Zhimin Tao

Natural killer (NK) cells are potent immune modulators that can quickly lyse tumor cells without prior sensitization or recognition of specific tumor antigens. However, NK cells in the tumor microenvironment are frequently dysfunctional. Despite advances in cytokine therapy and NK cell adoptive transfer, tumor-expressed ligands that interact with NK cell-expressed checkpoint receptors can greatly suppress NK cell-mediated tumor lysis, leading to suboptimal therapeutic outcomes. Here we explored a new approach of utilizing cellular nanovesicles (NVs) as artificial controllers of cellular immunity to redirect and activate NK cells for tumor eradication. Through this strategy, we engineered HEK293 cell-derived NVs genetically modified to display two distinct types of surface monoclonal antibodies (mAbs), namely human cluster of differentiation 16 (CD16) and human epidermal growth factor receptor 2 (HER2) antibodies, generating dual aCD16/aHER2 NVs that simultaneously target CD16-expressing NK cells and HER2-expressing gastric cancer cells. Following thorough characterization, the aCD16/aHER2 NVs exhibited highly potent and specific anti-tumor activity both in vitro and in vivo. This preclinical work demonstrates the feasibility of using dual-targeting NVs to navigate functional NK cells to recognize and eliminate gastric cancers, presenting aCD16/aHER2 NVs as an effective and versatile platform for cancer immunotherapy.

Background: Malnutrition is common in patients with sepsis and is associated with prolonged hospitalization and increased mortality. Early assessment of nutritional status using standardized nutritional assessment tools may be important for risk stratification and outcome prediction. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library from database inception to November 2025. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment, with disagreements resolved through discussion. Cohort and case-control studies evaluating nutritional assessment tools in patients with sepsis and reporting mortality-related outcomes were included. Results: A total of 11 studies involving 34,810 patients were included. All included studies had a Newcastle-Ottawa Scale (NOS) score of ≥7. Seven nutritional assessment tools were evaluated: the Prognostic Nutritional Index (PNI), Nutrition Risk in the Critically Ill (NUTRIC) score, modified NUTRIC (mNUTRIC) score, Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), Nutritional Risk Screening 2002 (NRS 2002), and blood urea nitrogen-to-albumin ratio (BAR). Quantitative synthesis was feasible only for PNI and GNRI because of the limited number and heterogeneity of studies evaluating the other tools. A random-effects meta-analysis of studies evaluating PNI showed a pooled hazard ratio (HR) of 0.57 (95% CI: 0.51–0.64), indicating that higher PNI scores were associated with lower short-term mortality in patients with sepsis. The remaining tools were therefore summarized narratively. Conclusions: Among the nutritional assessment tools included, the NUTRIC score appeared to have favorable predictive performance and may be one of the more promising tools based on currently available evidence. Early nutritional assessment may help identify patients at increased risk of poor outcomes and support clinical risk stratification. However, the evidence remains limited because most studies were retrospective and single-center, and direct quantitative comparisons among all nutritional assessment tools were not possible. The included observational studies do not demonstrate that use of these tools or subsequent nutritional interventions improves patient outcomes. Further prospective, multicenter studies are required to validate their prognostic utility in sepsis research.

This review summarizes the design, oxygen-delivery mechanisms, and translational challenges of artificial blood substitutes, including perfluorocarbons, hemoglobin-based carriers, and emerging oxygen nanocarriers.

