ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Objective To investigate the neuroprotective effects and mechanisms of the alcoholic extract of the Yi drug(Rubia yunnanensis)on the Alzheimer's disease(AD)model of Caenorhabditis elegans(C.elegans).Methods Based on a transgenic C.elegans model of AD,the efficacy and mechanism of alcoholic extracts of Rubia yunnanensis against β-amyloid(Aβ)-induced toxic effects were explored.C.elegans were synchronized and divided into a control group and low and high dose groups of the alcoholic extract of Rubia yunnanensis to study the effects of the alcoholic extract of Rubia yunnanensis on C.elegans paralysis,lifespan,lipofuscin levels,behavior,growth and development,heat stress and oxidative stress,ROS levels,and Aβ aggregation,as well as the key transcription factors in the insulin/insulin-like growth factor 1 signaling pathway were investigated by GFP reporter gene worm assay and RNAi assay DAF-16 expression.Results Compared with the Control group,the intervention of the alcoholic extracts of Rubia yunnanensis could effectively improve the paralyzed phenotype of C.elegans(P<0.001),prolong the lifespan of C.elegans and reduce the level of lipofuscin in C.elegans significantly(P<0.001),improve the mobility of C.elegans significantly(P<0.001),and improve its resistance to oxidative stress and heat stress damage significantly(P<0.001),and reduce the level of ROS in C.elegans significantly(P<0.001),and reduce the deposition of Aβ protein in the head of C.elegans significantly(P<0.01),and had no effect on the growth and development of C.elegans(P>0.05),and also promoted the nuclear translocation of DAF-16 in the reporter gene C.elegans TJ356,and the effect of the alcoholic extracts of Rubia yunnanensis in delaying the degree of paralysis of C.elegans was lost after silencing the expression of C.elegans DAF-16 by RNAi,whereas the L4440 empty vector control group in the administration of Rubia yunnanensis alcohol extract significantly reduced the level of C.elegans paralysis(P<0.001).Conclusion The alcoholic extract of Rubia yunnanensis can significantly ameliorate the paralyzed phenotype in the C.elegans model of Alzheimer's disease with certain antioxidant,anti-aging and anti-Aβ protein activities,and the mechanism may be related to the activation of DAF-16,a downstream transcription factor of the insulin signaling pathway.

Objective To investigate the neuroprotective effects and mechanisms of the alcoholic extract of the Yi drug(Rubia yunnanensis)on the Alzheimer's disease(AD)model of Caenorhabditis elegans(C.elegans).Methods Based on a transgenic C.elegans model of AD,the efficacy and mechanism of alcoholic extracts of Rubia yunnanensis against β-amyloid(Aβ)-induced toxic effects were explored.C.elegans were synchronized and divided into a control group and low and high dose groups of the alcoholic extract of Rubia yunnanensis to study the effects of the alcoholic extract of Rubia yunnanensis on C.elegans paralysis,lifespan,lipofuscin levels,behavior,growth and development,heat stress and oxidative stress,ROS levels,and Aβ aggregation,as well as the key transcription factors in the insulin/insulin-like growth factor 1 signaling pathway were investigated by GFP reporter gene worm assay and RNAi assay DAF-16 expression.Results Compared with the Control group,the intervention of the alcoholic extracts of Rubia yunnanensis could effectively improve the paralyzed phenotype of C.elegans(P<0.001),prolong the lifespan of C.elegans and reduce the level of lipofuscin in C.elegans significantly(P<0.001),improve the mobility of C.elegans significantly(P<0.001),and improve its resistance to oxidative stress and heat stress damage significantly(P<0.001),and reduce the level of ROS in C.elegans significantly(P<0.001),and reduce the deposition of Aβ protein in the head of C.elegans significantly(P<0.01),and had no effect on the growth and development of C.elegans(P>0.05),and also promoted the nuclear translocation of DAF-16 in the reporter gene C.elegans TJ356,and the effect of the alcoholic extracts of Rubia yunnanensis in delaying the degree of paralysis of C.elegans was lost after silencing the expression of C.elegans DAF-16 by RNAi,whereas the L4440 empty vector control group in the administration of Rubia yunnanensis alcohol extract significantly reduced the level of C.elegans paralysis(P<0.001).Conclusion The alcoholic extract of Rubia yunnanensis can significantly ameliorate the paralyzed phenotype in the C.elegans model of Alzheimer's disease with certain antioxidant,anti-aging and anti-Aβ protein activities,and the mechanism may be related to the activation of DAF-16,a downstream transcription factor of the insulin signaling pathway.

