[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Objective:To analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.

Background::In East Asia, Helicobacter pylori ( H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. Methods::We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. Results::We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns. Conclusions::H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. Registration::PROSPERO, No. CRD42023402510.

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

Objective:To assess the feasibility and effectiveness of transnasal ultra-thin gastrointestinal endoscope-guided ileus tube insertion for the treatment of adhesive intestinal obstruction in the elderly.Methods:Randomized controlled trial, a total of 81 elderly patients with adhesive intestinal obstruction were enrolled, with 46 receiving transnasal ultra-thin gastroscope-assisted tube placement(observation group)and 35 receiving conventional transoral gastroscope-assisted tube placement(control group). Tube insertion was carried out.Data on the time needed for tube placement, incidents of oral or nasal bleeding, rates of successful tube placement, physical signs of symptom relief and imaging signs of symptom relief were recorded and compared between the two groups.Results:The symptom remission rate within 3 d was 93.5%(43/46)in the observation group and 88.6%(31/35)in the control group, and the rate for imaging signs of symptom remission was 82.6%(38/46)in the observation group and 74.3%(26/35)in the control group.The differences in symptom remission and imaging signs of symptom remission within 3 d were not statistically significant between the two groups( χ2=0.144, 0.830, all P>0.05). In the observation group, the time needed for tube placement was(15.4±4.2)min, which was significantly shorter than that in the control group(21.3±3.1)min( t=6.984, P<0.01). The rate of successful tube placement was 100% in both groups.In terms of adverse reactions, the observation group had 1 patient with nasal bleeding, 2 with nausea and vomiting, and 1 with a sore throat, with an overall adverse reaction rate of 8.7%(4/46), while the control group had no patient with bleeding, 18 with nausea and vomiting, and 4 with a sore throat, with an overall adverse reaction rate of 62.9%(22/35). There was no statistically significant difference in nasal bleeding(Fisher's exact probability P=0.568)or a sore throat( χ2=1.559, P=0.212), but the differences in the incidence of nausea and vomiting as well as the incidence of total adverse reactions were statistically significant( χ2=23.694, 26.752, both P<0.01)between the two groups. Conclusions:Transnasal ultra-thin gastroscope-assisted tube placement can reduce discomfort such as nausea and vomiting during tube placement, the time needed for the procedure is short with a high success rate, and therefore has very good clinical value, especially for elderly patients.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Objective:To explore the efficacy and safety of in-class transition from proteasome inhibitor bortezomib to ixazomib in the treatment of newly-treated patients with multiple myeloma (MM).Methods:The clinical data of 63 newly-treated MM patients in Shenzhen Second People's Hospital from January 2018 to December 2020 were retrospectively analyzed. They were divided into transition group (23 cases) and bortezomib group (40 cases). Both groups were treated with bortezomib-containing regimen as the first-line treatment regimen. In case of intolerable adverse reactions, patients in the transition group were treated with ixazomib instead of bortezomib, while the patients in the bortezomib group did not undergo drug transition. The curative effect and progression-free survival (PFS) were compared between the two groups.Results:In the transition group, the overall response rate (ORR) before in-class transition was 95.7% (22/23), the rate of ≥ very good partial remission (VGPR) was 52.2% (12/23); the ORR after transition was 95.7% (22/23), and the rate of ≥ VGPR was 82.6% (19/23). In the bortezomib group, ORR was 90.0% (36/40), and the rate of ≥ VGPR was 72.5% (29/40). There was no significant difference in ORR and the rate of ≥VGPR between the two groups ( χ2 = 0.64, P=0.424; χ2 = 0.82, P = 0.364). The median number of cycles of PI therapy in the transition group was 9, and the median PFS time was not reached. The median number of cycles of PI therapy in the bortezomib group was 7.5, and the median PFS time was 30.0 months (95% CI 19.1-40.9 months), there was no significant difference in PFS between the two groups ( P = 0.275). In the bortezomib group, 12 patients discontinued bortezomib due to adverse reactions, the median PFS time was 20.0 months (95% CI 12.6-27.4 months), and the PFS of patients who discontinued PI in the transition group and the bortezomib group was compared, the difference was statistically significant ( P = 0.043). In the transition group, 21 patients (21/23, 91.3%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 13.0% (3/23); in the bortezomib group, 22 patients (22/40, 55.0%) developed peripheral neuropathy, and the incidence of ≥grade 3 adverse reactions was 12.5% (5/40). Conclusions:For newly-treated MM patients, the transition from bortezomib to ixazomib can improve the depth of remission and reduce the recurrence caused by the discontinuation of PI.

Objective:To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors.Methods:Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out.Results:The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months.Conclusion:HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.