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Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950−2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus , Dermacentor nutalli and Rhipicephalus microplus . Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance. Ticks are an important vector of disease in China, posing threats to humans, livestock and wild animals. Here, Zhao et al. compile a database of the distributions of the 124 tick species known in China and 103 tick-borne pathogens and predict the additional suitable habitats for the predominant vector species.

Background COVID-19 patients with long incubation period were reported in clinical practice and tracing of close contacts, but their epidemiological or clinical features remained vague. Methods We analyzed 11,425 COVID-19 cases reported between January–August, 2020 in China. The accelerated failure time model, Logistic and modified Poisson regression models were used to investigate the determinants of prolonged incubation period, as well as their association with clinical severity and transmissibility, respectively. Result Among local cases, 268 (10.2%) had a prolonged incubation period of > 14 days, which was more frequently seen among elderly patients, those residing in South China, with disease onset after Level I response measures administration, or being exposed in public places. Patients with prolonged incubation period had lower risk of severe illness (OR adjusted  = 0.386, 95% CI: 0.203–0.677). A reduced transmissibility was observed for the primary patients with prolonged incubation period (50.4, 95% CI: 32.3–78.6%) than those with an incubation period of ≤14 days. Conclusions The study provides evidence supporting a prolonged incubation period that exceeded 2 weeks in over 10% for COVID-19. Longer monitoring periods than 14 days for quarantine or persons potentially exposed to SARS-CoV-2 should be justified in extreme cases, especially for those elderly.

Scrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear. Clinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients. A total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%-16.1%) and 10.3% (95% CI 9.0%-11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96-152.67, p<0.001) and 13.22 (1.54-113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33-18.64, p<0.001) and 3.17 (1.97-5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001). The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.

Anlotinib demonstrated encouraging therapeutic activity as third-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Programmed cell death protein 1 (PD-1) inhibitors also exhibited promising and durable response against previously-treated advanced NSCLC. Therefore, the present study aimed to determine the feasibility and safety of anlotinib plus PD-1 inhibitors for previously-treated NSCLC in clinical practice. This retrospective study included 56 patients with advanced NSCLC treated with systemic treatment previously. Patients included were treated with anlotinib plus PD-1 inhibitors in clinical practice. Therapeutic outcomes of the patients were evaluated radiologically using target lesions, and the prognostic outcomes were generated by follow-up. Adverse reactions experienced throughout the treatment were documented and analyzed. Between August 2018 and November 2022, 56 patients with advanced NSCLC were eligible to participate in this study consecutively. Therapeutic outcomes resulted in an overall response rate of 28.6% [95% confidence interval (CI): 17.3%-42.2%] and a disease control rate of 91.1% (95% CI: 80.4%-97.0%). Furthermore, this combination regimen among the 56 patients yielded a median progression-free survival (PFS) of 6.5 months (95% CI: 4.81-8.19) and a median overall survival (OS) of 15.8 months (95% CI: 10.23-21.37), respectively. And the median duration of response (DoR) among patients who responded was 8.3 months (95% CI: 4.38-12.22). Additionally, adverse reactions of all grades throughout the treatment were observed in 50 patients (89.3%), and adverse reactions of grade ≥3 were detected in 23 patients (41.1%). Fatigue, hypertension, diarrhea, nausea, and vomiting were the most common adverse reactions. Association analysis between PFS and baseline characteristic subgroups indicated that ECOG score and number of metastatic lesions might be potential predictors of PFS in the exploratory analysis. Anlotinib plus PD-1 inhibitors demonstrated a tolerable safety profile and encouraging therapeutic activity as subsequent-line therapy in patients with advanced NSCLC. This conclusion should be confirmed in prospective large-scale clinical trials subsequently.

Abstract Background The frequent movement of population between countries brings an increasing number of travel-related infections. This study aims to define the spectrum and dynamics of imported infections observed from international travel in the Chinese mainland. Methods Sick travellers were screened by inbound sentinel surveillance and post-travel clinic visits from 2014 to 18. The infections were classified as respiratory, gastrointestinal, vector-borne, blood/sexually transmitted and mucocutaneous. The analysed variables included the place of origin of the travellers (Chinese or foreign) and the time when travel-related infection was present (at the time of return, during travel and post-travel visits to the clinic). Results In total, 58 677 cases were identified amongst 1 409 265 253 travellers, with an incidence of 41.64/million, comprising during-travel incidence of 27.44/million and a post-travel incidence of 14.20/million. Respiratory infections constituted the highest proportion of illnesses during travel (81.19%, 31 393 of 38 667), which mainly came from Asian countries and tourists; with influenza virus and rhinovirus infections being mainly diagnosed. Vector-borne diseases constituted the highest proportion of post-travel illnesses (98.14%, 19 638 of 20 010), which were mainly diagnosed from African countries and labourers; with malaria and dengue fever being mainly diagnosed. The differential infection spectrum varied in terms of the traveller’s demography, travel destination and travel purpose. As such, a higher proportion of foreign travellers had blood/sexually transmitted diseases (89.85%, 2832 of 3152), while Chinese citizens had a higher prevalence of vector-borne diseases (85.98%, 19 247 of 22 387) and gastrointestinal diseases (79.36%, 1115 of 1405). The highest incidence rate was observed amongst travellers arriving from Africa, while the lowest was observed amongst travellers arriving from Europe. Conclusions The findings might help in preparing recommendations for travellers and also aid in primary care or other clinics that prepare travellers before trips abroad. The findings will also help to identify locations and the associated types of infections that might require attention.

