At present, the treatment of sepsis depends largely on non-specific methods, highlighting an urgent need for novel therapeutic strategies. Stem cells have garnered significant attention in the treatment of various diseases due to their unique biological properties. Stem cells enhance sepsis survival through mechanisms such as reducing bacterial burden, modulating inflammation, and ameliorating organ dysfunction. Recent studies have shown that stem cells can increase the survival rate of sepsis patients through multiple pathways such as reducing the bacterial load of the host, regulating inflammatory homeostasis, and improving multi-organ dysfunction. Their derivatives, exosomes, can also alleviate the imbalanced immune response in sepsis patients. Recent advances in stem cell-based therapies for sepsis were summarized in this paper.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

AIM:To explore the toxicological mechanisms of benzalkonium chloride(BAC)as a preservative in ophthalmic preparations leading to corneal injury in dry eye.METHODS:Network toxicology was employed to obtain the chemical structure of BAC, its toxic targets, and targets associated with dry eye-related corneal injury from databases including PubChem, CTD, ChEMBL, and STITCH. The protein-protein interaction(PPI)networks were constructed using the STRING database to screen key toxicity targets. Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to elucidate the potential biological processes and signaling pathways affected by BAC. Furthermore, molecular docking techniques were employed to validate the binding affinity of BAC to its key targets(IL-6, IL-1β, TNF, and EGF).RESULTS:BAC had a toxicity grade of 4 and exhibited significant eye irritation. A total of 85 common targets of BAC and dry eye corneal damage were screened out, of which 49 were key toxic targets, including TNF, IL-6, TP53, IL-1β, BCL2, etc. KEGG enrichment analysis showed that BAC mainly acted on 7 corneal injury pathways closely associated with corneal injury, such as IL-17, TNF, NF-κB, JAK-STAT, PI3K-Akt, Rap1, and MAPK. The results of molecular docking showed that BAC had stable binding ability to IL-6, IL-1β, TNF, EGF, and other targets(binding energy <0).CONCLUSION:BAC may induce corneal damage in dry eye through multi-target and multi-pathway mechanisms, involving processes such as inflammatory response, apoptosis, disruption of tear film stability, and delayed corneal repair, which suggests that long-term use of ophthalmic preparations containing BAC may aggravate ocular surface damage.

OBJECTIVE To compare the efficacy and safety of different classes of antibacterial agents in hospitalized adult patients with community-acquired pneumonia （CAP）.METHODS PubMed， Embase，the Cochrane Library，Web of Science，CNKI，and Wanfang data were searched from inception to January 1，2026，to identify randomized controlled trials that evaluated different classes of antibacterial agents in hospitalized adults with CAP.After screening the literature， extracting the data， and evaluating the quality of the literature， a network meta-analysis was performed using Stata 18.0.RESULTS A total of 25 studies were included，involving 7 863 patients. In terms of efficacy，compared with carbapenems，penicillins，cephalosporins，macrolides，and pleuromutilins were associated with significantly higher treatment failure rates （ P ＜0.05），carbapenems and traditional tetracyclines were ranked as the top two by the surface under the cumulative ranking curve area （SUCRA）. No statistically significant differences were observed in mortality among the interventions （ P ＞0.05），carbapenems and other quinolones were ranked as the top two by SUCRA. In terms of safety，no statistically significant differences were observed among the interventions in the incidence of adverse events or discontinuation rates （ P ＞0.05）；traditional tetracyclines and novel tetracyclines were ranked as the top two by SUCRA for the incidence of adverse events，while novel tetracyclines and pleuromutilins were ranked as the top two by SUCRA for discontinuation rates.CONCLUSIONS Carbapenems significantly reduced the treatment failure rate in hospitalized adults with CAP. The safety profiles of all antibacterial agents were comparable， with novel tetracyclines showing a more favorable safety profile.

