ObjectiveTo investigate the infection characteristics of respiratory syncytial virus (RSV) in children with acute respiratory tract infection (ARI) in Pudong New Area, Shanghai, from 2013 to 2023, so as to provide an evidence for the prevention and control of RSV in Shanghai. MethodsChildren who sought medical care at sentinel healthcare facilities in Pudong New Area, Shanghai, between January 2013 and December 2023 and met the case definition of ARI were included in the study. Nasopharyngeal swab samples were collected and tested for viral pathogens using real-time fluorescene PCR, and the clinical information of whom was collected simultaneously. ResultsA total of 4 980 children were included in the ARI surveillance, among whom 231 tested positive for RSV, with an overall detection rate of 4.64%. Of these, 106 cases were type A and 125 were type B. From 2013 to 2023, the detection rate of RSV in children showed an overall trend of initial increase followed by a decline, with higher detection rates in autumn and winter and lower rates in spring and summer. The RSV detection rate gradually decreased with age, with the highest rate observed in children <1 year old, accounting for 16.33% (80/490) of RSV-detection cases. Cough was the most common clinical symptom. Among the RSV-positive cases, 36 involved co-infection with another virus, 6 co-infected with three viruses, and 1 with mixed infection of four viruses. The most frequent co-infection was RSV and human coronavirus. ConclusionChildren under 1 year of age are more susceptible to RSV infection, with cough being the predominant symptom. RSV infection in Pudong New Area, Shanghai, mainly occurs in winter. Targeted prevention and control measures should be taken for children under 1 year old during the winter season to reduce the risk of both RSV infection and co-infection with human coronavirus and influenza virus.

Naringenin (4,5,7-trihydroxyflavonoid) is a naturally occurring bioflavonoid found in citrus fruits, which plays an important role in metabolic syndrome, neurological disorders, and cardiovascular diseases. However, the pharmacological mechanism and biological function of naringenin on anti-angiogenesis and anti-tumor immunity have not yet been elucidated. Our study firstly demonstrates that naringenin inhibits the growth of hepatocellular carcinoma (HCC) cells both in vivo and in vitro. Naringenin diminishes the ability of HCC cells to induce tube formation and migration of human umbilical vein endothelial cells (HUVECs) and suppresses neovascularization in chicken chorioallantoic membrane (CAM) assays. Meanwhile, in vivo results demonstrate that naringenin can significantly upregulate level of CD8⁺ T cells, subsequently increasing the level of immune-related cytokines in the tumor immune microenvironment. Mechanistically, we found that naringenin facilitate the K48-linked ubiquitination and subsequent protein degradation of vascular endothelial growth factor A (VEGFA) and mesenchymal-epithelial transition factor (c-Met), which reduces the expression of programmed death ligand 1 (PD-L1). Importantly, combination therapy naringenin with PD-L1 antibody or bevacizumab provided better therapeutic effects in liver cancer. Our study reveals that naringenin can effectively inhibit angiogenesis and anti-tumor immunity in liver cancer by degradation of VEGFA and c-Met in a K48-linked ubiquitination manner. This work enlightens the potential effect of naringenin as a promising therapeutic strategy against anti-angiogenesis and anti-tumor immunity in HCC.

ObjectiveTo investigate the epidemiological characteristics of human parainfluenza virus (HPIV) in Pudong New Area, Shanghai, and to provide a basis for the prevention and control of HPIV infections in this area. MethodsA total of 8 180 cases with acute respiratory infection (ARI)/influenza-like illness (ILI) attending the fever outpatient clinics, pediatric outpatient clinics, respiratory outpatient clinics, pediatric wards, emergency departments, respiratory wards, and intensive care units (ICUs) and other monitoring departments in 9 sentinel hospitals in Pudong New Area from 2017 to 2022 were selected as the research subjects, and their nasopharyngeal/ throat swabs were collected. Polymerase chain reaction (PCR) method was performed for testing the respiratory virus such as influenza virus, human adenovirus, human parainfluenza virus, respiratory syncytial virus (RSV), human enterovirus, rhinovirus, et al. HPIV serotypes were analyzed, and the detection rates of HPIV were compared between different times, seasons, and population groups. ResultsThe overall HPIV detection rate of ARI/ILI cases in Pudong New Area was 3.73% (305/8 180) in 2017‒2022, with HPIV-3 being the predominant serotype. The detection rate of HPIV decreased significantly in 2017‒2022, peaking at 7.66% (99/1 293) in 2017 and falling to 0.80% (13/1 617) in 2021. Statistically significant differences were observed in HPIV detection rates across different years (χ²_trend=80.037, P_trend<0.001). The detection rate was higher in 2017‒2019 than that in 2020‒2022 (χ²_trend=38.990, P_trend<0.001). HPIV exhibited seasonal patterns in 2017‒2019, with higher detection rates in summer and autumn and lower in spring and winter, whereas no seasonal patterns were observed in 2020‒2022. Children aged <6 years had the highest detection rate (7.07%, 139/1 967), followed by adults aged ≥60 years (4.78%, 85/1 779). Statistically significant differences were observed in the detection rates of HPIV among different age groups (χ²=111.210, P<0.001). Symptoms of HPIV infection were predominantly cough, fever, and runny nose in pre-school children, fever, cough, and sore throat in school-age children, and adults, and cough, expectoration, and fever in the elderly. ConclusionThe HPIV detection rate in Pudong New Area was low in 2017‒2022. The seasonal pattern of HPIV circulation in Pudong New Area disappeared in 2020‒2022 due to the influence of infectious disease epidemics. Young children and the elderly should be prioritized in HPIV prevention and control efforts.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

The particularity of children's physiology and pathology determines that doctors should pay special attention to nursing in the process of treating pediatric diseases. This article discussed the dosage form and taking characteristics of pediatric prescriptions in Tai Ping Sheng Hui Fang from the aspects of dosage form and quantity, decoction, dosage, temperature, time, frequency and degree. It has been concluded that Tai Ping Sheng Hui Fang is rich in dosage forms, both internal and external treatment; paying attention to the care of the spleen and stomach, taking medicine in a light and specialized manner, and emphasizing the end of the disease; the way of taking medicine conforms to the physiological and pathological characteristics of children.

Cannabinoid type 1 receptor(CB1R)is one of the most widely studied endocannabinoid receptors in recent years,which is expressed in both central and peripheral nerve systems.CBIR is located in the presynaptic membrane,and regulates the release of neurotransmitters through retrograde inhibitory synaptic transmission,which is an effective target for the treatment of pain.Activation of CB1R has analgesic effect on injurious,pathological,and inflammatory pain,and antagonism of CB1R can cause pain sensitization.This article describes CB1R from the aspects of structure and function,signal transduction,and analgesic mechanism,so as to provide reference for further understanding the pathophysiology of pain and exploring better pain treatment methods.

In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.