Liver cancer is a prevalent and highly malignant cancer worldwide,with 90％of cases being hepatocellular carcinoma,presenting a significant risk to human health.As early-stage liver cancer often lacks specific manifestations,most patients with liver cancer are already in the middle and late stage of the disease when liver cancer is diagnosed,thus,missing the opportunity for optimal radical treatment.However,the exploration of the treatment for middle and advanced primary hepatocellular carcinoma has never ceased.In recent years,transarterial chemoembolization(TACE)has been included in the standard treatment regimens for primary hepatocellular carcinoma.With the advancement of multidisciplinary comprehensive treatment,various treatment options to reduce the burden of liver cancer lesion with satisfactory therapeutic results have been reported and have been widely used in clinical practice,e.g.hepatic artery infusion chemotherapy(HAIC),targeted therapy,and immunotherapy in combination with TACE,which have significantly improved the overall survival of patients with liver cancer.This paper aims to make a comprehensive review about the latest progress of combination use of TACE and other therapies in reducing tumor burden and improving patient survival in the treatment of primary hepatocellular carcinoma,and to summarize the key issues in combination therapy that require more in-depth research.(J Intervent Radiol,2024,33:688-692)

ObjectiveTo study the potential quality marker （Q-marker） of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， multivariate statistical analysis （MSA）， and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were employed to screen out the main marker components that caused differences between groups. Moreover， network pharmacology technology was applied to predict the potential "sore throat-relieving" components， and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds， including alkaloids， diterpenoid lactones， and sterols， were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA： Columbamine， jatrorrhizine， palmatine， menisperine， and columbin. Network pharmacology analysis yielded six compounds： tetrahydropalmatine， palmatine， menisperine， fibleucin， neoechinulin A， and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6， epidermal growth factor receptor， prostaglandin G/H synthase 2， matrix metalloproteinase-9， proto-oncogene tyrosine-protein kinase Src and other targets， and regulating Hepatitis B， influenza A， human T-cell virus infection， human cytomegalovirus infection， coronavirus disease-2019， and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine， menisperine， and columbin， which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix， which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

Objective:To explore the relationship between urinary exosomal microRNA (exo-miR) - 155 in patients with type 2 diabetes mellitus (T2DM) and the onset and severity of diabetic kidney disease (DKD).Methods:From January to May 2019, 5 patients with T2DM normoalbuminuria and 5 patients with type 2 DKD were recruited from the Department of Endocrinology and Metabolism of Chongming Hospital of Shanghai Health Medical College as a microRNA screening cohort. Urine samples were collected to extract urinary exosomes, and the urine exo-miR spectrum was detected and analyzed using the miRCURY LNA array. From June 2019 to October 2022, 351 patients with T2DM who met the enrollment criteria and were matched by age and sex were included in the validation cohort in the Department of Endocrinology and Metabolism of the hospital. Patients were divided into 3 groups according to urinary albumin/creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=143), microalbuminuria group (30 mg/g≤UACR≤300 mg/g, n=171) and macroalbuminuria group (UACR>300 mg/g, n=37). According to DKD diagnostic guidelines, microalbuminuria group and macroalbuminuria group were classified into DKD group. Real-time fluorescence quantitative PCR was used to detect the expression level of exo-miR-155 in urine. Results:The results of transmission electron microscopy, nanoparticle tracking analysis, and Western blotting showed that the extraction of exosome vesicles was successful. In the screening cohort, according to the screening criteria of P<0.05 and fold changes (FC)>1.5, 226 differentially expressed miRNAs were identified from the urinary exosomes of the DKD group compared to the T2DM group. Among them, miR-155 ranged highest (FC=32.75, P<0.001). In the validation cohort, compared with the normoalbuminuria group [0.76 (0.55, 0.95)], the macroalbuminuria group [1.84 (1.18, 2.42)] had the most significant increase in urinary exo-miR-155 level ( Z=-7.411, P<0.001), followed by the microalbuminuria group [0.86 (0.69, 1.25)] ( Z=-4.092, P<0.001), and the urinary exo-miR-155 level in the macroalbuminuria group was significantly higher than that in the microalbuminuria group ( Z=-5.841, P<0.001). The correlation analysis showed that urinary exo-miR-155 level was positively correlated with UACR ( r s=0.329, P<0.001) and negatively correlated with estimated glomerular filtration rate ( r s=-0.249, P=0.015). The results of receiver operating characteristic curve analysis showed that the area under the curve of urinary exo-miR-155 level predicted DKD progression in T2DM patients was 0.892 (95% CI 0.859-0.925), corresponding cutoff value was 0.982, and the sensitivity and specificity were 71.9% and 87.7%, respectively. Multivariate logistic regression analysis showed that urinary exo-miR-155≥0.982 was an independent risk factor for progression to DKD in T2DM patients ( OR=3.310, 95% CI 1.981-5.530, P<0.001). Conclusion:The expression level of urinary exo-miR-155 is increased in T2DM patients with microalbuminuria and macroalbuminuria, which is related to the degree of albuminuria, and can be used as a predictive marker to identify potential DKD.