Objective·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus(SLE)and other autoimmune diseases based on laboratory indications,and to evaluate its efficacy.Methods·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group,and 535 patients with other autoimmune diseases during the same period were selected as control group.Basic information and laboratory test indicators of the SLE group and control group were collected and compared.The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3,respectively.LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE.The nomogram for differential diagnosis of early SLE(SLE nomogram)was established according to the selected main risk factors.Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram.The receiver operator characteristic curve(ROC curve)and decision curve analysis(DCA)were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram,respectively.The"DynNom"package of R language was used to convert the nomogram into an electronic calculator,and its consistency with SLE nomogram was verified by data from 3 groups of patients.Results·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE,including antinuclear antibody(ANA),anti-double-stranded DNA(anti-dsDNA)antibody,anti-ribonucleoprotein antibody/anti-Simth antibody(anti-nRNP/Sm),anti-ribosomal P protein(anti-P)antibody,anti-nucleosome antibody(ANuA)and urinary protein(PRO),which were used to construct the SLE nomogram.The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set,respectively,and its area under the curve(AUC)was 0.889 and 0.869,respectively.The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95,the model achieved more net benefit.The prediction results of the electronic calculator showed that when ANA(titer 1∶100)was positive in SLE patient No.1,the prevalence was 0.166;when both ANA(titer 1∶100)and ANuA(titer 1∶100)were positive in patient No.2,the prevalence was 0.676;when all of PRO,ANA(titer 1∶100),ANuA(titer 1∶100)and anti-P antibody(titer 1∶100)were positive in patient No.3,the prevalence was 0.990,which was consistent with the differential diagnosis results of the SLE nomogram.Conclusion·The established SLE nomogram based on ANA,anti-dsDNA antibody,anti-nRNP/Sm,anti-P antibody,ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases,and have important clinical application value.

Objective To explore the intestinal barrier regulation effect of Butuyajie recipe on antibiotic-associated diarrhea rats.Methods 60 SD male rats were randomly divided into blank group,model group,positive drug group(1 g·kg-1),and high-dose,medium-dose and low-dose groups of Butuyajie recipe(40.5,20.25,10.125 g·kg-1).The model was replicated by intragastric administration of lincomycin hydrochloride(5 g·kg-1)for 7 consecutive days.After successful modeling,the materials were obtained after drug intervention for 7 days.Intestinal pathological morphology was observed by HE staining.ELISA kit to detect DAO,MPO,LPS.Take each organ tissue to detect bacterial translocation.Feces were collected for 16S rRNA gene high-throughput sequencing analysis.Results Compared with the normal group,the serum levels of DAO,MPO and LPS in the model group were significantly increased(P<0.001,P<0.01),and the sIgA content in the intestinal mucosa was significantly decreased(P<0.001).Promote intestinal bacterial translocation(P<0.001,P<0.01).The diversity of intestinal flora was significantly reduced,and the levels of intestinal microflora and genera were significantly changed.Butuyajie recipe can reduce the content of DAO,MPO and LPS(P<0.001,P<0.01,P<0.05),significantly increase the content of sIgA(P<0.01,P<0.05),and effectively inhibit the translocation of intestinal bacteria(P<0.001,P<0.01,P<0.05).At the same time,it corrects the intestinal microecological structure by increasing Firmicutes,inhibiting the proportion of Bacteroidetes and Proteobacteria,and regulating Lactobacillus,Sphingomonas,Pseudomonas,and Enterobacter.Conclusion Butuyajie recipe can reduce the permeability of intestinal mucosa,reduce the translocation of intestinal flora,protect the intestinal immune barrier,regulate the diversity of intestinal flora structure,improve the intestinal microecological disorder,and can effectively treat antibiotic-associated diarrhea.

