Meropenem is one of the most widely used special-grade antimicrobial agents in the treatment of neonatal sepsis.However,its irrational use has led to an increasingly severe problem of bacterial multidrug resistance.The guideline was developed following standardized methods and procedures,and provides 12 recommendations specifically addressing 9 clinical issues.The recommendations cover various aspects of meropenem use in neonates,including timing of administration,recommended dosage,extended infusion,monitoring and assessment,antimicrobial adjustment strategies,treatment duration,and treatment strategies for carbapenem-resistant Enterobacteriaceae infections.The aim of the guideline is to provide evidence-based recommendations and guidance for the rational use of meropenem in neonates with sepsis.[Chinese Journal of Contemporary Pediatrics,2024,26(2):107-117]

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

This article provides an interpretive review of the "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation", which was updated and published by the American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) based on the latest clinical evidence. It delves into the classification and management strategies for atrial fibrillation (AF), grounded in the most current evidence-based medical research. The guideline offers significant updates in various aspects such as the definition and staging of AF, clinical evaluation and treatment, modification of risk factors, prevention of thromboembolism, and management of specific populations. Notably, the introduction of a new staging model for AF and corresponding management strategies stands out, underscoring the importance of prevention and early intervention. This article focuses on the three pillars of integrated AF management—stroke risk assessment, modification of risk factors, and management of specific patient groups, in addition to rate and rhythm control, analyzes their substantial significance in clinical practice and guides clinicians in providing more precise treatment.

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Humans ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Prospective Studies ; Retrospective Studies ; Lymph Nodes/pathology* ; Lymph Node Excision ; Gastrectomy ; Multicenter Studies as Topic

After the implementation of neoadjuvant chemoradiotherapy and total mesorectal excision, lateral local recurrence becomes the major type of local recurrence after surgery in rectal cancer. Most lateral recurrence develops from enlarged lateral lymph nodes on an initial imaging study. Evidence is accumulating to support the combined use of neoadjuvant chemoradiotherapy and lateral lymph node dissection. The accuracy of diagnosing lateral lymph node metastasis remains poor. The size of lateral lymph nodes is still the most commonly used variable with the most consistent accuracy and the cut-off value ranging from 5 to 8 mm on short axis. The morphological features, differentiation of the primary tumor, circumferential margin, extramural venous invasion, and response to chemoradiotherapy are among other risk factors to predict lateral lymph node metastasis. Planning multiple disciplinary treatment strategies for patients with suspected nodes must consider both the risk of local recurrence and distant metastasis. Total neoadjuvant chemoradiotherapy is the most promising regimen for patients with a high risk of recurrence. Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy seemingly improves the local control of positive lateral nodes. However, its impact on the safety of surgery in patients with no response to the treatment or regrowth of lateral nodes remains unclear. For patients with smaller nodes below the cut-off value or shrunken nodes after treatment, a close follow-up strategy must be performed to detect the recurrence early and perform a salvage surgery. For patients with stratified lateral lymph node metastasis risks, plans containing different multiple disciplinary treatments must be carefully designed for long-term survival and better quality of life.
Humans ; Lymphatic Metastasis/pathology* ; Quality of Life ; Neoplasm Staging ; Retrospective Studies ; Lymph Nodes/pathology* ; Rectal Neoplasms/surgery* ; Lymph Node Excision/methods* ; Neoadjuvant Therapy/methods* ; Neoplasm Recurrence, Local/surgery*

OBJECTIVE: To evaluate the molluscicidal activity of surfactin against Oncomelania hupensis, so as to provide the experimental basis for use of Bacillus for killing O. hupensis. METHODS: O. hupensis snails were collected from schistosomiasisendemic foci of Wuhu City on September 2022, and Schistosoma japonicum-infected snails were removed. Then, 60 snails were immersed in surfactin at concentrations of 2, 1, 0.5, 0.25, 0.125 mg/mL and 0.062 5 mg/mL for 24, 48, 72 hours at 26 °C, while ultrapure water-treated snails served as controls. The median lethal concentration (LC₅₀) of surfactin against O. hupensis snails was estimated. O. hupensis snails were immersed in surfactin at a concentration of 24 h LC₅₀ and ultrapure water, and then stained with propidium iodide (PI). The PI uptake in haemocyte was observed in O. hupensis snails using fluorescence microscopy. RESULTS: The mortality of O. hupensis was 5.0% following immersion in surfactin at a concentration of 0.062 5 mg/mL for 24 h, and the mortality was 100.0% following immersion in surfactin at a concentration of 2 mg/mL for 72 h, while no snail mortality was observed in the control group. There were significant differences in the mortality of O. hupensis in each surfactin treatment groups at 24 (χ² = 180.150, P < 0.05), 48 h (χ² = 176.786, P < 0.05) and 72 h (χ² = 216.487, P < 0.05), respectively. The average mortality rates of O. hupensis were 38.9% (140/360), 62.2% (224/360) and 83.3% (300/360) 24, 48 h and 72 h post-immersion in surfactin, respectively (χ² = 150.264, P < 0.05), and the 24, 48 h and 72 h LC₅₀ values of surfactin were 0.591, 0.191 mg/mL and 0.054 mg/mL against O. hupensis snails. Fluorescence microscopy showed more numbers of haemocytes with PI uptake in 0.5 mg/mL surfactintreated O. hupensis snails than in ultrapure water-treated snails for 24 h, and there was a significant difference in the proportion of PI uptake in haemocytes between surfactin-and ultrapure water-treated snails (χ² = 6.690, P < 0.05). CONCLUSIONS Surfactin is active against O. hupensis snails, which may be associated with the alteration in the integrity of haemocyte membrane.
Animals ; Molluscacides/pharmacology* ; Snails ; Schistosoma japonicum ; Lethal Dose 50 ; Water

