Objective: To analyze the etiological surveillance results of influenza-like illness (ILI) cases in Jiangsu Province, and investigate the distribution characteristics of different influenza virus types, so as to provide the evidence for improving influenza prevention and control measures. Methods: Influenza laboratory testing data for sentinel surveillance of ILI cases in Jiangsu Province from 2019 to 2024 were collected through the China Influenza Surveillance Information System. The positive detection rate of influenza virus was calculated, and descriptive analysis was performed to characterize the distribution of different influenza virus types. Using the farthest neighbor linkage method, influenza virus positive detection rates clustering was analyzed by year and week. Clusters were defined based on inter-cluster distance, and the intensity of the positive detection rate was visualized through color gradients in the clustering heatmap. Results: From 2019 to 2024, a total of 183 878 ILI specimens were collected in Jiangsu Province. Among them, 20 059 specimens tested positive for influenza virus, corresponding to an overall positive detection rate of 10.91%, and an average annual positive detection rate of 10.89%. The primary circulating influenza virus types were influenza A H3N2 subtype, accounting for 40.92%, followed by influenza B Victoria linage at 34.00%, and influenza A H1N1 subtype at 24.80%. Influenza B Yamagata linage was not detected throughout the five-year period. Influenza A H3N2 subtype predominated during two distinct periods: from January to March 2019, and from June 2022 to December 2023. Influenz B Victoria linage was the dominant type from April 2019 to May 2022 and again from January to April 2024. Influenza A H1N1 subtype emerged as the primary type from May to December 2024. Year-based clustering analysis grouped the annual positive detection rates from 2019 to 2024 into three clusters. The closest cluster distance was observed between 2019 and 2024. The highest annual positive detection rate occurred in 2023. Both influenza A H3N2 and H1N1 subtype each formed a single cluster, with their peak positive detection rates also recorded in 2023. Influenza B Victoria lineage was separated into two clusters, with its highest positive detection rate occurring in 2020. Week-based clustering analysis revealed that influenza virus detection was concentrated in weeks 47 to 52 and weeks 1 to 15. More specifically, the positive detection rates for influenza A H3N2 subtype peaked during weeks 30 to 34 and weeks 42 to 52; for influenza A H1N1 subtype, during weeks 9 to 15 and weeks 51 to 52; and for influenza B Victoria lineage, during weeks 1 to 11 and weeks 50 to 52. Conclusions From 2019 to 2024, the average annual positive detection rate of influenza virus in Jiangsu Province remained relatively low. Influenza activity characterized by the alternating circulation of influenza A H1N1 subtype, influenza A H3N2 subtype, and influenza B Victoria linage. It is necessary to maintain the surveillance sensitivity for the influenza B Yamagata lineage.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo analyze the epidemiological characteristics of 21 respiratory pathogens in influenza-like illness (ILI) cases in Jing’an District, Shanghai in 2024, and to provide a scientific basis for the prevention and control of respiratory infectious diseases. MethodsData of1 907 ILI cases at four sentinel hospitals in Jing’an District were collected from January to December 2024. Nasopharyngeal swab samples were collected and tested for 21 respiratory pathogens using polymerase chain reaction (PCR) methods. Chi-square test and Cochran-Armitage trend test were used for data analyses. ResultsAmong the 1 907 ILI cases, 1 340 were tested positive (70.27%), including 1 160 (60.83%) virus-positive cases, 424 (22.23%) bacteria-positive cases , and 86 (4.51%) positive cases of other pathogens (fungi, mycoplasma, and chlamydia). The top five viruses by detection rate were: influenza virus (14.84%), SARS-CoV-2 (14.47%), rhinovirus (12.69%), adenovirus (7.08%), and parainfluenza virus (6.71%). The top two bacteria by detection rate were Streptococcus pneumoniae (14.47%) and Haemophilus influenzae (10.33%). Among other pathogens (fungi, mycoplasma, and chlamydia), Mycoplasma pneumoniae showed the highest detection rate (4.30%). In terms of age distribution, statistically significant differences were observed in the detection rates of SARS-CoV-2, Legionella, and Klebsiella pneumoniae (P<0.05), with the highest rates found in individuals aged 65 years and above. Statistically significant differences were also found in the detection rates of rhinovirus, adenovirus, enterovirus, common coronavirus, respiratory syncytial