Background：Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit （NICU） of China.Methods：All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results：A total of 744 newborns died during the l-year survey,accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3% of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases （56.5%） occupied the largest proportion ofpreterm deaths while infection （27%） and neurologic diseases （22%） were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents＇ concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions：Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

BACKGROUND:In the management of critically ill patients,the assessment of volume responsiveness and the decision to administer a fluid bolus constitute a common dilemma for physicians.Static indices of cardiac preload are poor predictors of volume responsiveness.Passive leg raising(PLR) mimics an endogenous volume expansion(VE) that can be used to predict fluid responsiveness.This study was to assess the changes in stroke volume index(SVI) induced by PLR as an indicator of fluid responsiveness in mechanically ventilated patients with severe sepsis.METHODS:This was a prospective study.Thirty-two mechanically ventilated patients with severe sepsis were admitted for VE in ICU of the First Affiliated Hospital,Zhejiang University School of Medicine and Ningbo Medical Treatment Center Lihuili Hospital from May 2010 to December 2011.Patients with non-sinus rhythm or arrhythmia,parturients,and amputation of the lower limbs were excluded.Measurements of SVI were obtained in a semi-recumbent position(baseline) and during PLR by the technique of pulse indicator continuous cardiac output(PiCCO) system prior to VE.Measurements were repeated after VE(500 mL 6%hydroxyethyl starch infusion within 30 minutes)to classify patients as either volume responders or non-responders based on their changes in stroke volume index(ASVI) over 15%.Heart rate(HR),systolic artery blood pressure(ABPs),diastolic artery blood pressure(ABPd),mean arterial blood pressure(ABPm),mean central venous pressure(CVPm)and cardiac index(CI) were compared between the two groups.The changes of ABPs,ABPm,CVPm,and SVI after PLR and VE were compared with the indices at the baseline.The ROC curve was drawn to evaluate the value of ASVI and the change of CVPm(ACVPm) in predicting volume responsiveness.SPSS 17.0 software was used for statistical analysis.RESULTS:Among the 32 patients,22 were responders and 10 were non-responders.After PLR among the responders,some hemodynamic variables(including ABPs,ABPd,ABPm and CVPm)were significantly elevated(101.2±17.6 vs.118.6±23.7,P=0.03;52.8±10.7 vs.64.8±10.7,P=0.006;68.3+11.7 vs.81.9±14.4,P=0.008;6.8±3.2 vs.11.9±4.0,P=0.001).After PLR,the area under curve(AUC) and the ROC curve of △SV1 and ACVPm for predicting the responsiveness after VE were0.882±0.061(95%CI 0.759-1.000) and 0.805±0.079(95%CI 0.650-0.959) when the cut-off levels of ASVI and ACVPm were 8.8%and 12.7%,the sensitivities were 72.7%and 72.7%,and the specificities were 80%and 80%.CONCLUSION:Changes in ASVI and ACVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.

目的：报道高迁移率族蛋白N2（HMGN2）对大肠埃希菌（Escherichia coli）K12的抗菌功能,并对其抗菌机制进行探讨,同时检验HMGN2对中性粒细胞是否具有趋化活性。创新点：从分子水平上探讨了HMGN2对大肠埃希菌的抗菌机制。方法：用反相高效液相色谱法从人类子宫纤维囊腺瘤中提取组织细胞的HMGN2分子（tH MGN2）。诱导重组表达质粒PET-32a-c（＋）-HMGN2表达重组蛋白HMGN2（rH MGN2）。用琼脂糖凝胶弥散法对HMGN2的抗菌活性进行检测,并用微量肉汤稀释法测定HMGN2的最小抑菌浓度（MIC）。通过膜通透性实验和凝胶阻滞实验检测HMGN2对细菌菌膜和核酸的作用。通过结晶紫实验和电镜扫描验证HMGN2的抗生物被膜形成作用。通过氮蓝四唑（NBT）法和Transwell趋化法分别验证HMGN2的活化效应和对中性粒细胞的趋化活性。结果：我们分离纯化获得了高质量的天然和重组HMGN2分子,同时验证了HMGN2对革兰氏阴性大肠埃希菌具有较强的抗菌活性,MIC为16.25μg/ml。细菌膜通透性实验发现HMGN2使大肠埃希菌膜渗透性明显增大。HMGN2分子与大肠埃希菌K12染色体DNA和质粒DNA的结合均呈浓度依赖效应。银染和扫描电镜结果显示,HMGN2与大肠埃希菌共培养可干扰细菌生物被膜形成,并破坏已形成的早期和成熟生物被膜。然而HMGN2对中性粒细胞没有活化作用和趋化作用。结论：作为抗菌肽,HMGN2对大肠埃希菌有良好的抗菌活性。该活性可能通过影响细胞膜的通透性和干扰细菌DNA转录以及干扰生物被膜而发挥作用。

Anxiety and depression are great public health concerns among college students. The purpose of this study was to explore whether sleep quality and quality of life (QoL) play mediating roles in anxiety and depression among Chinese college students. A total of 2757 college students (mean age = 19.07; SD = 1.14) completed the questionnaires, including a brief demographic survey. The 2-item General Anxiety Disorder (GAD-2) and the 2-item Patient Health Questionnaire (PHQ-2) were used to assess the symptoms of anxiety and depression, respectively. And the Pittsburgh Sleep Quality Index (PSQI) and the Short-Form 36 Health Survey (SF-36) were used to evaluate college students' sleep quality and QoL, respectively. Mediation analyses were conducted by using PROCESS macro in the SPSS software. Anxiety had both direct and indirect effects on depression. Sleep quality and QoL were not only independent mediators in the relationship between anxiety and depression but also chain mediators. The results of the current study highlight the crucial role of early intervention for depression with a focus on college students with anxiety, more especially, on those with poorer sleep quality and lower QoL.

Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18–65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA, excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12–16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4–90·6]) than in the standard therapy group (75·7% [69·9–81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. For the Chinese translation of the abstract see Supplementary Materials section.