Objective To evaluate the clinical efficacy of oral use of Jiawei Puji Xiaodu Granules(mainly composed of Lonicerae Japonicae Flos,Forsythiae Fructus,Taraxaci Herba,Violae Herba,Schizonepetae Herba,Arctii Fructus,Gleditsiae Spina,Paeoniae Radix Rubra,Moutan Cortex,and Phragmitis Rhizoma)combined with external application of Xiaozhong Sanjie Ointment(mainly composed of Scutellariae Radix,Coptidis Rhizoma,Phellodendri Chinensis Cortex,and Gleditsiae Spina,etc.)in the treatment of acute tonsillitis in children,and to observe their effects on the immune function and related inflammatory indexes of the patients.Methods A total of 116 children with acute tonsillitis of heat stagnation in the lung and stomach type were randomly divided into the control group and the observation group,with 58 cases in each group.The control group was treated with Cefixime Dispersible Tablets,while the observation group was treated with Jiawei Puji Xiaodu Granules for oral use and Xiaozhong Sanjie Ointment for external application.Both groups were treated for 14 days and then were followed-up for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,white blood cell(WBC)count,T lymphocyte subset CD3+,CD4+,CD8+ and CD4+/CD8+ levels,and serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6)and C-reactive protein(CRP)in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and time for the disappearance of clinical symptoms were compared between the two groups,and the occurrence of adverse reactions and the recurrence of tonsillitis in the two groups were monitored at the same time.Results(1)During the trial,there were 8 cases falling off in the control group but none case falling off in the observation group,and eventually 50 cases in the control group and 58 cases in the observation group completed the full course of treatment.(2)After 14 days of treatment,the total effective rate of the observation group was 98.28%(57/58),while that of the control group was 90.00%(45/50).The intergroup(tested by rank sum test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the time for the disappearance of sore throat,time for the disappearance of purulent spots,time for subsiding fever and time for the tonsils recovering to normal in the observation group were all significantly shorter than those in the control group(P＜0.05).(4)After treatment,the scores of primary and secondary symptoms and the overall symptom scores in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction of the scores in the observation group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the levels of T lymphocyte subset CD3+,CD4+ and CD4+/CD8+ in the two groups were significantly higher(P＜0.05)while the level of CD8 + was significantly lower(P＜0.05)than those before treatment,and the increase in the levels of CD3+,CD4+ and CD4+/CD8+ and the reduction of the CD8+ level of the observation group were significantly superior to those of the control group(P＜0.05).(6)After treatment,the levels of WBC,TNF-α,IL-1β,IL-6 and CRP in the two groups were significantly lower than those before treatment(P＜0.05),and the reduction in the observation group was significantly superior to that in the control group(P＜0.05).(7)During the treatment period,no skin allergy,nausea,vomiting or other gastrointestinal adverse reactions occurred in the two groups,which showed a high degree of safety.(8)The 6-month follow-up showed that the recurrence rate of tonsillitis in the observation group was 5.17%(3/58),which was significantly lower than that of 24.00%(12/50)in the control group,and the difference was statistically significant(χ2 = 8.330,P＜0.05).Conclusion The efficacy of Jiawei Puji Xiaodu Granules combined with Xiaozhong Sanjie Ointment exert notable curative effect for children with acute tonsillitis of heat stagnation in the lung and stomach type.The combined therapy can significantly shorten the duration of the disease,improve the clinical symptoms of the children and effectively reduce the recurrence rate of tonsillitis.The therapeutic mechanism may be related to the enhancement of the immune function and the inhibition of inflammatory response.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

The conventional oral drug delivery frequently results in the drug elimination before its complete release due to rapid gastric emptying and short gastrointestinal transport time, thus reducing the bioavailability of drug. In order to maintain an effective concentration of drug in the body and maximize its optimal efficacy, the frequency of administrations often needs to be increased. By contrast, gastric retention drug delivery system (GRDDS), as an innovative method of drug delivery, prolongs the retention time of the drug in the stomach and reduces irritation to the gastrointestinal tract. Consequently, it enhances the bioavailability of drug, reduces dosing frequency for patients and improves treatment adherence. In recent years, domestic and foreign studies have been conducted on gastric retention drug delivery systems. Here, we provide a comprehensive overview of the relevant literature published in recent years, examining their current marketing status, various types, as well as in vivo and in vitro evaluation methods.