virus, bocavirus, parainfluenza virus, human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae among different age groups (P<0.05), all showing the highest detection rates in the 0‒<15 years age group. In terms of seasonal distribution, SARS-CoV-2, adenovirus, parainfluenza virus, enterovirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae showed epidemic peaks in summer; rhinovirus, common coronavirus, bocavirus, and Klebsiella pneumoniae had higher detection rates in autumn. Influenza virus exhibited a peak incidence during winter, while human metapenu-movirus peaked in winter and spring. Significant differences in co-infection detection rates were observed among age groups, with the rate in children aged 0‒<15 years (34.81%) being the highest. The co-infection detection rate was higher in males than in females (P=0.019). Both the single-pathogen detection rate and the co-infection detection rate (P<0.001) varied significantly across seasons: the single-pathogen detection rate was highest in winter (62.06%), while the co-infection detection rate peaked in summer (31.20%) and was lowest in winter (14.52%). ConclusionBased on detection rates, the main pathogens in the ILI population of Jing’an District, Shanghai, 2024 were influenza virus, SARS-CoV-2, rhinovirus, adenovirus, parainfluenza virus, common coronavirus, enterovirus, Human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. Pathogen detection rates varied by age and season. Coinfection rates were much higher in children than in adults, higher in males than in females, and peaked in summer while being lowest in winter.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective:To develop the Amputation Scale for Severe Open Pelvic Fractures and explore its application value in patients with severe open pelvic fractures.Methods:A total of 27 patients with severe open pelvic fractures who underwent surgical treatment in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2010 to January 2023 were retrospectively analyzed. There were 15 males and 12 females, aged 38.6±11.6 years (range, 13-65 years). There were 13 cases of traffic injuries, 10 cases of fall from height injuries, and 4 cases of mechanical crushing injuries; 20 cases were admitted to the hospital in emergency, and 7 cases were transferred from other hospitals. All fracture types were Tile C, including 14 cases of Tile C1, 8 cases of Tile C2, and 5 cases of Tile C3. There were 16 cases of genitourinary system injury, 8 cases of anal or rectal injury, 12 cases of abdominal injury, 9 cases of chest injury, and 6 cases of craniocerebral trauma. The mangled extremity severity score (MESS) and the Amputation Scale for Severe Open Pelvic Fractures were used to evaluate whether amputation was performed. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the two evaluation methods were calculated.Results:Among the 27 patients, 21 cases were treated with pelvic external fixator to control the volume, 16 cases were treated with gauze packing to stop bleeding, 8 cases were treated with temporary abdominal aorta occlusion, and 12 cases were treated with laparotomy because of abdominal injury. Seven of the 27 patients died, with a mortality rate of 26%. In 12 cases of one-stage amputation, 3 cases died, including 1 case died of multiple organ failure syndrome, 1 case died of gastrointestinal bleeding on the 7th day after amputation, and 1 case died of severe infection on the 4th day after amputation. Among the 15 cases of one-stage limb salvage, 4 cases died, of which 2 cases of second-stage amputation died of infection on the 5th day after one-stage limb salvage, and 1 case of one-stage limb salvage died of limb necrosis on the 3rd day after one-stage limb salvage. Two patients died of multiple organ failure syndrome. The MESS score of 27 patients was 6(6, 8) points (range, 6-13 points), and the Amputation Scale for Severe Open Pelvic Fractures score was 9.6±1.8 points (range, 6-14 points). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MESS were 66.7%, 50%, 40%, 75% and 56%, respectively, while those of Amputation Scale for Severe Open Pelvic Fractures were 80%, 89%, 73%, 88% and 82%, respectively. The specificity and accuracy of MESS were significantly lower than those of Amputation Scale for Severe Open Pelvic Fractures ( P<0.05). All 20 patients who survived were followed up for 23.6±7.5 months (range, 11-37 months). Five cases had soft tissue infection at the stump of amputation, which were treated with debridement, and 3 cases underwent skin grafting, and the stump healed well at the last follow-up. Conclusion:The Amputation Scale for Severe Open Pelvic Fractures is better than MESS in the assessment of early amputation in patients with severe pelvic fractures.