The online version of the original article can be found at https://doi.org/10.1631/jzus.B2000190 Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2020 21(10):779-795 https://doi.org/10.1631/jzus.B2000190.

OBJECTIVE：To study the improvement effect and mechanism of MEBO on lipopolysaccharide （LPS）-induced injury of rat skin fibroblasts. METHODS ：Skin fibroblasts of rats were divided into control group ，LPS group （5 μg/mL）， Kangfuxin solution group （positive control ，5 μg/mL LPS+1.25％ Kangfuxin solution ）and MEBO group （5 μg/mL LPS+0.6 mg/mL MEBO），with 6 wells in each group. Inflammatory injury cell model was induced by LPS （except for control group ）. After a certain period of cultivation ，the cell survival rate and cell migration rate were detected in each group. The contents of TNF-α and IL-6 in cell supernatant was detected. The localization and fluorescence intensity of IL- 6 protein were detected. The protein expression of PTEN ，p-p65，TNF-α，IL-6，PI3K and Akt in the fibroblasts were also determined. RESULTS ：Compared with control group ，survival rate of the fibroblasts was increased significantly in LPS group ，while cell migration was decreased significantly；the contents of TNF-α and IL-6 in cell supernatant as well as relative protein expression of PTEN ，p-p65，TNF-α， IL-6 and PI 3K were increased significantly （P＜0.05 or P＜0.01）；IL-6 protein mainly expressed in the cytoplasm ，and the fluorescence intensity was enhanced. Compared with LPS group ，survival rate of the fibroblasts was decreased significantly in Kangfuxin solution group and MEBO group ，while migration rate was increased significantly ；the contents of TNF-α and IL-6， relative protein expression of PTEN ，p-p65，TNF-α，IL-6（except for Kangfuxin solution group ），PI3K and Akt （except for Kangfuxin solution group ） were decreased significantly （P＜0.05 or P＜0.01），while fluorescence intensity of IL- 6 protein decreased；relative protein expression of TNF-α，IL-6，PI3K and Akt in MEBO group were significantly lower than Kangfuxin solution group （P＜0.05 or P＜0.01）. CONCLUSIONS ：MEBO can inhibit the proliferation of LPS-induced skin fibroblasts ， reduce the level of inflammatory factors and the intensity of inflammatory reaction ， which may be related to the jiang- down-regulation of PTEN/NF-κB，PI3K/Akt signaling pathway.

