OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.

Objective To investigate the value of first platelet count(PLT)to respiratory rate(RR)ratio(PLT/RR)on admission in the diagnosis and prognosis of secondary sepsis in pneumonia patients.Methods A total of 100 patients with pneumonia admitted to the First Affiliated Hospital of Army Medical University from May 2023 to August 2024 were selected as subjects.According to the presence or absence of pneumonia sepsis,they were divided into sepsis group(63 cases)and non-sepsis group(37 cases).The secondary sepsis in pneumonia pa-tients were followed up continuously for 30 d.According to the survival situation,they were divided into sur-vival group(54 cases)and death group(9 cases).PLT in peripheral blood was measured,vital signs were col-lected on the first day of admission,and PLT/RR was calculated.The receiver operating characteristic curve was used to evaluate the predictive value of PLT,RR and PLT/RR for secondary sepsis in pneumonia pa-tients.The systemic inflammatory response syndrome(SIRS)score,modified early warning score(MEWS)and quick sequential organ failure assessment(qSOFA)score on admission were calculated,and the clinical predictive value of SIRS score,MEWS and qSOFA score was compared.Results PLT and PLT/RR in sepsis group were lower than those in non-sepsis group(P<0.000 1),RR was higher than that in non-sepsis group(P<0.01).The area under the curve(AUC,95%CI)of PLT,RR and PLT/RR were 0.858(0.785-0.931),0.693(0.589-0.796)and 0.902(0.843-0.962),respectively.The optimal cut-off values were 146.5×109/L,20.5 per minute and 8.075,respectively.The specificity were 8.1%,83.8%and 2.7%,respec-tively.The sensitivity was 33.3%,50.8%and 30.2%,respectively.Compared with the non-sepsis group,the sepsis group had a significantly higher SIRS score(P<0.001),a significantly lower MEWS(P<0.000 1),and no significant difference in qSOFA score between the two groups(P>0.05).The AUC(95%CI)of SIRS score,MEWS and qSOFA score in predicting secondary sepsis in pneumonia patients were 0.717(0.616-0.818),0.748(0.650-0.846)and 0.505(0.389-0.622),respectively.The optimal cut-off values were 4.5,2.5 and 1.5 points,respectively.The specificity were 91.9%,2.7%and 100.0%,respectively.The sensitivity was 42.9%,33.3%and 6.3%,respectively.PLT and PLT/RR in death group were lower than those in sur-vival group(P<0.05),RR was higher than that in survival group(P<0.05).Secondary sepsis in pneumonia patients were followed up for 30 d,Kaplan-Meier survival curve showed that patients with PLT≤138.5×109/L had a lower 30 d survival rate(P=0.007 8).Patients with RR>24.5 per minute had a lower 30 d sur-vival rate(P=0.016 1).Patients with PLT/RR≤6.375 had a lower 30 d survival rate(P=0.002 3).Conclu-sion PLT/RR can be used as a biological index to predict secondary sepsis in pneumonia patients,which is better than SIRS score,MEWS and qSOFA score,and the prognosis of secondary sepsis in pneumonia patients with low PLT/RR is worse.

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Hair follicle (HF), one of the skin appendages, has received a lot of attention to be a new target and pathway for drug delivery. The development of hair follicle targeted drug delivery system (HFTDDS) through percutaneous permeation is particularly important for skin diseases derived from HF such as acne, hair loss, and folliculitis for their on-site action. This review describes the structure and physiological function of HF, the microenvironment of HF, and factors affecting HF permeation. Multiple nanoformulations used to improve the HF permeation and technologies to characterize the HF permeation were introduced. The latest advance of HFTDDS based on nanoformulations were systematically summarized and analyzed in the treatment of acne and hair loss. Finally, the challenges of formulating HFTDDS were discussed. The review is expected to provide some ideas and references for developing delivery systems for treating skin diseases derived from HF.

Objective:To conduct a Meta-analysis on the application effect of information management on safe in-hospital transfer of patients in China.Methods:Using computers to search for randomized controlled trials and quasi experimental studies on the effect of information management on safe in-hospital transfer of patients in China from China National Knowledge Infrastructure, VIP, Wanfang Database, China Biomedical Mediline disc, PubMed, Embase, Web of Science, CINAHL and Cochrane Library. The search period was from establishment of databases to May 17, 2022. Literature screening, quality evaluation and data extraction were conducted independently by two trained researchers. Stata 15.1 software was used for Meta-analysis.Results:A total of 14 articles were included, involving a total of 130 670 patients. The results of Meta-analysis showed that the incidence of adverse event in in-hospital transfer of patients in the information management group was shorter than that in the control group ( OR=0.24, 95% CI: 0.17-0.35, P<0.01), duration of in-hospital tranfer was longer than that in the control group ( WMD=-5.76, 95% CI: -8.30-3.22, P<0.01), and patients' satisfaction ( OR=1.11, 95% CI: 1.05-1.17, P<0.01) and satisfaction of medical personnel responsible for transfer ( OR=1.37, 95% CI: 1.13-1.66, P<0.01) were higher than those of the control group. Conclusions:Information management can effectively control the incidence of adverse events in in-hospital transfer of patients in China, shorten the time required for hospital transfers and improve the satisfaction of patients and medical staff in hospital transfers.