Background: Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, is an emerging tick-borne infectious disease associated with substantial case fatality and poses a considerable public health burden. Interleukin-10 (IL-10), an important anti-inflammatory and immunoregulatory cytokine, may reflect the magnitude of immune dysregulation in SFTS. This systematic review and meta-analysis primarily aimed to evaluate the association between serum IL-10 levels and mortality in patients with SFTSV infection. As a secondary exploratory objective, we assessed the threshold-based prognostic accuracy of IL-10 for fatal outcomes when sufficient data were available. Methods: PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and CQVIP were searched from database inception to October 11, 2025. Prospective and retrospective cohort studies, and case-control studies reporting serum IL-10 levels in survivors and non-survivors with laboratory-confirmed SFTSV infection were eligible. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale (NOS) and risk of bias using the Quality In Prognosis Studies (QUIPS) tool for studies on prognostic factors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool for studies contributing threshold-based prognostic accuracy data. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a prespecified random-effects model. Sensitivity analyses, subgroup analyses, meta-regression, funnel plots, and Egger’s test were used to evaluate the robustness of the findings and possible small-study effects. Results: Twelve studies involving 1,270 patients with SFTSV infection were included, comprising 290 non-survivors and 980 survivors. Serum IL-10 levels were significantly higher in non-survivors than in survivors (pooled SMD = 2.08, 95% CI: 1.40-2.76; PI ² = 94%, Ppost hoc , non-validated cut-off values and therefore remained exploratory. The certainty of evidence for the association between IL-10 levels and mortality was rated as very low because of residual confounding, inconsistency, indirectness, and possible small-study effects. Conclusion: Elevated serum IL-10 levels were associated with mortality in SFTS; however, the certainty of evidence was very low. IL-10 should therefore be considered a candidate prognostic biomarker requiring further prospective validation rather than a clinically established stand-alone prognostic tool. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD420251149587.

Background: Human adenovirus (HAdV) is an important cause of respiratory and systemic infection in children. Since the COVID-19 pandemic, changes in population immunity, transmission patterns, and circulation of respiratory pathogens may have altered the epidemiological and clinical profile of pediatric HAdV infection. However, data comparing pediatric HAdV infection before and after the COVID-19 pandemic remain limited. Methods: We analyzed pediatric patients with HAdV infection admitted to four tertiary hospitals in Jiangsu Province, China, before and after the COVID-19 pandemic. Epidemiological features, including seasonal distribution and age patterns, were compared between the two periods. Clinical manifestations, co-infections, inflammatory biomarkers, and imaging findings were evaluated to characterize differences in disease presentation between pre- and post-COVID periods. Also, risk factors associated with pediatric hospitalization in the post-COVID period were explored. Results: Marked changes were observed in the epidemiological and clinical profile of pediatric HAdV infection after the COVID-19 pandemic. In the post-COVID period, hospitalized children were younger than outpatients and were more likely to present with respiratory, gastrointestinal, and neurological symptoms. They had higher rates of viral or bacterial co-infections, particularly influenza co-infection, along with moderately increased inflammatory biomarkers and greater pulmonary involvement. In addition, seasonal patterns and age distribution shifted measurably after the COVID-19 pandemic. Despite these changes, the overall clinical severity of pediatric HAdV infection did not show substantial worsening. Conclusion: Pediatric HAdV infection after the COVID-19 pandemic was characterized by a distinct epidemiological and clinical pattern, including altered seasonality, younger age concentration, increased influenza co-infection, and moderately heightened inflammatory responses. However, these changes were not accompanied by a substantial deterioration in overall clinical severity. Continued surveillance is warranted to monitor the evolving post-pandemic profile of pediatric HAdV infection.

In this review we comprehensively discuss organic cation transporter novel 1 (OCTN1), encoded by the SLC22A4 gene as a member in the solute carrier 22 (SLC22) family, which facilitates the cellular transport of diverse cationic and zwitterionic substrates. OCTN1 is highly expressed in many vital organs in humans, where it facilitates absorption and distribution of both endogenous compounds and therapeutic drugs. Among its substrates, ergothioneine (EGT) serves as the primary antioxidant and anti-inflammatory molecule, underscoring the essential role of OCTN1 in cellular defense and inflammation control. Genetic polymorphisms in SLC22A4 significantly alter OCTN1 expression, substrate affinity, and drug pharmacokinetics, with strong associations to susceptibility and treatment outcomes in human diseases. Insights from knockout models revealed that OCTN1 deficiency leads to reduced EGT availability, heightened oxidative stress, and aggravated inflammation, particularly in the tissues such as intestine, liver and lung. Moreover, OCTN1 activity is dynamically regulated by epigenetic modifications, cytokines, and hormones, linking it to immune modulation and disease progression. Put together, OCTN1 plays a defined role via high-affinity EGT transport, while its broader transport capacity and pharmacological relevance remain under investigation, with possible - though not yet established - implications for inflammation-associated biomarker development.