Aim To explore the molecular mechanism of luteolin against acute lung injury by network phar-macology and molecular docking technology,and to conduct experimental verification.Methods The re-lated targets of luteolin were predicted by PubChem and Swiss Target Prediction databases.Acute lung in-jury-related targets were collected through the Gene-Cards database.Venny 2.1 was used to draw the Venn diagram,and the common targets of drug and disease were obtained.The protein interaction network(PPI)was established by String online platform,and the core targets were screened by Cytoscape 3.8.2 software.The functional enrichment analysis of Gene Ontology(GO)and pathway enrichment analysis of Kyoto Ency-clopedia of Gene and Genome(KEGG)were per-formed on the common targets using the DAVID data-base,and the results were visualized.Finally,molecu-lar docking was performed by Auto Dock software,and the molecular results were visualized by Pymol.The mouse acute lung injury model was constructed.HE staining was used to detect histopathology,and Western blot was used to detect lung tissue related proteins.Results After screening,85 common targets were ob-tained.Among them,the core targets were AKT1,EG-FR,SRC,MMP9,ESR1,PTGS2,etc.GO enrichment analysis obtained 265 biological processes,including signal transduction,protein phosphorylation,and nega-tive regulation of apoptosis.There were 48 cells,main-ly including plasma membrane,cell solute,cytoplasm,etc.There are 107 molecular functions,mainly inclu-ding ATP binding,protein serine/threonine/tyrosine ki-nase activity,protein kinase activity and so on.A total of 92 signaling pathway were obtained by KEGG path-way enrichment analysis,which mainly acted on PI3 K-AKT signaling pathway,ErbB signaling pathway,VEGF signaling pathway,etc.Molecular docking results showed that luteolin had good docking activity with core targets AKT1,EGFR,SRC,MMP9,ESR1,PTGS2,MMP2,GSK3 B,KDR and PARP1.The binding ener-gy of ERS1,GSK3B and MMP2 was lower than-5.0 kal·mol-1,and the affinity with luteolin was stronger.The pathological results of lung tissue showed that lute-olin could inhibit inflammatory infiltration and had a strong anti-inflammatory effect in LPS-induced acute lung injury model in mice.Western blot experiments showed that luteolin might alleviate the inflammatory response by inhibiting the phosphorylation of AKT.Conclusions Luteolin can play an anti-acute lung in-jury role through multi-target and multi-channel mecha-nisms,which may be closely related to the inhibition of AKT phosphorylation.

Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q₁, Q₃) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q₁, Q₃) of 42 (20, 55) and the median exposure period (Q₁, Q₃) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
Male ; Humans ; SARS-CoV-2 ; COVID-19/epidemiology* ; Incidence ; Family Characteristics

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.
Humans ; Cell Cycle ; Multiple Myeloma/genetics* ; Prognosis ; Risk Factors

AIM: To compare the effectiveness and complications of treating rhegmatogenous retinal detachment(RRD)with foldable capsule body(FCB)and scleral buckling(SB).METHODS: The clinical data of 81 patients(82 eyes)with RRD who underwent surgery at our hospital from March 2019 to April 2022 were retrospectively analyzed. The differences in retinal reattachment rate, best-corrected visual acuity, the absorption of subretinal fluid, postoperative discomfort and incidence of complications between the two treatments were compared.RESULTS: The retinal reattachment rate was 96% in the FCB group and 92% in the SB group, with no significant difference between the two groups(P>0.05). The best corrected visual acuity of the affected macular eyes was different in the both groups(P<0.01). Both groups effectively promoted the absorption of subretinal fluid. The operation time of FCB group was 16.50(12.75, 25.00)min, while it was 38.00(36.25, 41.75)min in the SB group(P<0.001). Patients in the FCB group also had significantly lower eyelid swelling and pain symptoms than those in the SB group(P<0.001). The visual analogue scale(VAS)score at 1d after operation was 1.00(0.00, 2.00)in the FCB group and 3.00(2.00, 3.00)in the SB group(P<0.001).CONCLUSION: FCB is a safe and effective surgical method to treat RRD that can alleviate patient's pain. Furthermore, FCB has a significantly shorter operation time and milder postoperative adverse reactions than SB.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.
Humans ; Adult ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/etiology* ; Antilymphocyte Serum/therapeutic use* ; Transplantation, Homologous/adverse effects* ; Adenoviridae Infections/therapy* ; Transplantation Conditioning/adverse effects* ; Retrospective Studies

Abstract: Objective　To understand the clinical manifestations, symptoms, treatment and recovery of neonates infected with Omicron variant (BA.5.1.3) of SARS-CoV-2, and provide a certain reference for subsequent diagnosis and treatment of related diseases. Methods　The clinical manifestations, epidemiology, auxiliary examinations, and treatment processes of the neonate aged 4-day-old who was community-acquired infection of variant BA.5.1.3 in Sanya was retrospectively analyzed. Results　The neonate's mother was identified as a close contact with patients with coronavirus disease 2019 (COVID-19) one hour before delivery, and tested positive for nucleic acid within 24 hours after delivery. But her breast milk, amniotic fluid, placenta, and umbilical cord were not detected for nucleic acid test after delivery. The nucleic acid test of the neonate was negative within 24 hours after birth. Then he was transferred to the hotel for isolation. Before the transfer, the mother and baby stayed in the same room and ate breast milk but the mother did not wear any mask. The neonate didn't have nucleic acid test on the second and third days of his life, and the nucleic acid test of the neonate was positive on the fourth day, negative on the fifth day, and positive on the sixth day. Then he was transferred to the designated hospital of COVID-19 for treatment. The neonate had no cough, no fever, yellow skin, abdominal distension, general breast feeding, and good reaction. On admission, the laboratory examination showed that blood routine examination and electrolyte were normal, and the myocardial enzyme and liver and kidney functions were normal. The bilirubin was significantly increased (449.3 μmol/L). The nucleic acid test of the neonate was positive and his chest imaging results were normal. The treatment measures were mainly isolation, feeding, blue light fading, close monitoring of vital signs, and antiviral drugs were administered. Jaundice subsided and abdominal distension was relieved after 6 d of treatment, and the treatment process was smooth without complications. Conclusions　The results suggest that the neonates are susceptible to Omicron variant BA.5.1.3 and prone to aggregation. The evidence of vertical transmission is insufficient and the clinical symptoms of neonates infected with Omicron variant BA.5.1.3 are mid, with no involvement of organ damage of the heart, liver, kidney, brain, and other organs.