Objective In order to explore the preventive effect and potential mechanism of Dai medicine Shenyeshan leech on chronic renal failure(CRF).The rat model of chronic renal failure was induced and replicated by adenine,and the pharmacodynamics and mechanism of CRF prevention and treatment were discussed.Methods SD rats were randomly divided into normal group,model group,Yougui pill group,high-dose alcohol extract group,middle-dose group,low-dose group.Prophylactic administration was performed 5 days before modeling,and starting from the 6th day,rats in the model group and each administration group were given 1.0%adenine by gavage in the morning,and drug treatment was given in the afternoon for 15 days.24 hours after the last administration,urine specific gravity(SG)was determined by refraction method;urine creatinine(Ucr)and 24-hour proteinuria(PRO)were determined by biochemical analyzer;red blood cell count(RBC),platelet number(Plt)were determined by cell analyzer,hemoglobin(HGB),mean platelet volume(Mpv),mean corpuscular volume(Mcv).Enzyme-linked immunosorbent assay kits were used to determine blood urea nitrogen(BUN),serum creatinine(Scr)content and urinary α1-microglobulin(α1-MG),kidney injury molecule-1(KIM-1)expression.Hematoxylin-eosin staining was used to observe the pathological morphology of rat kidneys,and immunohistochemical staining was used to analyze the expression of aquaporin 2(AQP2),transforming growth factor-β1(TGF-β1),and hypoxia-inducible factor(HIF-1α)-related proteins.Results Compared with the model group,the rats were significantly improved in various symptoms such as lethargy,sluggish reaction,yellow and rough coat with falling off,and the pathological morphology of the kidneys after administration.Blood routine indexes RBC,HGB,Mpv,Mcv levels increased,Plt level decreased.The 24-hour total urine volume decreased significantly(P<0.05),and the SG in the low-dose group increased significantly(P<0.05).When URO=3.2 μmol·L-1,urinary PRO could be recovered to negative after drug treatment.The levels of renal function injury indexes BUN,α1-MG and KIM-1 were significantly decreased(P<0.05,P<0.01,P<0.001);the renal index and Ccr levels of the rats in the administration group were significantly improved(P<0.05,P<0.01).At the same time,the related AQP2,TGF-β1 and HIF-1α protein expressions were improved.To sum up,it can be seen that the leech of the kidney leaf mountain can improve the renal histopathology and various indicators of chronic renal failure rats,reduce the degree of renal injury and renal fibrosis,and has a positive effect on the prevention and treatment of CRF in rats.

Objective To explore the effect and possible mechanism of petroleum ether extract from Gastrodia elata on A amyloid β-protein deposition in Caenorhabditis elegans(C.elegans).Methods C.elegans was used as the model organism,and the experiment was divided into blank group(Control group),GEPEE 0.5 mg·mL-1 group and GEPEE 1 mg·mL-1 group.The effects of GEPEE on paralysis,life span,oxidative stress,heat stress,reactive oxygen species(ROS)level and Aβ aggregation of C.elegans were investigated,qRT-PCR was used to detect the changes of gene expression related to insulin/IGF-1 signaling pathway(IIS)in C.elegans.The main components were analyzed by high performance liquid chromatography(HPLC).Results Compared with Control group,GEPEE could significantly improve the paralysis phenotype of C.elegans(P<0.01),prolong the lifespan of C.elegans(P<0.01),enhance the motility of C.elegans(P<0.01),and increased the resistance to external oxidative stress(P<0.01),the stress ability of high temperature(P<0.01),improved the deposition of Aβ in vivo(P<0.01),decreased the ROS content in C.elegans(P<0.01),decreased the expression levels of Aβ and DAF-2(P<0.01),increased the expression levels of DAF-16 and its target genes SOD-3,GSH-Px,HSF-1 and its target gene HSP-16.2,SKN-1 and its target gene GST-4(P<0.01).Its main components were p-hydroxybenzyl alcohol and p-ethoxylbenzyl alcohol by HPLC.This study showed that GEPEE can reduce Aβ-induced toxicity in CL4176 C.elegans by reducing ROS level in vivo,increasing antioxidant level and regulating IIS pathway.Conclusion GEPEE can inhibit the toxicity of Aβ protein,and its mechanism is related to the regulation of IIS signaling pathway.