Acute poisoning is a growing challenge to emergency departments (EDs). Our aim is to investigate the recent epidemiological and clinical characteristics of patients with acute poisoning and the impact of the COVID-19 pandemic on the disease pattern. This retrospective study included patients with acute poisoning through the medical records from EDs at three tertiary hospitals in Jiangsu Province, China, from January 2017 to April 2023. Their epidemiological and clinical profiles were investigated and analyzed under each category of poisoning. In parallel, the enrolled patients were also divided into the pre-COVID (January 2017-December 2019) and amid-COVID (January 2020-April 2023) groups to derive the differences between them. For 1,876 patients enrolled, their mean age was 49.5 ± 21.1 years, where the female-to-male ratio (FMR) was 1.1. The most common toxic substances were pesticides (31.6%), drugs (31.1%), and alcohol (17.1%). Predominantly, acute poisoning occurred at domiciliary sites (76.4%) and with intention (52.9%). Inpatients were much older than outpatients (52.0 ± 21.9 years versus 47.6 ± 20.2 years). Amid the COVID-19 pandemic, the patients with acute poisoning became much younger, and the cases of alcohol poisoning became more frequent. With the increasing cases of acute poisoning, the patient admissions to hospital and intensive care unit (ICU) were both decreased. Epidemiological results revealed that the acute poisoning by pesticides and drugs occurred primarily at home and through suicidal attempts. The most susceptible age to a given poisoning may differ, but a working-age group remains the largest population of intentionally or unintentionally poisoned victims. The impact of COVID-19 pandemic on acute poisoning was prominent, which significantly altered the epidemiological and clinical characteristics.

Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model. Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors. Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options. Not applicable.

The infection by the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among the older population induced viral sepsis and put them at high risk of severity and mortality. We retrospectively investigated 268 patients infected with the Omicron variant of SARS-CoV-2 and hospitalized in two tertiary medical centers in Jiangsu Province, China, from December 2022 to January 2023, who met the Sepsis- 3 criteria. Patients were divided into the survivor (n = 111) and non-survivor (n = 157) groups, and their baseline clinical characteristics, including their demographic information, medical history, clinical manifestation, laboratory test results, arterial blood gas profiles and computed tomography (CT) patterns, were compared between the two groups to evaluate the risk factors for in-hospital death caused by viral sepsis. The median age of the patients hospitalized was 78.5 (IQR: 71.3–84.8), and 69.0% of them were male. 45.9% of the patients were aged ≥ 80 years. From illness onset to hospitalization the median length of time was 7 days, while the duration of hospitalization was 10.0 days (IQR: 6.0–20.8) and the stay in the intensive care unit (ICU) was 7.0 days (IQR: 4.0–14.0). The median cycle threshold (Ct) values for ORF1ab and N gene amplification were 30.3 and 29.2, respectively. Hypertension, diabetes, and cardiovascular diseases prevailed in the patients’ comorbidity list. After laboratory parameters, arterial blood gas exchange profiles, and radiological patterns were examined, a substantial impact of multiple organ dysfunctions induced by Omicron subvariant BA.5 infection was observed in both groups. As a result, the Sequential Organ Failure Assessment (SOFA) score was significantly factorial in the in-hospital mortality of older patients with COVID-19 (a fatality rate of 58.6%), consistent with determinants in death from non-viral sepsis. With the Omicron subvariants having lower pathogenicity but higher transmissibility compared to pre-Omicron variant of concern (VOC), the older population remains the most vulnerable to COVID-19 infection, which could lead to sepsis and septic shock, highlighting the importance of timely booster vaccinations.