Objective:To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed.Results:The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade Ⅳ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade Ⅲ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade Ⅰ-Ⅱ adverse reactions. There were no serious complications related to interventional surgery.Conclusions:Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Clinical data of a child with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) diagnosed in the First Affiliated Hospital of Zhengzhou University in June 2020 were retrospectively analyzed.A female patient with 1 year and 2 months old presented with 10 months of developmental delay and 1 month of recurrent seizures.Physical examinations showed grade Ⅲ muscle strength of limbs, slightly higher muscle tone, active reflex of bilateral knee tendons, normal reflex of bilateral achilles tendons, and positive Babinski sign.Brain magnetic resonance imaging (MRI) showed bilateral cerebral hemisphere atrophy and diffuse abnormal signals.The whole exome sequencing test showed two heterozygous mutations of the DARS2 gene in the present case.There are no reports of early-onset LBSL gene mutation in Chinese population.A total of 6 related foreign literatures have been reported.All affected cases present psychomotor development disorders and other encephalopathy manifestations.Brain MRI involvement and DARS2 gene mutations are found in previous reports.Therefore, for children with developmental retardation, epilepsy, and diffuse abnormal signals in both cerebral hemispheres examined by brain MRI, genetic testing is recommended to confirm the diagnosis, guide prenatal diagnosis and genetic counseling.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.

A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.

ObjectiveTo investigate the value of ABCR clinical scoring system in guiding repeated transcatheter arterial chemoembolization (TACE) therapy for patients with hepatocellular carcinoma (HCC) and the treatment strategies for patients with an ABCR score of 1-3. MethodsThe patients with HCC who underwent TACE in The First Affiliated Hospital of Soochow University from January 2008 to December 2017 were enrolled. In order to investigate the effect of repeated TACE in patients with different ABCR scores, 229 patients who underwent repeated TACE consecutively (at least twice, without systemic therapy) were enrolled as group A, which was further divided into group A1 with 92 patients (an ABCR score of ≤0), group A2 with 78 patients (an ABCR score of 1-3), and group A3 with 59 patients (an ABCR score of ≥4). In order to investigate the survival time of patients with an ABCR score of 1-3 who received different regimens after first TACE therapy, 118 patients with an ABCR score of 1-3 who received TACE for the first time were enrolled as group B, which was further divided into group B1 with 78 patients (treated with TACE after first TACE therapy), group B2 with 21 patients (treated with TACE combined with sorafenib), and group B3 with 19 patients (treated with sorafenib alone). The survival of the above groups of patients were analyzed. The Fisher’s exact test was used for comparison of categorical data between groups, the Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival time between groups. ResultsThe median survival time was 320 months (95% confidence interval ［CI］: 27.7-36.3) in group A1, 10.3 months (95%CI: 8.4-12.2) in group A2, and 4.6 months (95%CI: 3.7-5.5) in group A3. Group A1 had a better survival time than group A2 (χ2=106.99, P＜0.01), and group A2 had a better survival time than group A3 (χ2=49.66, P＜0.01). The median survival time was 10.3 months (95%CI: 8.4-12.2) in group B1, 14.8 months (95%CI: 7.8-21.8) in group B2, and 6.0 months (95%CI: 4.6-7.4) in group B3, and group B2 had a better survival time than group B1 (χ2=6.80, P＜0.01) and group B3 (χ2=29.89, P＜0.01). ConclusionThe ABCR score has a certain guiding significance for the treatment of HCC patients. Repeated TACE may be considered for patients with an ABCR score of ≤0, while patients with an ABCR score of ≥4 may not benefit from further TACE therapy, and TACE combined with sorafenib might bring maximum benefits to patients with an ABCR score of 1-3.

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

Objective To investigate the effect of exercise diary on arm exercise compliance ofpatients with peripherally inserted centralcatheter (PICC). Methods Thirty patients with PICC hospitalized in our hospital from June to August in 2017 were selected as the control group, where the patients received guidance on functional exercises through arm exercise videos and routine methods. Another thirty-two patients hospitalized in our hospital from September to November of 2017 were selected as the observation group, where in addition to the same treatment as in the control group and these patients received interventions using their self-designed exercise diary for a total of 31 days. Their compliance with functional exercises before and after intervention and the incidences of venous thrombosis after intervention were compared between the two groups. Results After interventions, the compliance rate of arm exercises in the observation group was significantly higher than that of the control group (90.6% vs. 26.7%, P＜0.05). The incidence of venous thrombosis in the observation group was significantly lower than that of the control group (3.1% vs. 30.0% , P＜0.05). Conclusions Exercise diary can improve the arm exercise compliance of PICC patients and prevent the occurrence of venous thrombosis. It is worthy of clinical application and promotion.