and imidacloprid was the least toxic to hemocytes, and the alterations in hemocyte functions compromised immunity.

The authors have requested that this preprint be removed from Research Square.

The growing evidences of resistant fungi stimulate fully understanding tebuconazole regarding its crystal structure on fungicidal activity. In this study, the crystal structures of six technical tebuconazoles (BX, HH, JP, QZ, SJ, and YT) were characterized by using high-resolution X-ray powder diffraction and three-dimensional crystal structure modeling. A structure-activity relationship of the tebuconazoles on the susceptible (HLS and YJS) or resistant (XHR) Botrytis cinerea isolates was analyzed, the differential tricarboxylic acid (TCA) cycle metabolism was determined, and molecular docking with sterol 14α-demethylase (CYP51) was performed. The results showed that tebuconazole existed in three types of crystal forms: an overlapping-pair conformation, a side-by-side-pair conformation, and a parallel-pair conformation. QZ with the parallel-pair conformation and the minimum crystal cell volume exhibited a higher activity and a lower resistant level. XHR possessed a higher content of TCA cycle metabolites and phosphate than YJS, but the exposure to QZ significantly reduced the contents of citrate, isocitrate, α-ketoglutarate and oxaloacetate in XHR, as did the exposure to other technical tebuconazoles. Moreover, the point mutations F487L, G464S, and G443S altered the binding properties of chiral stereoscopic R-QZ with CYP51 protein. Especially the G443S mutation promoted a weak linking of R-QZ with LEU380 and TYR126, and greatly slashed the binding action at lower docking score. In conclusion, our results evidenced an efficient crystal conformation of tebuconazole to improve botryticidal activity and a potential adaptability of B. cinerea to tebuconazole inhibition in TCA cycle metabolism and CYP51 protein mutation.

Burkitt lymphoma (BL) is an aggressive Epstein-Barr virus (EBV)-driven B-cell lymphoma characterized by the translocation and rearrangement of the c-Myc proto-oncogene. High-intensity multidrug chemotherapy regimens have a limited effect on the survival of refractory or relapsed BL patients, mainly owing to the high EBV load and drug resistance. l-asparaginase ( l-Asp) and etoposide (VP-16) play a beneficial role in EBV-related lymphoproliferative diseases; however, their roles and mechanisms in BL remain unclear. In this study, we found that VP-16 inhibited BL cell proliferation and arrested the cell cycle at the G

Echovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.

Despite advancement in the treatment of diffuse large B-cell lymphoma (DLBCL), many patients tend to relapse or become refractory after initial therapy. Therefore, it is essential to identify novel therapeutic targets and drugs, understand the molecular pathogenesis mechanism of DLBCL, and find ways to prevent and treat relapsed or refractory DLBCL. BIX-01294 is a small molecule compound that specifically inhibits EHMT2 activity. In this study, we demonstrate that BIX-01294 triggered the inhibition of human DLBCL cell proliferation, lead to G1 phase arrest via increasing P21 level and reducing cyclin E level. BIX-01294 also induced apoptosis via endogenous and exogenous apoptotic pathways. Moreover, BIX-01294 triggered autophagy and activated ER stress in human DLBCL cells. Furthermore, we showed that both key components of ER stress, ATF3, and ATF4, are required for BIX-01294-induced apoptosis and autophagy. Hence, this study provides new evidence that EHMT2 may be a new therapeutic target, and BIX-01294 may be a potential therapeutic drug for treating DLBCL.

Objective. This systematic review was able to evaluate the clinical evidence of JSBC in the randomized controlled trial (RCT) of diabetic nephropathy. Methods. The Chinese and English literatures published in PubMed, Cochrane Library, VIP, Wanfang Data, CNKI, and CBM before July 30, 2019, were retrieved. This study includes only randomized controlled trials of treatments related to diabetic nephropathy. We assessed the methodological quality of the subjects involved according to the assessment criteria in 5.3.3 of the Cochrane Assessment Manual. RevMan 3.5.5 software was used to analyze the relevant data, meta-analysis, and inverted funnel analysis chart. Results. This study included 26 RCTs, including 4676 patients in total (2342 cases in the experimental group and 2334 cases in the control group). The results of 8 randomized controlled trials showed that urinary microprotein excretion rate (UAER) significantly decreased ( P < 0.0001 ) before and after treatment of diabetic nephropathy. Conclusion. The available clinical evidence has suggested that JSBC combined with western drugs is differentially effective in the treatment of diabetic nephropathy. The combination of JSBC with western medicine is more effective. However, due to the small amount and low quality of the included literatures, the current evidence is not certain to be fully clinically applicable.