OBJECTIVE: To analyze the quality of blood smear examinations for malaria parasites in Chenzhou City, so as to provide insights into sustainable consolidation of malaria elimination achievements. METHODS: All positive blood smears from fever patients were irregularly sampled from each county (district) of Chenzhou City from 2018 to 2022 and reexamined, and no less than 3% negative blood smears were reexamined. The preparation, dyeing, cleanliness and microscopic examination results of blood smear were reexamined, and the quality of blood smear reexaminations was assessed using a descriptive statistical method. RESULTS: A total of 13 625 fever patients received blood smear examinations for malaria parasites in Chenzhou City from 2018 to 2022, of which 21 were positive and 13 604 were negative; 687 blood samples were reviewed, and the percentage of negative blood smear reexaminations was 4.90% (666/13 604), with a 63.51% rate of qualified negative blood smears preparation, a 67.87% rate of qualified dyeing and a 76.13% rate of qualified cleanliness, and no missing diagnosis found. There were 21 positive blood smears reexamined, and the proportions of qualified blood smears preparation, dyeing and cleanliness were all 85.71%, with 2 smears mistaking Plasmodium species (9.52%). The percentage of qualified negative blood smears preparation was 51.41% in 2022, which reduced by 31.61% in relative to that (75.17%) in 2019 (χ² = 9.033, P < 0.05), and the percentage of qualified negative blood smears dyeing was 60.19% in 2022, which reduced by 28.82% in relative to that (84.56%) in 2019 (χ² = 19.498, P < 0.05), while the percentage of qualified negative blood smears cleanliness was 62.96% in 2022, which reduced by 28.93% in relative to that (88.59%) in 2019 (χ² = 23.826, P < 0.001). In addition, there were no significant differences in the proportion of qualified negative blood smears preparation (χ² = 0.260, P > 0.05) or dyeing (χ² = 1.094, P > 0.05) among the three years, while a significant difference was detected in the percentage of qualified negative blood smears cleanliness (χ² = 12.175, P < 0.05). CONCLUSIONS No missing diagnosis was seen in blood smear examinations for malaria parasites among fever patients in Chenzhou City after malaria elimination; however, there were reductions in proportions of qualified blood smears preparation, dyeing and cleanliness. Quality control of blood smear examinations is recommended to be reinforced in key regions of Chenzhou City.
Animals ; Humans ; Parasites ; Malaria/prevention & control* ; Plasmodium ; Fever ; Microscopy

OBJECTIVE: To understand the clinical and epidemiological characteristics of human ocular thelaziasis patients in China. METHODS: Case reports regarding human ocular thelaziasis cases in China were retrieved in international and national electronic databases, including CNKI, VIP, CBM, Traditional Chinese Medical Literature Analysis and Retrieval System, Wanfang Database, PubMed and Web of Science from 2011 to 2022. Patients' gender, age, clinical symptoms, treatment, recurrence, site of infections, time of onset, affected eye, affected sites, number of infected Thelazia callipaeda, sex of T. callipaeda and source of infections were extracted for descriptive analyses. RESULTS: A total of 85 eligible publications were included, covering 101 cases of human ocular thelaziasis, including 57 males (56.44%) and 44 females (43.56%) and aged from 3 months to 85 years. The main clinical manifestations included foreign body sensation (56 case-times, 22.49%), eye itching (38 case-times, 15.26%), abnormal or increased secretions (36 case-times, 14.46%), tears (28 case-times, 11.24%) and eye redness (28 case-times, 11.24%), and conjunctival congestion (50 case-times, 41.67%) was the most common clinical sign. The most common main treatment (99/101, 98.02%) was removal of parasites from eyes using ophthalmic forceps, followed by administration with ofloxacin and pranoprofen. In publications presenting thelaziasis recurrence, there were 90 cases without recurrence (97.83%) and 2 cases with recurrence (2.17%). Of all cases, 51.96% were reported in four provinces of Hubei, Shandong, Sichuan, Hebei and Henan, and ocular thelaziasis predominantly occurred in summer (42.19%) and autumn (42.19%). In addition, 56.45% (35/62) had a contact with dogs. CONCLUSIONS The human thelaziasis cases mainly occur in the continental monsoon and subtropical monsoon climate areas such as the Yellow River and the Yangtze River basin, and people of all ages and genders have the disease, with complex clinical symptoms and signs. Personal hygiene is required during the contact with dogs, cats and other animals, and individual protection is required during outdoor activities to prevent thelaziasis.
Animals ; Dogs ; Female ; Humans ; Male ; Bibliometrics ; China/epidemiology* ; Seasons ; Spirurida Infections/epidemiology* ; Thelazioidea ; Eye Diseases/parasitology*

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.
Positron Emission Tomography Computed Tomography ; Radiotherapy Planning, Computer-Assisted/methods* ; Algorithms ; Particle Accelerators ; Biology ; Radiotherapy, Image-Guided/methods* ; Radiotherapy Dosage

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.