Objective To explore the efficiency of indocyanine green (ICG) fluorescence imaging-guided hepatectomy and its short-term prognosis in patients with primary liver carcinoma. Methods Retrospective analysis was conducted on 166 patients diagnosed with primary liver carcinoma and admitted to the Department of Hepatobiliary Surgery of Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine from June 2018 to June 2021. Patients were categorized into ICG group (n=72) and non-ICG group (n=94) based on the utilization of ICG during surgery. Moreover, the clinical information of preoperation, intraoperation, and postoperation were collected and compared between the two groups. ICG fluorescence images of the lesions in the ICG group were recorded for analysis. Results ICG fluorescence intensity is associated with the histopathology, differentiation grade of primary liver cancer, and the presence of liver cirrhosis. Hepatocellular carcinoma lesions predominantly displayed partial fluorescence, while intrahepatic cholangiocarcinoma lesions showed circular fluorescence. Well differentiated tumors exhibited complete fluorescence (7/11), moderately differentiated tumors demonstrated partial fluorescence (28/51), and poorly differentiated tumors displayed circular fluorescence (7/10). Most patients with liver cirrhosis exhibited partial fluorescence (18/35) or complete fluorescence (13/35).Compared to the non-ICG group, the ICG group demonstrated higher serum albumin levels on the first (34.6 g/L vs. 31.4 g/L) and the third postoperative days (32.4 g/L vs. 31.2 g/L)(P<0.001). Conversely, the ICG group showed shorter operation time (170 min vs. 210 min), lower rate of intraoperative hepatic portal blockade (9.7% vs. 33.0%), less intraoperative blood loss (400 mL vs. 430 mL), shorter postoperative hospital stay (10 d vs. 14 d), and lower incidence of short-term postoperative complications (4.2% vs. 20.2%) (P<0.05) compared to the non-ICG group. Conclusions ICG fluorescence intensity is associated with the histopathology, differentiation grade of primary liver cancer, and the presence of liver cirrhosis.The judicious application of ICG fluorescence imaging technology alongside surgical techniques holds promise for improving short-term prognosis and expediting the postoperative recovery.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

OBJECTIVE To investigate the transcriptomal charactersistics of the striatum in the chronic social defeat stress(CSDS)model mice by using spatial transcriptome analysis and to address the underlying mechanism of the striatum in regulating depressive states.METHODS The CSDS para-digm was employed to establish a depression-like mouse model.The depressive indicators of behavioral despair,anhedonia,and social disorders were assessed through a battery of tests,including the tail suspension test,forced swim test,sucrose preference test,and social interaction experiments.The control mice and the mice exhibiting CSDS-sensitive depression-like behaviors were selected for spatial tran-scriptome sequencing of the striatal region.This sequencing aimed to identify highly expressed genes,followed by KEGG and GO enrichment analyses using the DAVID database.RESULTS The CSDS mouse model effectively induced behavioral despair,anhedonia and social avoidance(P<0.05,P<0.01).Spatial transcriptome analysis revealed 193 differentially expressed genes in the striatum of normal mice.KEGG and GO analyses indicated that these genes were primarily associated with striatal devel-opment,locomotor behaviors,and drug addiction.They were strongly implicated in signaling pathways such as cyclic adenosine monophosphate,cyclic guanosine monophosphate-protein kinase G,calcium signaling,Ras-related protein 1,and mitogen-activated protein kinase,and synaptic linked to GABAergic and dopaminergic neurons.In contrast,CSDS modeling mice led to the identification of 298 differentially expressed genes in the striatum compared with the normal control mice.These genes were significantly enriched in pathways related to neurodegenerative diseases,including Huntington disease,Alzheimer disease,and Parkinson disease.CONCLUSION Depressive states induced by CSDS are associated with the pathological processes underlying neurodegenerative diseases in the striatum.

Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.

