Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective:To analyze the epidemiological features of respiratory syncytial virus (RSV) infection in Beijing, and monitor the sequence variations in RSV glycoprotein (G) gene and clinical features of infected children.Methods:Respiratory tract specimens were collected from children with acute respiratory infection in the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 1, 2023 to December 31, 2023. RSV-positive specimens screened by multiple nucleic acid testing were subjected to PCR to amplify the full-length RSV G gene. A phylogenetic tree was constructed after gene sequencing to analyze RSV subtypes and trace G gene variants. Clinical data were retrieved from the medical record system to analyze the clinical features of children with RSV infection in Beijing.Results:A total of 5 489 respiratory specimens were collected from 3 046 male patients and 2 443 female patients. The average age of the patients was 4.36 years. A total of 589 RSV-positive specimens (10.7%, 589/5 489) were detected with 349 from male patients and 240 from female patients. The average age of children with RSV infection was (2.51±2.78) years and the median age was 0.48 years. RSV had been circulating among children in Beijing since March 2023 with two epidemic peaks in May (24.6%, 122/496) and December (18.2%, 126/693). The predominant subtype of RSV in the first half of 2023 was subtype A, but it was replaced by subtype B from November 2023. Phylogenetic analysis revealed a novel G gene of RSV subtype B (RSV-B-BA9-954bp) with a length of 954 bp, which belonged to a new cluster in the phylogenetic tree. The percentage of patients admitted to the Intensive Care Unit (ICU) was higher in children with new variant of RSV subtype B infection than in those with common RSV subtype B infection [44.1% (15/34) vs 25.2% (31/123), χ 2=4.600, P=0.032], while the counts of white blood cells and the levels of C-reactive protein were lower in the children with new variant infection ( P<0.05). Conclusions:RSV has been prevalent among children in Beijing since March 2023 with two epidemic peaks. The predominant A subtype is gradually replaced by to B subtype. A new variant of RSV B G gene (RSV-B-BA9-954bp) is detected among the children.

Objective:To construct and validate a nomogram model for predicting sepsis-associated acute kidney injury (SA-AKI) risk in intensive care unit (ICU) patients.Methods:A retrospective cohort study was conducted. Adult sepsis patients admitted to the department of ICU of the 940th Hospital of Joint Logistic Support Force of PLA from January 2017 to December 2022 were enrolled. Demographic characteristics, clinical data within 24 hours after admission to ICU diagnosis, and clinical outcomes were collected. Patients were divided into training set and validation set according to a 7∶3 ratio. According to the consensus report of the 28th Acute Disease Quality Initiative Working Group (ADQI 28), the data were analyzed with serum creatinine as the parameter and AKI occurrence 7 days after sepsis diagnosis as the outcome. Lasso regression analysis and univariate and multivariate Logistic regression analysis were performed to construct the nomogram prediction model for SA-AKI. The discrimination and accuracy of the model were evaluated by the Hosmer-Lemeshow test, receiver operator characteristic curve (ROC curve), decision curve analysis (DCA), and clinical impact curve (CIC).Results:A total of 247 sepsis patients were enrolled, 184 patients developed SA-AKI (74.49%). The number of AKI patients in the training and validation sets were 130 (75.58%) and 54 (72.00%), respectively. After Lasso regression analysis and univariate and multivariate Logistic regression analysis, four independent predictive factors related to the occurrence of SA-AKI were selected, namely procalcitonin (PCT), prothrombin activity (PTA), platelet distribution width (PDW), and uric acid (UA) were significantly associated with the onset of SA-AKI, the odds ratio ( OR) and 95% confidence interval (95% CI) was 1.03 (1.01-1.05), 0.97 (0.55-0.99), 2.68 (1.21-5.96), 1.01 (1.00-1.01), all P < 0.05, respectively. A nomogram model was constructed using the above four variables. ROC curve analysis showed that the area under the curve (AUC) was 0.869 (95% CI was 0.870-0.930) in the training set and 0.710 (95% CI was 0.588-0.832) in the validation set. The P-values of the Hosmer-Lemeshow test were 0.384 and 0.294, respectively. In the training set, with an optimal cut-off value of 0.760, a sensitivity of 77.5% and specificity of 88.1% were achieved. Both DCA and CIC plots demonstrated the model's good clinical utility. Conclusion:A nomogram model based on clinical indicators of sepsis patients admitted to the ICU within 24 hours could be used to predict the risk of SA-AKI, which would be beneficial for early identification and treatment on SA-AKI.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-associated acute kidney injury (SA-AKI) is a common organ dysfunction of sepsis, and its incidence and mortality are increasing, which brings heavy economic burden to patients and society. Early diagnosis and effective intervention can block the occurrence and progression of SA-AKI effectively, improve prognosis, and reduce medical costs. Diagnosis on SA-AKI relies on urine volume and serum creatinine, which has the disadvantages of being easily disturbed and delaying. The identification of biomarkers in blood and urine can facilitate diagnosis and provide targeted therapy to enhance the management of SA-AKI. This article reviews the characteristics of a variety of SA-AKI biomarkers that have been found and validated, including pre-damage biomarkers, damage biomarkers and functional biomarkers, and explore the clinical value of newly discovered biomarkers related to the diagnosis and treatment of SA-AKI, such as blood uncoupling protein 2 (UCP2), Sestrin 2 protein and pannexin 1 (PANX1), to provide reference for the early diagnosis and effective treatment of SA-AKI.

