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Tianrui Zhang,1,* Sha Fu,1,* Xiaofeng Cao,2 Yangjingyi Xia,1 Manyan Hu,1 Qinghua Feng,1 Yujun Cong,1 Yuan Zhu,1 Xiaogang Tang,1 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Neurology, Jiangyan Hospital of Chinese Medicine, Taizhou, Jiangsu, 225500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minghua Wu; Xiaogang Tang, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Tel +8613951786719, Email yfy0069@njucm.edu.cn; zhongyiTXG@163.comPurpose: According to many previous studies, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and hypersensitive C-reactive protein (CRP) are commonly used as important indicators to assess the prognosis of intravenous thrombolysis in AIS patients. Based on this, we used two novel biomarkers C-NLR (CRP/neutrophil-to-lymphocyte ratio) and C-LMR (CRP×lymphocyte-to-monocyte ratio) to investigate their correlation with 90-day outcomes in AIS patients after intravenous thrombolysis.Patients and Methods: A total of 204 AIS patients who received intravenous thrombolysis at the Stroke Center of Jiangsu Province Hospital of Chinese Medicine from January 2021 to December 2022 were retrospectively included. All patients were followed up 90 days after thrombolysis to assess their prognosis. Patients with a modified Rankin scale score (mRS) of 3– 6 were included in the unfavorable outcome group, and those with a score of 0– 2 were included in the favorable outcome group. Logistic regression analysis, receiver operating characteristic (ROC) curve, and Kaplan–Meier survival curve were used to investigate the association between C-NLR, C-LMR, and 90-day prognosis in AIS patients treated with early intravenous thrombolysis.Results: C-NLR (OR=1.586, 95% CI=1.098~2.291, P=0.014) and C-LMR (OR=1.099, 95% CI=1.025~1.179, P=0.008) were independent risk factors for 90-day prognosis of AIS patients treated with early intravenous thrombolysis. The higher C-NLR and C-LMR were associated with unfavorable prognosis.Conclusion: C-NLR and C-LMR can be used as biomarkers to predict prognosis of AIS patients treated with early intravenous thrombolysis.Keywords: modified rankin scale, reperfusion therapy, inflammatory reaction, cerebral vascular disease, clinical prognosis

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate (Macaca leonina). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice (Mus musculus var. albino) and rats (Rattus norvegicus). These preclinical results indicate that Nanocovax is safe and effective.

Remobilization is an important mechanism of resource conservation in plants. However, our understanding of whether the responses of resource remobilization to global warming differ between deciduous and evergreen trees remains unclear. We assessed resource remobilization from leaves to 1-year-old shoots in a deciduous (Betula ermanii) and an evergreen (Quercus aquifolioides) species along elevational gradients (i.e., temperature gradient) at the end of growing season. We aimed to test the hypotheses that the reallocation rate increased with increasing elevation and that more resources were reallocated from leaves to storage tissues in deciduous species than in evergreen species. We analyzed the concentrations of non-structural carbohydrates (NSC), nitrogen (N) and phosphorus (P), and compared the differences in remobilization efficiency of NSC, N, and P between leaves and shoots within each species and between the two species along the elevational gradients. Due to the different strategies of evergreen and deciduous species in nutrients use, the deciduous species had higher N and P remobilization rate, but lower remobilization rate of sugars, starch, and NSC than the evergreen species at the end of growing season. The remobilization rate of NSC, N, and P was significantly higher in trees at their upper limits compared to lower elevations. Our results suggest that trees reallocate resources from leaves to storage tissues before leaf senescence or at the end of growing season, to increase the resource use efficiency and to adapt to the harsh alpine environments. These results contribute to better understanding of the alpine treeline phenomenon in a changing world.