Objective:To conduct a thorough analysis of the clinical characteristics in patients with trisomy 8 syndrome and autoimmune diseases, and to provide a new perspective on the diagnosis and management of the fever of unknown origin (FUO).Methods:Patients who were admitted to Huashan Hospital, Fudan University between July 1st, 2021 and May 1st, 2024 for FUO and subsequently diagnosed with trisomy 8 syndrome with autoimmune diseases were included. In this retrospective cohort study, patients were divided into infection and non-infection group according to the etiological evidence, and the clinical characteristics and treatments were collected and compared between the two groups. Statistical analysis was performed using the Mann-Whitney U test. Results:Among the nine enrolled patients, one case was associated with Behet syndrome (BD) without myelodysplastic syndrome (MDS) and without co-occurring infection, eight cases were associated with MDS, among which six cases had both BD and MDS, one case had allergic pneumonia, and one case had rheumatoid arthritis. Six MDS cases had infections. The C-reactive protein (CRP) level in the infection group was significantly higher than that in the non-infection group(72.39(14.62, 132.70) mg/L vs 3.68(2.30, 10.09) mg/L; Z=1.00, P=0.048). There were no statistically significant differences in other inflammatory markers (such as white blood cell count, platelet count, erythrocyte sedimentation rate, ferritin, and neutrophil CD64 index) between the infection and non-infection groups (all P>0.05). In the infection group, one had bacterial infection, five had fungal infections, including two cases of disseminated aspergillosis, one case of mixed bacterial, fungal, and viral infections, one case of mucormycosis combined with Enterococcus faecalis infection, and one case of pulmonary aspergillosis combined with disseminated Mycobacterium abscessus infection. Among the nine patients, eight patients received immunosuppressive treatment centered on the glucocorticoids and (or) thalidomide, and all six infected patients received the above immunosuppressive treatment based on the anti-infection therapy. Eight of the nine cases were stable and followed up regularly, while one case died due to worsening of illness. Conclusions:Autoimmune diseases associated with trisomy 8 syndrome is rare. In addition to anti-infection treatment, glucocorticoids, thalidomide or other immunosuppressive drugs should be administrated to suppress the inflammatory response in patients with co-infection, and the disease could be well controlled.

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

ObjectiveTo monitor the microbes in urban drinking water in Jiangxi from 2016 to 2020， to analyze the change in microbial qualification rate， and to provide a scientific basis for government decision-making. MethodsAccording to the Standard Examination Method for Drinking Water （GB/T 5750‒2006） and the Standards for Drinking Water Quality （GB 5749‒2006）， the water samples were collected， tested and evaluated for hygienic safety. The chi-square test was used to compare the qualification rates among different water periods， water source types， water supply modes， water samples， treatment processes， and disinfection methods. ResultsA total of 10 584 water samples were collected and examined from 2016 to 2020，with a qualification rate of 97.72%. The qualified rate of the microbiological index increased gradually over the years. There was no statistically significant difference in the microbiological qualification rate of water samples monitored in different water periods （χ²=0.718，P=0.398）， and the qualification rates were 97.85% and 97.60% in dry and abundant water periods respectively. There was a statistically significant difference in the qualification rates of water samples monitored in different water source types （χ²=79.560，P=0.398）， with groundwater having a higher qualification rate of 98.83% than surface water （97.70%）. The microbiological pass rate of water samples differed among different water supply methods （χ²=201.836，P<0.001）. The microbiological pass rates of municipal centralized water supply， self-built centralized water supply and secondary water supply were 97.51%， 88.94% and 96.56% respectively. The microbiological pass rates of water samples differed among different treatment processes. There were differences in the qualification rates of the water samples between different treatment processes（χ²=855.034，P<0.001）， with 98.22%， 67.19%， 95.60% and 53.13% of the conventionally treated， precipitated filtered， disinfected only and untreated water samples， respectively. The differences in the microbiological qualification rates of the monitored water samples between different disinfection methods were statistically significant （χ²=904.993，P<0.001）. Chlorination disinfection， chlorine dioxide disinfection， other disinfection methods and non-disinfected water samples had the pass rates of 98.35%， 98.19%， 84.38% and 60.16%， respectively. ConclusionThe qualified rate of the microbiological index of drinking water in Jiangxi increases year by year， but there are still some drinking water without appropriate disinfectants and water quality treatment processes. There is still a need to strengthen the purification， disinfection and monitoring of drinking water.