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.
Autoantibodies ; Autoimmune Diseases/diagnosis* ; Connective Tissue Diseases/diagnosis* ; Diagnosis, Differential ; Humans ; Liver

Objective: To prepare graphene oxide (GO)-containing gelatin methacrylate anhydride (GelMA) hydrogel and to investigate the effects of in situ photopolymerized GO-GelMA composite hydrogel in wound vascularization of full-thickness skin defect in mice. Methods: The experimental study method was used. The 50 μL of 0.2 mg/mL GO solution was evenly applied onto the conductive gel, and the structure and size of GO were observed under field emission scanning electron microscope after drying. Human skin fibroblasts (HSFs) were divided into 0 μg/mL GO (without GO solution, the same as below) group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, 5.0 μg/mL GO group, and 10.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the absorbance value was detected using a microplate analyzer after 48 h of culture to reflect the proliferation activity of cells (n=6). HSFs and human umbilical vein vascular endothelial cells (HUVECs) were divided into 0 μg/mL GO group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the migration rates of HSFs at 24 and 36 h after scratching (n=5) and HUVECs at 12 h after scratching (n=3) were detected by scratch test, and the level of vascular endothelial growth factor (VEGF) secreted by HSFs after 4, 6, and 8 h of culture was detected by enzyme-linked immunosorbent assay method (n=3). The prepared GO-GelMA composite hydrogels containing GO of the corresponding final mass concentration were set as 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group to observe their properties before and after cross-linking, and to detect the release of GO after soaking with phosphate buffer solution for 3 and 7 d (n=3). The full-thickness skin defect wounds were made on the back of 16 6-week-old female C57BL/6 mice. The mice treated with in situ cross-linked GO-GelMA composite hydrogel containing GO of the corresponding final mass concentration were divided into 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group according to the random number table, with 4 mice in each group. The general condition of wound was observed and the wound healing rate was calculated on 3, 7, and 14 d of treatment, the wound blood perfusion was detected by laser Doppler flowmetry on 3, 7, and 14 d of treatment and the mean perfusion unit (MPU) ratio was calculated, and the wound vascularization on 7 d of treatment was observed after hematoxylin-eosin staining and the vascular density was calculated (n=3). The wound tissue of mice in 0 μg/mL GO composite hydrogel group and 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was collected to observe the relationship between the distribution of GO and neovascularization by hematoxylin-eosin staining (n=3) and the expression of VEGF by immunohistochemical staining. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey's method. Results: GO had a multilayered lamellar structure with the width of about 20 μm and the length of about 50 μm. The absorbance value of HSFs in 10.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group after 48 h of culture (q=7.64, P<0.01). At 24 h after scratching, the migration rates of HSFs were similar in the four groups (P>0.05); at 36 h after scratching, the migration rate of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with q values of 7.48, 10.81, and 10.20, respectively, P<0.01). At 12 h after scratching, the migration rate of HUVECs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with q values of 7.11, 8.99, and 14.92, respectively, P<0.01), and the migration rate of HUVECs in 5.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group and 1.0 μg/mL GO group (with q values of 7.81 and 5.33, respectively, P<0.05 or P<0.01 ). At 4 and 6 h of culture, the VEGF expressions of HSFs in the four groups were similar (P>0.05); at 8 h of culture, the VEGF expression of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group and 5.0 μg/mL GO group (with q values of 4.75 and 4.48, respectively, P<0.05). The GO-GelMA composite hydrogels in the four groups were all red liquid before cross-linking, which turned to light yellow gel after cross-linking, with no significant difference in fluidity. The GO in the GO-GelMA composite hydrogel of 0 μg/mL GO composite hydrogel group had no release of GO at all time points; the GO in the GO-GelMA composite hydrogels of the other 3 groups was partially released on 3 d of soaking, and all the GO was released on 7 d of soaking. From 3 to 14 d of treatment, the wounds of mice in the 4 groups were covered with hydrogel dressings, kept moist, and gradually healed. On 3, 7, and 14 d of treatment, the wound healing rates of mice in the four groups were similar (P>0.05). On 3 d of treatment, the MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with q values of 10.70, 11.83, and 10.65, respectively, P<0.05 or P<0.01). On 7 and 14 d of treatment, the MPU ratios of wound of mice in the four groups were similar (P>0.05). The MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was significantly lower than that on 3 d of treatment (q=14.38, P<0.05), and that on 14 d of treatment was significantly lower than that on 7 d of treatment (q=27.78, P<0.01). On 7 d of treatment, the neovascular density of wound of mice on 7 d of treatment was 120.7±4.1 per 200 times of visual field, which was significantly higher than 61.7±1.3, 77.7±10.2, and 99.0±7.9 per 200 times of visual field in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with q values of 12.88, 7.79, and 6.70, respectively, P<0.01), and the neovascular density of wound of mice in 1.0 μg/mL GO composite hydrogel group and 5.0 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group (with q values of 5.10 and 6.19, respectively, P<0.05). On 7 d of treatment, cluster of new blood vessels in wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly more than that in 0 μg/mL GO composite hydrogel group, and the new blood vessels were clustered near the GO; a large amount of VEGF was expressed in wound of mice in 0.1 μg/mL GO composite hydrogel group in the distribution area of GO and new blood vessels. Conclusions: GO with mass concentration lower than 10.0 μg/mL had no adverse effect on proliferation activity of HSFs, and GO of 0.1 μg/mL can promote the migration of HSFs and HUVECs, and can promote the secretion of VEGF in HSFs. In situ photopolymerized of GO-GelMA composite hydrogel dressing can promote the wound neovascularization of full-thickness skin defect in mice and increase wound blood perfusion in the early stage, with GO showing an enrichment effect on angiogenesis, and the mechanism may be related to the role of GO in promoting the secretion of VEGF by wound cells.
Anhydrides ; Animals ; Endothelial Cells ; Eosine Yellowish-(YS) ; Female ; Gelatin/pharmacology* ; Graphite ; Hematoxylin ; Humans ; Hydrogels/pharmacology* ; Methacrylates ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; Skin Abnormalities ; Vascular Endothelial Growth Factor A