Objective: To describe the CT features and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19).Method: A total of 9 COVID-19 infected pediatric patients were included in this study.Clinical history,laboratory examination,and detailed CT imaging features were analyzed.All patients underwent the first CT scanning on the same day of being diagnosed by realtime reverse-transcription polymerase chain reaction (rRT-PCR).A low-dose CT scan was performed during follow-up.Results: All the child patients had positive results.Four patients had cough and one patient had fever.One patient presented both cough and fever.Two children presented other symptoms like sore throat and stuffy nose.One child showed no clinical symptom.Five patients had positive initial CT findings with subtle lesions like ground-glass opacity (GGO) or spot-like mixed consolidation.Three patients were reported with negative results in the initial and follow-up CT examination.One patient was reported with initial negative CT findings but turning positive during the first follow-up.All patients had absorbed lesions on follow-up CT images after treatment.Conclusion: Pediatric COVID-19 patients have certain imaging and clinical features as well as disease prognosis.Children with COVID-19 tend to have normal or subtle CT findings and relatively better outcome.

Objective:To investigate the phenotype, genotype and clinical course of centronuclear myopathy(CNM) in children.Methods:Clinical data of patients with CNM in the Department of Pediatrics, Peking University First Hospital from October 2008 to December 2018 were collected.The clinical, pathological and genetic data of 9 children with CNM were retrospectively analyzed.The patients were followed up from 8 months to 8.6 years [(4.4±3.1) years].Results:(1)Clinical phenotype: there were 6 males and 3 females with onset age ranging from 1 d to 10 years.Generalized muscle weakness or motor retardation was the main complaint in 8 cases, while elevated muscle enzymes presented in 1 case.Varying degrees of skeletal muscle weakness were noted on examination in all patients, with facial muscle involvement in 4 cases.Six patients were followed up.No deterioration in motor function was noted, while 2 patients had improvement.There was no significant cardiac involvement in all 6 patients.Scoliosis occurred in 4 patients.Restrictive ventilator disorder developed in 2 out of the 5 patients who underwent pulmonary function tests.(2)Genotype: 8 out of 9 patients underwent gene test, confirmed gene diagnosis in 4 patients including: DNM2 gene (c.1856C>T, c.1893+ 1G>A was novel) de novo heterozygous mutation in 2 cases, RYR1 gene (c.2044C>G, c.6823G>A, both were novel) compound heterozygous mutation in 1 case, and TTN gene (c.107377+ 1G>A, c.2106_2107 insAAGCTGTA was novel) compound heterozygous mutation in 1 case. Conclusions:The course of centronuclear myopathy is relatively static, with more frequent involvement of facial muscles than myocardium.This study enriched the gene mutation spectrum of centronuclear myopathy (4 novel mutations).

OBJECTIVE: To design and synthesize phenylpyridine substituted semicarbazides and investigate their in vitro antitumor activities. METHODS: The target compounds were synthesized from acetophenone through condensation, cyclization,hydrazinolysis and reaction with isocyanates. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by MTT assay. RESULTS Sixteen novel compounds were obtained, and their structures were characterized by 1H-NMR, 13C-NMR and HRMS. In vitro bioassay indicated that most compounds had a certain degree of antitumor activity. Compound 51 displayed the most potential anticancer activity against these cancer cell lines with IC50 value of 9.15, 10.45 and 12.50 μmol·L-1, respectively. CONCLUSION: The series of compounds show preferable antitumor activities, which are worthy of further study.