Magnetic molecular imprinted polymers (MIPs) based on 4-vinylbenzyltrimethylammonium chloride (VBTAC) and 4-vinylbenzoic acid (VBA) deep eutectic solvent as dual functional monomers was successfully synthesized for the specific recognition of laminarin. The MIPs were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, thermal gravimetric analysis, and vibrating sample magnetometer analysis. The results showed that the MIPs were spheres of a uniform size, with the surface rich in cavities and excellent superparamagnetism properties. The adsorption experiments showed that MIPs conform to pseudo-second-order kinetics and Langmuir isotherm adsorption. The maximum adsorption capacity under optimal conditions was 322.58 μg·mg

Purpose Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Methods Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously. Results Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P = .007 and .002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Conclusions Coadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178., In this study, we confirmed that combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy strategy was efficient (81% ORR and 52.4% CR respectively) for R/R DLBCL, and that the toxicities was transient and manageable. To our knowledge, this is the first report that combination of anti‐CD19 and anti‐CD20 double‐target CAR‐T cell therapy for R/R DLBCL, and our data demonstrated the feasibility of combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy for R/R DLBCL.

Background China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) and introduced 1 dose of inactivated poliovirus vaccine on 1 May 2016. We assessed the impact of the switch on the immunity level against poliovirus, especially type 2. Methods Children born between 2014 and 2017, who were brought to the hospitals in Urumqi city, Xinjiang Province in 2017, were enrolled and blood samples were collected to test for antibody titers against poliovirus. A comparison of seroprevalence between the children born before (preswitch group) and after the switch (postswitch group) was performed to assess the impact of the switch on the immunity level against polio. Results A total of 172 subjects were enrolled. The overall seroprevalences were 98.8%, 79.1%, and 98.3% for types 1, 2, and 3, respectively. Seroprevalence for type 2 significantly decreased from 91.6% in the preswitch group to 67.4% in the postswitch group, but no statistically significant change was observed for both types 1 and 3. Conclusions The switch from tOPV to bOPV can provide high-level immunity against types 1 and 3 but not against type 2, indicating a high risk of type 2 vaccine-derived poliovirus emergence and transmission.

Multiple myeloma (MM) is an immunoglobulin-producing tumor of plasma cells, which occurs commonly in the elderly. The incidence of myocardial amyloidosis with MM is extremely low and early clinical manifestations are nonspecific. The diversity of clinical manifestations and first episode symptoms often cause misdiagnosis in young patients with myocardial amyloidosis following MM. In this study, we analyzed the clinical data of a young woman with MM and impaired cardiac function combined with echocardiography, electrocardiography (ECG), laboratory data, cell Congo Red staining, and other manifestations to diagnose amyloidosis. Considering the rapid progression, short survival, and poor prognosis in most patients, a clear, definitive, and timely diagnosis is essential for the treatment of patients with MM complicated with myocardial amyloidosis.