Based on the transcriptome analysis data of a Bacillus licheniformis, a novel bidirectional promoter was identified from the strain and its transcriptional strength was analyzed. The expression level of a Bacillus clausii derived alkaline protease gene driven by the bidirectional promoter was studied by using the known strong constitutive promoter pShuttle-09 as a control. Three recombinant expression vectors and the corresponding recombinant bacteria were constructed. Under the control of the new promoter pLA and its reverse promoter pLB, the alkaline protease expression level respectively reached 164 U/mL and 111 U/mL. The results indicated that the transcription strength of pLA was significantly higher than that of pShuttle-09 and pLB, and both the pLA and pLB promoters could initiate the expression of the alkaline protease. Thus, it provides a new expression element for the heterogenous genes in Bacillus sp. and a new idea for the co-expression of two genes in one prokaryotic strain.
Bacillus subtilis ; Promoter Regions, Genetic

Cyclophilin A (CypA) is found to be highly expressed in different kinds of tumor cells,which could regulate the occurrence and development of many kinds of tumor through multiple signal transduction pathways such as inducing the formation of inflammatory carcinoma,accelerating the transcription cycle of tumor cells,promoting the invasion and metastasis of tumor cells,inhibiting the apoptosis of tumor cells and reducing the sensitivity of tumor cells to chemotherapy drugs.It suggests that CypA might be considered as a kind of oncogene,which is expected to be a novel target for tumor treatment.

Objective To investigate the clinical,pathological and gene mutation features of infantile systemic hyalinosis (ISH).Method Data of a child with ISH seen in Haikou Hospital were retrospectively analyzed for the diagnosis and differential diagnosis of infantile systemic hyalinosis and the relevant reports in literature were reviewed.Result A 1 year and 1 month old boy showed limbs joint stiffness,limited mobility and double knee flexion at his first month of life.At third month,red rashes appeared on the body and gradually became purple,most of them were seen on the back and they were higher than the skin surface,uneven and did not fade when pressed.Undergoing X-ray the boy showed double knee varus deformity.Histopathological examination of the neck skin lesions proved hyalinosis.The gene examination revealed ANTXR2 exon 13,c.1073 delC/c.1074 delT mutations,which were hot spots mutation of ISH,then the diagnosis of ISH was confirmed.Using " Infantile systemic hyalinosis" as a keyword,literature in Wanfang network,PubMed and China National Knowledge Infrastructure from 1978 to 2015 was searched,we found 48 foreign cases,one Chinese Taiwan case.All the cases had joint contractures.Short stature and skin lesions with hyperpigmentation in 40 cases,gingival hyperplasia in 36 cases,perianal nodules in 32 cases,skin thickening in 31 cases,osteoporosis in 30 cases,recurrent diarrhea in 30 cases,repeated infections in 25 cases;49 cases were reported as autosomal recessive genetic disease,of whom 18 cases underwent genetic testing,the pathogenic gene was located in the fourth chromosome q21 position,the gene was encoded as capillary morphogenesis Protein 2 (CMG2),also known as anthrax toxin receptor 2 (ANTXR2),but there were various mutation spots in the gene.Among the 18 cases,9 were of frameshift,8 of missense and 1 of splice defect.Onset ages were mainly within 4 months after birth.Without special treatment most patients died at about 2 years of age due to repeated infections.Conclusion ISH is a rare disease,which occurs at early age.ISH has special clinical features:joint contracture and limited mobility,special skin rash and pigmentation,skin hyaline degeneration of pathological examination.ISH is an autosomal recessive genetic disease with mutation gene located in the fourth chromosome q21 position.Currently there is no effective treatment for ISH,with which patients are prone to die of recurrent infections.

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) μm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

A 36-year-old female presented with multiple dark brown papules on the chest and abdomen for more than 10 years,which had gradually increased in number.Physical examination revealed dozens of dark brown,flat papules measuring 1-3 mm in diameter in the chest and abdomen.Most of the lesions had a smooth surface,and some lesions gave a papilloma-like appearance,with no confluent trend.Biopsy of abdominal lesions showed mild hyperkeratosis of epidermis,acanthosis,extension of epidermal protrusions forming a reticulated appearance,horn pseudocysts in prickle cell layer,enhanced pigmentation of basal layer,and a sparse lymphocytic perivascular infiltrate in superficial dermis.A diagnosis of dermatosis papulosa nigra (DPN) was made.