No established antiviral treatment is available for hand-foot-mouth disease recently.Glucocorticoid treatment for severe hand-foot-mouth disease is controversial.Questions about the indication,dosage and course of treatment are still being explored.The indication and efficacy of glucocorticoid are lacked of support of evidence-based medicine.

Objective To investigate the use of glucocorticoid in severe hand-foot-mouth disease in Henan and Sichuan Province and to compare the therapeutic effects of different dose of glucocorticoid.Methods In this multicenter retrospective study,320 cases of severe hand-foot-mouth disease,which were randomly sampled from Jan.to May 2011 in Henan and Sichuan Province were collected.The use of intravenous glucocorticoid was calculated.Accor-ding to the dose of corticosteroids which had been used,these cases were divided into 3 groups:the non-corticosteroids group,the low-dose group and the high-dose group.The cure rate,febrile duration,nervous system involvement duration,time of staying in hospital,vital signs and serum glucose in 3 groups were compared.Results Patients who used intravenous glucocorticoid accounted for 90.9％ (291/320 cases),and only 29 patients had not used (9.1％).The cure rate among 3 groups were not significantly different(P ＞0.05).In the low-dose group and the high-dose group,the nervous system involvement duration,the febrile duration and time of staying in hospital were longer than those in the non-corticosteroids group (all P ＜ 0.05).Comparing the blood pressure among 3 groups on the first day and the third day of hospitalization,the diastolic blood pressure in the high-dose group was much higher than that in other 2 groups on the third day of hospitalization(all P ＜ 0.05).Conclusions Glucocorticoid is generally used in severe hand-foot-mouth disease in Henan and Sichuan Province.The high-dose glucocorticoid is more often used in the situation that fever,nervous system involvement are not relieved.Glucocorticoid can never improve the cure rate in patients with severe hand-foot-mouth disease or shorten the course,relieve clinical symptoms.The therapeutic effects of glucocorticoid in severe hand-footmouth disease are not confirmed.The therapy of high-dose glucocorticoid may increase medicinal side effects.

Objective To study the role of PI3K-Akt-GSK-3β signaling in the apoptosis of renal tubular cells after ischemia-reperfusion injury and the protective mechanism of recombinant human erythropoietin(rHuEPO). Methods The human kidney tubular epithelial cells(HK-2)were cultured in vitro in different conditions as control group with serum, ischemia-reperfusion(IR)group, LY294002 group with LY294002(AKT inhibitor)10 μmol/L 30 minutes before IR treatment, LiCl group with LiCl(GSK-33 inhibitor)20 μtmol/L 30 minutes before IR treatment, rHuKPO group with EPO 20 U/ml 30 minutes before IR treatment, rHuEPO + LY294002 group with EPO 20 U/ml and in the presence of LY294002(10 μmol/L)30 minutes before IR treatment, rHuEPO +LiCl group with EPO 20 U/ml and in the presence of LiCl(20 μmol/L)30 minutes before IR treatment. Akt, GSK-33 and caspase-3 activation were measured by Western blotting. The apoptotic ratio of HK-2 cells was measured by flow cytometry. Cell viability was detected by MTT. Results In comparison with the control group, the apoptotic ratio raised up to 15.20%±1.43%, the expression of Akt activity decreased, GSK-33 activity and caspase-3 activity markedly elevated in IR group(P<0.05). LY294002 group up-regulated the apoptotic ratio(18.20%±2.06%), decreased the expression of Akt activity, increased GSK-33 activity and caspase-3 activity, however, LiCl group down-regulated the apoptotic ratio(12.30%±0.85%), increased the expression of Akt activity, decreased GSK-33 activity and caspase-3 activity compared with IR group(P<0.05). rHuEPO group remarkably decreased the apoptotic ratio(11.10%±1.62%), increased the expression of Akt activity, decreased GSK-33 activity and caspase-3 activity compared with IR group(P<0.05). rHuEPO+LY294002 group elevated the apoptotic ratio(13.40%±1.94%), decreased the expression of Akt activity, increased GSK-33 activity and caspase-3 activity, meanwhile, rHuEPO +LiCl group down-regulated the apoptotic ratio(7.50%±1.31%), increased the expression of Akt activity, decreased GSK-33 activity and caspase-3 activity compared with rHuEPO group(P<0.05). Conclusions PI3K-Akt-GSK-3β signaling pathway is involved in HK-2 cells apoptosis induced by ischemia-reperfusion injury and rHuEPO may be used as a new therapy.

Objective To explore the visinin-like protein-1 (VILIP-1) levels in the blood in the Alzheimer disease (AD) and mild cognitive impairment (MCI) due to AD patients,and also to explore its feasibility as a biomarker for the early diagnosis of AD and for the detection of progression of AD.Methods Fifty-eighty participants were included:20 cases for AD group,19 cases for MCI due to AD group,19 cases for normal control group.The level of VILIP-1 was tested by the ELISA method.Results The level of VILIP-1 in AD group was significantly higher than that in normal control group and MCI due to AD group:(9.0 ± 2.9) ng/L vs.(3.3 ± 1.7) and (6.5 ± 3.1) ng/L,and that in MCI due to AD group was significantly higher than that in normal group,there were statistical differences (P ＜ 0.01).The MMSE score in AD group was significantly lower than that in normal group and MCI due to AD group:(15 ± 3) scores vs.(27 ± 2) and (23 ± 2) scores,and that in MCI due to AD group was significantly lower than that in normal group,there were statistical differences (P ＜ 0.01).The level of VILIP-1 was negatively correlated with MMSE score (r =0.463,P ＜ 0.01),but positively correlated with age (r =0.417,P =0.01).Conclusions With the progression of the disease,the cognitive impairment of the AD patient is decreasing.VILIP-1 increased in the blood of the patients of AD and MCI due to AD.It means that the blood VILIP-1 could be a new and potential biomarker for the early diagnosis of AD,and it may be clinical useful for the early diagnosis and effective detection of AD to some extent.

