1.Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy.
Chao CHEN ; Shiyu DU ; Qianglan LU ; Xueting SHEN ; Shuai DING ; Lihua QU ; Yamei GAO ; Zhiqiang YIN ; Zhe LI ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2025;15(10):5431-5443
Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C2P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn2+ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C2P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.
2.Application of endoscopic retrograde cholangiopancreatography in elderly patients
Yongkang TAO ; Shiyu DU ; Long FANG
Chinese Journal of Geriatrics 2025;44(6):740-744
This article reviews the use of endoscopic retrograde cholangiopancreatography(ERCP)in elderly patients.ERCP is widely used in elderly patients with pancreaticobiliary diseases, with a high success rate.It is mainly used for the diagnosis and treatment of biliary calculi, benign and malignant biliary strictures, acute pancreatitis, chronic pancreatitis, and pancreatic tumors and other disease.ERCP plays an important role in accurate diagnosis and treatment, such as the removal of biliary calculi and the placement of stents for biliary obstruction.The perioperative management of ERCP in elderly patients includes preoperative assessment(medical history, nutrition, comorbidities, medication, psychology, etc.), intraoperative considerations(cannulation, stone removal, stent placement, etc.)and postoperative diet and nutrition management.Common complications include anesthesia-related risks and cardiopulmonary complications, postoperative pancreatitis, bleeding, perforation, and infection, which require corresponding measures need to be taken for prevention and treatment.ERCP plays an important role in the diagnosis and treatment of elderly patients, but faces many challenges.Comprehensive perioperative management can reduce risks.With the development of technology, its application prospects are broad, and it is expected to improve the treatment effect and quality of life of elderly patients.
3.Analysis of clinical features of elderly patients with gastroesophageal reflux disease and extraesophageal symptoms
Huifen WANG ; Miao WANG ; Shiyu DU ; Yanli ZHANG
Chinese Journal of Geriatrics 2025;44(6):776-781
Objective:To compare clinical features, esophageal motility, and reflux characteristics in elderly patients with gastroesophageal reflux disease(GERD)with and without extraesophageal symptoms.Methods:This study was conducted as a cross-sectional analysis involving 75 patients aged 60 years and older, who visited the outpatient department of gastroenterology at China-Japan Friendship Hospital between January and December 2023.Among these, 43 patients exhibited extraesophageal symptoms [23 males, 20 females; median age 69(66, 75)], while 32 patients did not present with such symptoms [12 males, 20 females; median age 69(66, 73.75)].We collected data regarding the patients' demographic characteristics, lifestyle habits, and comorbidities via a questionnaire, and analyzed the range of extraesophageal symptoms.The presence of reflux esophagitis was assessed according to the Los Angeles classification, and the status of the gastroesophageal valve was evaluated through gastroscopy.Additionally, we measured esophageal motility and reflux characteristics using high-resolution manometry and 24-hour pH-impedance monitoring.Results:The smoking rate was significantly higher in patients with extraesophageal symptoms compared to those without extraesophageal symptoms[39.53%(17/43) vs.15.63%(5/32), P=0.039].Conversely, the prevalence of hypertension was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[41.86%(18/43) vs.65.63%(21/32), χ2=4.151, P=0.042].Among patients with extraesophageal symptoms, the proportion experiencing pharyngeal symptoms was the highest at 83.72% (36/43), followed by oral symptoms at 32.56%(14/43), while the lowest proportion was for respiratory symptoms at 16.28%(7/43).The esophageal body peristaltic contraction rate was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[100%(100%, 100%) vs.100%(80%, 100%), Z=-2.671, P=0.008].The number of non-acid reflux episodes was significantly higher in patients with extraesophageal symptoms compared to those without[5.00(1.00, 5.00) vs.1.00(1.00, 2.00), Z=-3.842, P<0.001].Additionally, the proportion of proximal reflux was significantly higher in patients with extraesophageal symptoms compared to those without[83.8%(65.6%, 95.4%) vs.68.5%(59.8%, 77.35%), Z=-2.037, P=0.042]. Conclusions:Patients with GERD and extraesophageal symptoms exhibit a higher prevalence of smoking, diminished peristaltic function in the esophageal body, an increased incidence of proximal esophageal reflux, and a greater number of non-acid reflux episodes.