Objective:To understand the serotype distribution, drug resistance and molecular characterization of invasive non-typhoid Salmonella (iNTS) in Guangdong Province from 2018 to 2022 and provide scientific evidence for the prevention and treatment of blood flow infection caused by Salmonella. Methods:Serological identification, antimicrobial susceptibility testing, multilocus sequence typing (MLST), and whole genome sequencing were performed on Salmonella isolated from blood and stool samples in Guangdong from 2018 to 2022. Simultaneously, annotated the sequencing results for drug resistance genes and virulence factors by a microbial gene annotation system. Results:The 136 iNTS strains were divided into 25 serotypes, and Salmonella enteritidis accounted for 38.24% (52/136). The OR of other iNTS serotypes were calculated with Salmonella typhimurium as the control. The OR values of Oreninburg, Rysson, and Pomona serotypes were the highest, which were 423.50, 352.92, and 211.75, respectively. The drug resistance rate of iNTS was 0.74%-66.91%, which was lower than that of non-iNTS (3.90%-77.21%). The main iNTS of drug resistance were ampicillin and tetracycline, with resistance rates of 66.91% (91/136) and 50.00% (68/136), respectively, while the resistance rates to ciprofloxacin (5.88%,8/136), ceftazidime (5.88%,8/136), gentamicin (5.13%,7/136) and cefoxitin (0.74%, 1/136) were relatively low. iNTS carried a variety of drug-resistance genes and virulence factors, but no standard virulence factor distribution has been found. MLST cluster analysis showed that iNTS was divided into 26 sequence types, and ST11 accounted for 38.24% (52/136). Conclusions:The iNTS strains in Guangdong were dominated by Salmonella enteritidis, of which three serotypes, Oreninburg, Rison, and Pomona, may be associated with a higher risk of invasive infection during 2018 to 2022 . iNTS was sensitive to clinical first-line therapeutic drugs (cephalosporins and fluoroquinolones), with highly diverse sequences and clear phylogenetic branches. ST11 was the local dominant clone group.

Objective:To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing.Methods:In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6 th, 2023 (6 th week) to May 28 th (21 th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results:There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10 th week, with H1N1 as the predominant one from the 6 th to 9 th week (10.0%-50.0%) and then H3N2 from the 10 th to 16 th week (15.0%-90.0%). HMPV was detected from the 15 th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20 th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15 th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7 th week 10% (6/60), to peak in the 11 th week 31.8% (21/66). H3N2 was detected from the 8 th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12 th week 1.3% (1/80), reaching 30.4% (35/115) at 19 th week. The positive rate of HMPV reached 12.1% (14/116) at 21 th week. Conclusions:In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

The goal of Medical Immunology is to enable students to pay attention to integration of immunology theory with clini-cal practice,be familiar with professional English,consciously pay attention to cutting-edge knowledge,and can learn independently and lifelong.However,existing teaching models lack explanation of clinical disease related events,and arrangement of experimental content and projects is seriously disconnected from clinical practice,scientific research on solving clinical problems is clearly insuffi-cient.We established a"B to B"cycle model for immunology teaching by starting from clinical practical problems(Bedside),return to basic research(Bench),and then solve clinical problem(Bedside),which will comprehensively cultivate senior medical profession-als with clinical competence,scientific research thinking ability,innovative spirit,and international perspective.