Objective To evaluate the diagnostic accuracy of half-Fourier single-shot TSE MR cholangiopancreatography (HASTE-MRCP) of 0.5 T MR scanner, and to assess its imaging advantage and clinical value by comparing with 3D-TSE-MRCP MIP. Methods All 95 patients were examined by HASTE-MRCP and 3D-TSE-MRCP with respiratory-triggering (Philips 0.5 T T5-NT). The results, including anatomies and diseases, were evaluated after operation. Results By HASTE-MRCP, common bile ducts, 1-3 branches of hepatic ducts, gallbladder, and pancreatic ducts were demonstrated in 100.0%, 94.7%, 74.1%, and 63.2% of the cases. Stones, malignant diseases, and postoperative stenosis were revealed in 100.0% of the cases. Compared with 3D-TSE-MRCP, the demonstrating rates of 4-5 hepatic ducts,neck of the gallbladders,and calculi,especially mud calculi, were higher in HASTE-MRCP, and there was significant difference between the two ways. Stones displayed as low signal in the bile ducts. Block obstruction and mass contour were revealed in malignant diseases. Conclusion Comparing with 3D TSE-MRCP, HASTE-MRCP was better and faster, especially in serious patients or in cases with small and mud calculus.

PURPOSE: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been shown to play a role in various types of cancer. However, the clinical significance and function of FSTL1 in breast cancer have not been reported. We investigated the role of FSTL1 in breast cancer in this study. METHODS: Enzyme-linked immunosorbent assays, western blot analysis, and reverse transcription polymerase chain reaction were used to monitor the expression of FSTL1 in breast cancer tissue and in serum samples from breast cancer patients. We employed a 4T1 breast cancer model and Fstl1(+/−) mice for in vivo studies. Hematoxylin and eosin staining, western blot analysis, and RNA sequencing were used to analyze the effect of FSTL1 on primary tumor growth and lung metastasis. RESULTS: We demonstrated that the expression of FSTL1 is reduced in both the breast cancer tissue and the serum of breast cancer patients. We showed that reduced levels of FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1 was associated with decreased survival in breast cancer patients. Experiments on the Fstl1(+/−) mouse model established that FSTL1 deficiency had no effect on primary tumor growth, but increased the lung metastases of breast cancer cells, resulting in reduced survival of tumor-bearing mice. RNA sequencing found significantly reduced expression of Egln3 and increased expression of EGFR in Fstl1(+/−) mice. Thus, our results suggest that FSTL1 may affect the expression of EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung metastatic sites. CONCLUSION: In conclusion, we suggest a suppressor role of FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a potential prognostic biomarker and a candidate therapeutic target in breast cancer patients.
Animals ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Enzyme-Linked Immunosorbent Assay ; Eosine Yellowish-(YS) ; Follistatin-Related Proteins* ; Genes, Tumor Suppressor ; Glycoproteins ; Hematoxylin ; Humans ; Lung* ; Mice ; Neoplasm Metastasis ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Reverse Transcription ; Sequence Analysis, RNA

Objective:To evaluate the safety and efficacy of sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy for extensive-stage small cell lung cancer (SCLC).Methods:A retrospective analysis of patients with extensive-stage SCLC admitted to Jiangsu Cancer Hospital from January 2019 to September 2022 was conducted. Patients who achieved effective chemotherapy combined with immunotherapy received sequential consolidation thoracic radiotherapy. The safety was evaluated according to the common terminology criteria for adverse events (CTCAE) 5.0 standard, and the overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier method.Results:A total of 33 patients were enrolled, with a median age of 66 years (range, 50-79 years). The median follow-up time was 20 months (range, 3-33 months). Fifteen patients (46%) had disease progression, and 12 patients (36%) died. The toxicities mainly included leukopenia, thrombocytopenia, radiation esophagitis, anorexia, and fatigue, etc. Six patients (18%) had grade 4 hematological toxicity, mainly leukopenia. One patient (3%) had grade 3 radiation pneumonitis, and 3 patients (9%) had grade 1-2 radiation pneumonitis. No grade 5 toxicity was observed in all patient groups. The median PFS was 12 months (95% CI=3.9-20.1). The 6-month, 1-year, and 2-year PFS rates were 78%, 49.6%, and 35.6%, respectively. The median OS was 23 months (95% CI=15.98-30.01). The 6-month, 1-year, and 2-year OS rates were 86.2%, 74.5%, and 47.2%, respectively. Conclusions:Sequential consolidation thoracic radiotherapy after first-line chemotherapy combined with immunotherapy is a safe protocol for extensive-stage SCLC. It brings survival benefits to patients by increasing PFS and OS rates.

Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.