OBJECTIVE:There are many kinds of biological scaffolds used for pulp revascularization in clinical practice,and the difference of efficacy between different scaffolds is controversial.The efficacy of nine kinds of biological scaffolds in endodontic revascularization was evaluated by Bayesian network meta-analysis.METHODS:The computer was used to search the literature in CNKI,VIP,WanFang,China Biomedical Literature Service System,PubMed,Cochrane Library,Web of Science,Embase,and Scopus databases.Randomized controlled trials of different biological scaffolds for the treatment of pulp revascularization in young permanent teeth meeting inclusion criteria were collected from each database up to April 1,2024.Two researchers sifted through the literature,data collection,sorting and extraction were completed independently,and the quality of the included literature was assessed for risk of bias.A network meta-analysis was performed using BUGSnet1.1.1 package of R4.2.0 software.RESULTS:A total of 22 studies with 926 affected teeth and 9 different interventions were included in this study.The results of network meta-analysis showed that:(1)Clinical success rate(primary goal):platelet-rich fibrin was superior to blood clot[OR=1.45,95％CI(0.32,2.69)],and the top three ranking results were:concentrated growth factor(82.77％)＞platelet-rich fibrin(75.38％)＞modified platelet-rich fibrin(62.39％).(2)Increased root length(secondary goal):There was no difference among the 7 biological scaffolds at 1-6 months of follow-up(P＞0.05),the top 3 ranking results of rank probability were:concentrated growth factor(86.25％)＞platelet-rich plasma(53.76％)＞platelet-rich fibrin(51.11％).When followed up for＞6 months and＜12 months,concentrated growth factor was superior to blood clot[MD=9.59,95％CI(0.52,18.40)],the top 3 ranking results of rank probability were:concentrated growth factor(92.42％)＞platelet-rich plasma(56.03％)＞platelet-rich fibrin(55.76％).When followed up for more than 12 months,concentrated growth factor was superior to modified platelet-rich fibrin[MD=11.01,95％CI(0.02,22.72)],the top 3 ranking results of rank probability were:concentrated growth factor(86.95％)＞platelet-rich fibrin(68.61％)＞blood clot combined with collagen(52.5％).(3)Increased root wall thickness(secondary goal):at 1-6 months of follow-up,platelet-rich fibrin was superior to blood clot[MD=11.37,95％CI(4.74,17.71)],the top 3 ranking results of rank probability were:platelet-rich fibrin(93.66％)＞concentrated growth factor(63.11％)＞modified platelet-rich fibrin(50.48％).At＞6 months and＜12 months of follow-up,there was no difference among the 6 biological scaffolds(P＞0.05),the top 3 ranking results of rank probability were:modified platelet-rich fibrin(73.63％)＞platelet-rich fibrin(62.36％)＞concentrated growth factor(56.25％).When followed up for more than 12 months,there was no difference among the 9 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(81.9％)＞platelet-rich plasma(62.67％)＞modified platelet-rich fibrin(59.49％).(4)Pulp vitality(third-level goal):there was no difference among the 6 biological scaffolds(P＞0.05),and the top 3 ranking results of rank probability were:blood clot combined with collagen(84.22％)＞concentrated growth factor(67.71％)＞platelet-rich fibrin(48.79％).CONCLUSION:Existing evidence shows that the clinical success rate of different scaffolds is higher in pulp revascularization,among which platelet-rich fibrin is better than blood clots.In terms of comprehensive comparison of root length and root wall thickness increase,concentrated growth factor performs best in the follow-up period of 1-6 months and＞6 months and＜12 months,while blood clot combined with collagen performs best after follow-up of more than 12 months;concentrated growth factor performs outstandingly in all levels of goals,and may be more conducive to the continued development of the tooth root than other scaffolds,and has great potential in pulp regeneration treatment.Limited by the quality and quantity of literature,the above conclusions still need to be verified by more high-quality studies.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

Objective To investigate the effect and mechanism of melatonin on the anoikis of melanoma cells.Methods The drug concentration of melatonin inhibiting melanoma cell line B16-F10 was optimized based on the effect on CCK-8 assay.An anti-anoikis of melanoma cell model was developed and divided it into four groups:The blank control group,the TrkB activator group,the melatonin group and the melatonin+TrkB activator group.Calce-in AM/EthD-1 fluorescence double staining was used to detect the anoikis of melanoma cells.Reactive oxygen spe-cies were detected using the fluorescent probe DCFH-DA.Western blot was used to detect the expression of Nrf2 protein and TrkB protein in each group.Results Melatonin significantly inhibited the proliferation of melanoma cells in a time-and dose-dependent manner with IC50 of 1×10-7 μmol/L.Its inhibitory effect was found to be related to in-duction of anoikis of melanoma cells.Melatonin could upregulate the generation of cellular reactive oxygen species(P<0.05),while addition of TrkB activator antagonized this effect.Melatonin could reduce the expression of Nrf2 protein and TrkB protein in melanoma cells(P<0.05),and the addition of TrkB activator could inhibite the effect of melatonin on the expression of Nrf2 protein and TrkB protein(P<0.05).Conclusions Melatonin can inhibit the pro-liferation of melanoma cell line B16-F10 through the mechanism of inducing anoikis.