Chao Liu,1,2 Bing Sun,2 Bin Xu,1 Xiangying Meng,2 Lan Li,1 Yang Cong,2 Jiannan Liu,2 Qian Wang,2 Liang Xuan,2 Qibin Song,1 Shikai Wu2 1Cancer Center, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People’s Republic of China Introduction: Programmed cell death protein 1 (PD-1), an immune checkpoint molecule, has recently been recognized as a predictive and prognostic biomarker in several malignant tumors, but its diagnostic value remains largely unknown. We aimed to investigate the differential diagnostic efficiency of PD-1 and other immune molecules and propose a panel of immune molecules combined with cancer antigen 15-3 (CA15-3) to distinguish breast cancer (BC) from benign breast disease (BBD).Patients and methods: Ninety-one eligible BC patients and 31 BBD patients were enrolled. Pretreatment peripheral blood was collected and tested for mRNA expression of PD-1, cytotoxic T lymphocyte antigen 4, forkhead box P3, transforming growth factor beta, interleukin-10 (IL-10), IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 by quantitative reverse transcription PCR.Results: The diagnostic areas under curve (AUCs) of PD-1, IL-2Rα, and IL-10 for BC–BBD discrimination were 0.764, 0.758, and 0.743, respectively. The diagnostic efficiencies of these three parameters in distinguishing early-stage or advanced BC from BBD were consistent with a role in BC–BBD discrimination. A panel of PD-1 + IL-10 + IL-2Rα + CA15-3 showed the highest AUC (0.862), with a sensitivity of 0.933 and a specificity of 0.724, for BC–BBD discrimination. In addition, for early-stage BC discrimination, this panel also had the highest AUC (0.811), with a sensitivity of 0.933 and a specificity of 0.614, while for advanced BC discrimination, a panel of PD-1 + IL-10 + CA15-3 exhibited the highest AUC (0.896), with a sensitivity of 0.933 and a specificity of 0.783.Conclusion: These data indicate that the panel containing PD-1, IL-2Rα, IL-10, and CA15-3 can effectively discriminate BC from BBD with a high efficiency. After further confirmation, it could be used to complement conventional imaging modalities, especially in discriminating early-stage BC from BBD. Keywords: breast cancer, immune checkpoint, PD-1, CTLA-4, IL-2Rα, diagnosis, biomarker

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

Abstract Background Quality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region. Methods A retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed. Results The overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a “two-peak” pattern, the peaks of which were observed in the

Abstract The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0–2 years (18.09%, 1054/5,828) and lowest among adults aged 45–64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time.

Abstract Background SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB.

Background Knowledge sharing of family doctor teams under the county medical community is an important way of interaction between the county and rural institutions, which plays an important role in enhancing the quality of regional medical and health services and improving the health of residents. Objective To investigate the knowledge sharing among family doctor teams under the county medical community, to explore its influencing factors, and to provide a scientific basis for promoting knowledge management and capacity enhancement within family doctor teams. Methods From October to December 2022, multistage sampling was used for selecting 381 family doctor teams under two county medical communities were selected as study subjects in Hubei Province using the convenience sampling method, and a self-administered team knowledge-sharing questionnaire was used to investigate the knowledge-sharing level of the included subjects, and multivariate linear stepwise regression analyses were used to explore the influencing factors of the knowledge-sharing of family doctor teams, including two dimensions of explicit knowledge sharing and implicit knowledge sharing. Results The total knowledge sharing score of family doctor teams under county medical communities was (27.84±3.84), and the mean item level scores of the two dimensions of explicit and implicit knowledge sharing were (5.51±0.79) and (5.61±0.77), respectively; the results of the multivariate linear stepwise regression analysis showed that the heterogeneity of academic qualifications, intensity of team communication, intensity of team activities, motivation of members to learn, the use of platform carriers, and the team leader's role were the influencing factors of knowledge sharing of family doctor teams under the county medical community (P

Background The effectiveness of family physician teams under the county medical community is low, and the current status of team management is not yet clear, the perceived status of team management for members with different characteristics is not yet clear. Objective To understand the current situation of family doctor team management under the county medical community, and to provide a basis for further refinement and improvement of family doctor team management. Methods From October to December 2022, a total of 1 724 key members of 429 family doctor teams under the county medical communities in Hubei Province were surveyed using a self-developed questionnaire, which included the management of team configurations, the management of team interactions and the results of team management. Differences in perceptions of team management between family doctor team members with different characteristics were analysed using chi-squared test and ANOVA, and Pearson correlation was used to analysis the correlation between team interaction management and team management outcome factors. Results Among 1 724 survey respondents, 62.9% (1 084/1 724) perceived that team assessment and incentive measures were effective, and 88.7% (1 530/1 724) perceived that they had a reasonable allocation of family doctor team personnel. The respondents had a score of (22.3±5.3) for the intensity of internal team interactions and a score of (22.0±5.3) for the perceived intensity of the team's interaction and liaison with the outside. Regarding family doctor team members' perception of team management results, team members' perceived team goal achievement, i.e., team task performance, scored (33.1±7.4), perceived satisfaction with the team scored (22.3±4.9), and perceived team's ability and potential for future development scored (27.9±6.3), while the total scores of the three dimensions were 0-36, 0-24, 0-30. Comparison of team configuration management, team interaction management, and perceptions of team management outcomes between family doctor team members of different positions, titles, and ages showed statistically significant differences (P

Abstract Background & aims Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. Methods Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. Results PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. Conclusion The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.