During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective To analyze the epidemiological and pathogenic characteristics of acute respiratory in-fection in Yangpu District of Shanghai,and to provide scientific basis for the prevention and treatment of re-spiratory tract infection.Methods A total of 1 062 patients diagnosed with acute respiratory infection in the hospital from June 2023 to June 2024 were selected as the research objects.The nucleic acid of 13 pathogens in nasopharyngeal swabs of patients was detected and the positive rate was calculated.The positive rate of differ-ent age groups and seasons was analyzed.Results Among 1 062 patients,716 cases were detected positive,the total positive rate was 67.42%,of which 577 cases were single infection,the positive rate was 54.33%.The top five positive pathogens were Mycoplasma pneumoniae(MP,16.48%),human coronavirus(HCOV,9.42%),human rhinovirus(HRV,7.63%),human metapneumovirus(HMPV,5.46%)and parainfluenza vi-rus(HPIV,3.39%).A total of 139 cases were infected with multiple pathogens,with a positive rate of 13.09%.MP,HRV,and HCOV were the dominant pathogens,which were prone to multiple infections.A to-tal of 139 cases were infected with multiple pathogens,with a positive rate of 13.09%.MP,HRV,and HCOV were the dominant pathogens,which were prone to multiple infections.The total positive rate of respiratory pathogens in children was 86.38%,the positive rates of single infection and multiple infection were 65.12%and 21.26%,respectively,which were significantly higher than those in other age groups(P<0.05).Among the 577 children with single infection,MP and HRV were the main pathogens in children,MP and HCOV were the main pathogens in young and middle-aged patients,and HCOV and HRV were the main pathogens in the elderly patients.The total positive rate of pathogens was the highest in winter(69.88%),and the lowest in summer(49.54%).HRV had the highest positive rate in spring,HCOV had the highest positive rate in summer,MP had the highest positive rate in autumn,and influenza virus(including influenza A virus,influen-za A/H3N2 virus,influenza B virus)had the highest positive rate in winter(P<0.05).Conclusion MP,HCOV,HRV,HMPV and HPIV are the top five pathogens of acute respiratory tract infection in Yangpu dis-trict of Shanghai.The etiological characteristics were related to age and seasonality of patients.

Objective To investigate the expression and clinical significance of B7-H5 in patients with chro-nic hepatitis B and hepatitis B virus(HBV)-related hepatocellular carcinoma.Methods Enzyme-linked immu-nosorbent assay(ELISA)was used to detect the serum levels of B7-H5 in 104 patients with chronic hepatitis B,28 patients with HBV-related hepatocellular carcinoma and 35 healthy controls.And statistical methods were used to analyze the difference,correlation and diagnostic value of the results.Results The serum levels of B7-H5 in patients with HBV-related hepatocellular carcinoma,patients with chronic hepatitis B and healthy subjects were statistically different(P＜0.05),and the level from high to low was HBV-related liver cancer patients,chronic hepatitis B patients,healthy subjects.The serum level of B7-H5 in chronic hepatitis B pa-tients with negative HBV-DNA was significantly higher than that in healthy subjects(P＜0.01).The level of B7-H5 in patients with chronic hepatitis B was positively correlated with HBV-DNA load(P＜0.05).And the level of B7-H5 in patients with HBV-related hepatocellular carcinoma was positively correlated with HBsAg,HBeAg and AFP levels(P＜0.05).In addition,B7-H5 had diagnostic value for chronic hepatitis B and HBV-related hepatocellular carcinoma(P＜0.01),and the diagnostic value for HBV-related hepatocellular carcino-ma was higher than that for chronic hepatitis B.The level of B7-H5 in patients with HBV-related hepatocellu-lar carcinoma after surgery was significantly lower than that before surgery(P＜0.05).Conclusion Serum levels of B7-H5 is related to the progression of CHB and HBV-related hepatocellular carcinoma,and can be considered as an effective detection index for the auxiliary diagnosis and the judgment of postoperative condi-tion of CHB and HBV-related hepatocellular carcinoma.