Objective: To assess how acupuncture and related techniques affect weight-related indicators and cardiovascular risk factors compared with non-acupuncture interventions in overweight and obese patients. Methods: We searched PubMed, Embase and CENTRAL up to 19 April 2018 and included relevant randomised controlled trials (RCTs). Weighted mean differences (WMDs) and 95% confidence intervals (CI) were pooled using the inverse variance method with random-effects model. Prespecified hypotheses were tested in meta-regression to investigate the source of heterogeneity. Statistical software packages used were RevMan 5.3.5 and Stata 14.0. Results: Thirty-three RCTs were included (n=2503 patients). Compared with non-acupuncture interventions, acupuncture produced a greater reduction in body weight (WMD −1.76 kg, 95% CI −2.22 to −1.30, I2=77%; moderate quality), body mass index (WMD −1.13 kg/m2, 95% CI −1.38 to −0.88, I2=85%; low quality) and waist circumference (WMD −2.42 cm, 95% CI −3.22 to −1.62, I2=75%; moderate quality). Acupuncture plus lifestyle intervention resulted in a greater reduction in body weight than acupuncture alone (MD −1.94 kg, 95% CI −3.17 to −0.70). Acupuncture also led to a greater reduction in total cholesterol (WMD −12.87 mg/dL, 95% CI −22.17 to −3.57, I2=87%; very low quality) and low-density lipoprotein cholesterol (WMD −13.52 mg/dL, 95% CI −21.47 to −5.58, I2=74%; low quality). The differences were not statistically significant for blood glucose or blood pressure. Conclusion: In the short term, acupuncture and related techniques may produce a small but statistically significant degree of weight loss based on moderate- to low-quality evidence, and improve serum lipid parameters based on low- to very-low-quality evidence. Their effects on blood glucose and blood pressure remain uncertain.

Memory is no longer a privilege of adaptive immunity. Innate immune cells can exhibit a long-term immune activation after infection or vaccination, which is called "trained immunity." In addition to defense against mycobacterial infection, BCG-induced trained immunity can also exert nonspecific protection, which is regulated by metabolic rewiring and epigenetic reprograming. Enhanced glycolysis and glutamine-driven tricarboxylic acid cycle have been proven to be important metabolic pathways for trained immunity induced by BCG, which is dependent on Akt/mTOR pathway.

EV-A120 is a recently identified serotype of the enterovirus A species. Only one full-length genomic sequence is currently available in GenBank, and very few studies have been conducted on EV-A120 globally. Thus, additional information and research on EV-A120 are needed to explore its genetic characteristics, phylogeny, and relationship with enteroviral disease. In this study, we report the phylogenetic characteristics of a EV-A120 strain (Q0082/XZ/CHN/2000) from Tibet, China. The amino acid sequence similarity and nucleotide sequence similarity of the full-length genomic sequence of this EV-A120 strain and the EV-A120 prototype strain were 96.3% and 79.9%, respectively, showing an evolutionary trend. Recombination analysis found intraspecies recombination in the 5′ -UTR, 2B, 2C, and 3D regions. Serum neutralization testing of the EV-A120 (Q0082) strain was also carried out. Low serum-positive rates and geometric mean titres (GMTs) indicated that the extent of EV-A120 transmission and exposure in the population was very limited compared with that in the outbreaks of EV-A71 and CV-A16 in China since 2008. The EV-A120 strain (Q0082) is non-temperature sensitive, indicating its potential to spread in the population. In summary, this study reports the full-length genomic sequence of EV-A120 and provides important information for its global molecular epidemiology.

Objective: This study combines quantitative research of personality traits with demographic data to analyze the influencing factors of the mental health of freshmen in colleges and universities, and provides a reference to/from future college freshmen’s mental health education and management. Methods: A census method was used to survey freshmen admitted to the Yangtze University, including general demographic characteristics, a 16-person cartel questionnaire (16-PF), and a 90-item self-assessment scale (SCL-90). Results: The mental health status of freshmen in colleges and universities was good, with 16.2% (1488 persons) being tested positive. Among the positive screened samples, obsessive-compulsive symptom factor, interpersonal relationship sensitivity factor, anxiety factor, depression factor, and increased scores were the main characteristics. The results of binary classification logistic regression analysis showed that humanities and social sciences, non-urban household registration, and non-sturdy families, undergraduate and college students are at higher risk of being screened for SCL-90. Conclusion: Freshmen in colleges and universities are generally in good mental health. Under the interaction of biological, psychological, and social factors, some freshmen are more prone to neurological symptoms such as depression, anxiety, and obsessive-compulsive symptoms. At the same time, they are also more likely to be troubled by interpersonal relationships. The appearance of neurological symptoms and the classification of people that are troubled by interpersonal relationships are also special. According to the conclusions of this study, the emphasis is on accurately identifying the symptoms of neonatal neurosis in colleges and universities, and early intervention, and managing high-risk groups that may have the above symptoms, and reducing the prevalence of psychological and mental disorders in college freshmen.