In the context of the global pandemic of COVID-19, the epidemic intensity, epidemic characteristics and infection risk of influenza have presented new features. COVID-19 and influenza have simultaneously emerged in many regions of the world. COVID-19 and influenza are similar in terms of transmission mode, clinical symptoms and other aspects. There are also similarities in the mechanism of influenza virus and novel coronavirus on cells. At the same time, it is feasible and significant to do a good job in the prevention and control of COVID-19 and influenza. This paper discusses the relevant strategies and measures for the joint prevention and control of influenza and novel coronavirus from the aspects of influenza vaccination to prevent co-infection, simultaneous vaccination of influenza vaccine and novel coronavirus vaccine, etc., and puts forward corresponding thoughts and suggestions, in order to provide scientific support for the formulation of strategies on seasonal influenza vaccine and novel coronavirus vaccination.
Humans ; Influenza Vaccines ; Influenza, Human/epidemiology* ; COVID-19 Vaccines ; COVID-19/prevention & control* ; Seasons ; Vaccination ; SARS-CoV-2

Objective:To establish the grade evaluation method for Codonopsis Radix slices based relative quality constants， in order to provide scientific theoretical basis for grading of Codonopsis Radix slices. Method:Through literature and market research，the main production areas of Codonopsis Radix slices were determined，and 67 batches of Ludangshen slices（52 batches） and Baitiaodang slices （15 batches） were collected. The appearance traits （average quality and average thickness of Codonopsis Radix slices） were observed and measured. According to Chinese Pharmacopoeia （2015 edition）， the extract and the content of Codonopsis pilosula polysaccharide was determined by phenol-sulphoacid method. Then the relative quality constant was calculated，and the results of grade evaluation were evaluated through systematic cluster analysis and correlation analysis. Result:Relative quality constants of 67 batches of Codonopsis Radix slices were between 0.32-2.97. If these samples were divided into three grades：the first-grade relative quality constants were greater than or equal to 2.08，the second grade was greater than or equal to 0.89 but less than 2.08，while the third grade was less than 0.89. The results of systematic cluster analysis showed that 67 batches of Codonopsis Radix slices were clustered into 3 categories，and the results were basically consistent with the classification. The correlation analysis showed a positive correlation between the content of the extracts and the polysaccharide content （P<0.05）. Conclusion:This method links the extrinsic characteristics to the intrinsic quality，and objectively grade Codonopsis Radix slices， so as to provide a basis for its grade standards.