Objective To investigate the acute toxicity,irritation,and other effects of Shexiang Anhe hemorrhoid ointment on hemorrhoid-phased model rats by examining the TLR4/p38 MAPK/NF-κB signaling pathway.Methods Sixteen New Zealand rabbits were randomly divided into an intact skin Shexiang Anhe hemorrhoid ointment group,intact skin control group,broken skin Shexiang Anhe hemorrhoid ointment group,and broken skin control group,with four rabbits in each group.In the experimental group,20 g of Shexiang Anhe hemorrhoid ointment(1 g/mL)was evenly applied to an area on the rabbits depleted of hair,and an equal volume of solvent(mixture of glycerol,lanolin,and water)was evenly applied to the area on the backs of the rabbits in the control group once a day for 14 days.Another 40 rats were taken and randomly divided into a normal group,model group,Maillard group,and hemorrhoid cream group,with 10 animals in each group.The cream was applied once a day for 14 days.The acute toxicity of the cream in the intact and broken skin of rabbits was observed by hematoxylin and eosin staining and other method after treatment.In situ photographs were taken of the perianal tissues of rats with hemorrhoids to observe the efficacy of Shexiang Anhe hemorrhoid ointment,and the length and width of the ulcers were measured with vernier calipers to calculate the area.Quantitative real time polymerase chain reaction was used to detect the expression of TLR4,p38 MAPK,and NF-κB mRNA in the perianal tissues of the rats.Results Compared with rabbits in the control groups with intact or broken skin,rabbits in the administered group showed no significant difference in body mass.The mean values for the irritation evaluation points for Shexiang Anhe hemorrhoid ointment on rabbits with broken skin for 1 h,24 h,48 h,and 72 h were 1.5,1,0.5,and 0.25,respectively,showing there was no obvious skin irritation.In the hemorrhoidal rats,Shexiang Anhe hemorrhoid ointment treatment significantly reduced hemorrhoid symptoms after 14 days administration;the ulcer area was significantly smaller(P＜0.05)and TLR4,p38 MAPK,and NF-κB mRNA levels were significantly lower compared with the findings in the model group(P＜0.05).Conclusions Shexiang Anhe hemorrhoid ointment is a safe topical treatment with minimal acute toxicity and irritation to the skin and achieved good efficacy in the treatment of hemorrhoidal rats.Its mechanism of action may be related to the inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway.

Objective To investigate the current status and awareness of pharmaceutical services in hospitals in Guizhou province and to provide a reference for exploring and carrying out pharmaceutical service fees.Methods The questionnaire was designed by the"wjx.cn"website.Three kinds of questionnaires were designed for pharmacists,doctors,nurses,and patients as the research objects,with corresponding differences in some questions,and promoted on WeChat,Dingxiangyuan,and other network platforms.Results A total of 655 questionnaires were collected,and 639 valid questionnaires were recovered,with an effective recovery rate of 97.56%.324 pharmacists(50.70%),82 doctors and nurses(12.83%),233 patients(36.46%)were surveyed.The average approval score of these three groups of respondents on pharmaceutical service fees was 4.67,4.23,and 4.22,respectively(full score:5).Conclusions Overall,pharmacists'professional services have received support from medical staff and patients.However,patients'pharmaceutical service projects currently focus on dispensing services.The recognition of pharmacists'work and the public's awareness of pharmaceutical services can be improved by enhancing the professional ability of pharmacists,strengthening publicity and guidance,and exploring"Internet+pharmaceutical services",etc.,to promote the sustainable development of pharmaceutical services.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.