What is already known about this topic? After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. What is added by this report? Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. What are the implications for public health practices? Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

Cladribine is a purine nucleoside analog used to treat B-cell chronic lymphocytic leukemia and hairy cell leukemia, also functions as an inhibitor of DNA synthesis to block the repair of the damaged DNA. The therapeutic role of cladribine against diffuse large B-cell lymphoma cells (DLBCL) is still undefined. In the present study, we demonstrated that cladribine inhibited cell proliferation and induced G1 phase arrest in human DLBCL cells. Furthermore, we showed that cladribine induced apoptosis by decreasing the expression of c-FLIPL and increasing the expression of DR4 and the cleaved form of caspase8. Cladribine also upregulated the expression of Bax, and downregulated the expression of Mcl-1 and Bcl-2 in a dose-dependent manner. It also activated endoplasmic reticulum (ER) stress, and ATF4 expression was required for cladribine induced apoptosis. Also, we showed that suberoylanilide hydroxamic acid (SAHA) enhanced the pro-apoptotic role of cladribine. Collectively, cladribine activated extrinsic and intrinsic apoptotic signaling pathways via stimulating ER stress signaling pathway and eliciting synergistic effect with SAHA in DLBCL cells.

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-reactive immunities.

Background. 5-Fluorouracil (5-FU) has been widely applied in treating cancers. However, its usage is largely limited in hepatocellular carcinoma (HCC), due to acquired resistance. Here, we aim to identify target proteins and investigate their roles in 5-FU sensitivity of HCC cells. Methods. Mass spectrometry (MS) proteomics was performed on 5-FU-resistant cell line (BEL7402/5-FU) and its parental cell line (BEL7402) with 5-FU treatment. In order to identify potential targets, we compared the proteomics between two cell line groups and used bioinformatics tools to select hub proteins from all differentially expressed proteins. Results. We finally focused on a group of cell cycle-related kinases (CDKs). By CCK8 assay, we confirmed that the CDK inhibitor significantly decreased the IC50 of 5-FU-resistant cells. Conclusions. Our study verified that CDK inhibition can reverse 5-FU resistance of HCC cells.

The C4 sub-genotype of Enterovirus 71(EV71) is identified as the most dominant sub-genotype circulating in Chinese mainland since 1998, while the circulation situation of EV71 before 1998 is not well established due to insufficient experimental data. The C1 sub-genotype of EV71 has not been reported in Chinese mainland by now. Based on AFP surveillance system of the mainland of China, this study performed a retrospective study of AFP cases for 1985-1999༚A strain of EV-A71 C1 sub-genotype was found. To our knowledge, this strain (SD92-41) is the first C1 sub-genotype reported in Chinese mainland. This study proves that the C1 gene subtype also appeared in Chinese mainland, but it is not clear whether it is an imported or a local epidemic strain. With sufficient information from retrospective studies, the source of the SD92-41 strain will be identified, and the prevalence of EV-A71 in Chinese mainland before 1998 will be clearer.

A variety of indolent lymphomas, particularly marginal zone lymphoma (MZL) and follicular lymphoma (FL) can be histologically transformed to diffuse large B-cell lymphoma (DLBCL). Little is known about the disparity of clinicopathologic characteristics between transformed DLBCL (tDLBCL) and primary DLBCL (pDLBCL).This retrospective study analyzed the clinicopathological hallmarks of 10 tDLBCL (7 MZL and 3 FL) and 40 pDLBCL from the Affiliated Hospital of Xuzhou Medical University.Patients of tDLBCL had a higher ECOG score, more B-symptoms, and lower serum albumin level than those in pDLBCL (60.0% vs. 7.50%, 40.0% vs. 10.0%, and 90.0% vs. 10.0%, respectively, p0.01). Pathologically, tDLBCL had more c-Myc and BCL-2 dual-expression than that in pDLBCL (60.0% vs. 25.0%, p0.01). The positive rate of CD5 expression and the proportion of high Ki-67 score in tDLBCL were higher than those in pDLBCL (50.0% vs. 7.5%, 50.0% vs. 32.5%, respectively, p0.01). The median overall survival and progression-free survival were 14 months and 11 months in tDLBCL, 35 months and 28 months in pDLBCL (p0.05 and p0.001).Our results demonstrate that tDLBCL manifested aggressive clinical course and pathological features of Myc/BCL-2 expression, CD5 expression, and high Ki-67 score.

A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis (AFP) in children so that potential wild polioviruses and vaccine-derived poliovirus (VDPV) could be identified on time. Two outbreaks associated with type I circulating VDPVs, eight native independent type I ambiguous VDPVs (aVDPV), and one imported aVDPV were identified during the AFP case surveillance in China from 1995 to 2019. The VP1 coding region of the Chinese type I VDPVs differed from the polio vaccine strain by 1.00%–3.75% (9–34 substitutions in 906 nucleotides). Most of the Chinese type I VDPV strains shared 4 amino acid substitutions in the neutralizing antigenic (NAg) sites: 3 located at the BC loop, which formed the NAg site 1, and another at NAg site 3a. All of the Chinese type I VDPVs identified during the AFP case surveillance were young VDPVs, which indicated a limited viral replication resulted from the administration of the initiating oral polio vaccine (OPV) dose. VDPVs can emerge and spread in isolated communities with immunity gaps and the circulation ceases following a mass immunization with OPV. As such, high-quality surveillance permitted very early detection and response and it played a key role in stalling the widespread circulation of the emergent cVDPV strains in China.

The C4 sub-genotype of Enterovirus 71 (EV71) has been identified as the most dominant sub-genotype circulating in the Chinese mainland since 1998. The circulation situation of EV71 before 1998 is not well established due to insufficient experimental data. The C1 subgenotype of EV71 has not yet been reported in the Chinese mainland by now. Based on the AFP surveillance system of the mainland of China, this study conducted a retrospective study of AFP cases for 1985–1999: a strain of EV-A71 C1 subgenotype was found. To our knowledge, this strain (SD92-41) is the first C1 sub-genotype reported in the Chinese mainland. This study demonstrates that the C1 gene subtype also appeared in the Chinese mainland, but it is unknown whether it is an imported or a local epidemic strain. With sufficient information known from retrospective studies, the source of the SD92-41 strain will be identified and the prevalence of EV-A71 in the Chinese mainland before 1998 will be clearer.

Background: To assess the influence of ocular residual astigmatism to anterior corneal astigmatism in children with low and moderate myopia.Methods: Refractive astigmatism was obtained by subjective manifest refraction. Anterior corneal astigmatism was obtained by IOL Master. Using Thibos vector analysis to calculate ocular residual astigmatism. Correlation analysis was used to assess the relationship between the magnitude of ocular residual astigmatism and anterior corneal astigmatism. The influence of ocular residual astigmatism to anterior corneal astigmatism was evaluated by Physical method.Results: The study analyzed 241 right eyes of 241 children aged 8 to 18 years old. In this study, the median magnitude of ocular residual astigmatism was 1.02 D, with interquartile range was 0.58 D. Against-the-rule ocular residual astigmatism was seen in 232 eyes (96.3%). There was a significant and moderate correlation between ocular residual astigmatism and anterior corneal astigmatism (r = 0.50, P < 0.001). The ocular residual astigmatism in 240 eyes (99.6%) had a compensatory effects on anterior corneal astigmatism. The mean compensation value was 1.00 ± 0.41 D (rang 0.02 D to 2.34 D). Based on this effect, 37 eyes had different axial classification of anterior corneal astigmatism and refractive astigmatism. By contrast, one eye (0.4%) had oblique ocular residual astigmatism and superimposed with-the-rule anterior corneal astigmatism.Conclusions: The magnitude of ocular residual astigmatism was relatively huge in myopia children and predominantly compensated anterior corneal astigmatism. The ocular residual astigmatism should be assessed first before fitting orthokeratology.