4.Construction of a value evaluation index system for health management and logistics positions in public hospitals
Zhao LONG ; Chunping LI ; Qiwen XIAO ; Lan LI ; Yuan ZHOU ; Shiyu YANG ; CIREN SUOLANG ; Jiangbo DU ; YANGZONG DAWA ; Lingli DING
Modern Hospital 2025;25(2):234-237,242
Objective To develop a value evaluation index system for health management and logistics positions in pub-lic hospitals,providing a research tool for future performance evaluations and salary reform.Methods Literature review,focus group interviews,and the point-factor method were employed to establish an initial index pool.A public hospital in Guangzhou was selected as a case study.Delphi expert consultation was then utilized to refine and finalize the indicators for the evaluation system.Results For the two rounds of Delphi expert consultation,the response rates were 87.5%and 100.0%,with the expert authority coefficient of 0.812.The Kendall's W coordination coefficients were 0.796 and 0.624 for the first round,and 0.747 and 0.918 for the second,(all<0.001).The coefficients of variation ranged from 0.157 to 0.265 for the first round and from 0.108 to 0.230 for the second round.Experts provided four suggestions,leading to the removal of one secondary indicator and modifications to the definitions of three others.Finally,the evaluation system consists of 4 primary indicators and 12 secondary indicators.Conclusion This system can provide a research tool and reference for the follow-up performance evaluation,improve the salary reform of public hospitals,and promote the high-quality development of public hospitals.
5.Construction of a value evaluation index system for health management and logistics positions in public hospitals
Zhao LONG ; Chunping LI ; Qiwen XIAO ; Lan LI ; Yuan ZHOU ; Shiyu YANG ; CIREN SUOLANG ; Jiangbo DU ; YANGZONG DAWA ; Lingli DING
Modern Hospital 2025;25(2):234-237,242
Objective To develop a value evaluation index system for health management and logistics positions in pub-lic hospitals,providing a research tool for future performance evaluations and salary reform.Methods Literature review,focus group interviews,and the point-factor method were employed to establish an initial index pool.A public hospital in Guangzhou was selected as a case study.Delphi expert consultation was then utilized to refine and finalize the indicators for the evaluation system.Results For the two rounds of Delphi expert consultation,the response rates were 87.5%and 100.0%,with the expert authority coefficient of 0.812.The Kendall's W coordination coefficients were 0.796 and 0.624 for the first round,and 0.747 and 0.918 for the second,(all<0.001).The coefficients of variation ranged from 0.157 to 0.265 for the first round and from 0.108 to 0.230 for the second round.Experts provided four suggestions,leading to the removal of one secondary indicator and modifications to the definitions of three others.Finally,the evaluation system consists of 4 primary indicators and 12 secondary indicators.Conclusion This system can provide a research tool and reference for the follow-up performance evaluation,improve the salary reform of public hospitals,and promote the high-quality development of public hospitals.
6.Application of endoscopic retrograde cholangiopancreatography in elderly patients
Yongkang TAO ; Shiyu DU ; Long FANG
Chinese Journal of Geriatrics 2025;44(6):740-744
This article reviews the use of endoscopic retrograde cholangiopancreatography(ERCP)in elderly patients.ERCP is widely used in elderly patients with pancreaticobiliary diseases, with a high success rate.It is mainly used for the diagnosis and treatment of biliary calculi, benign and malignant biliary strictures, acute pancreatitis, chronic pancreatitis, and pancreatic tumors and other disease.ERCP plays an important role in accurate diagnosis and treatment, such as the removal of biliary calculi and the placement of stents for biliary obstruction.The perioperative management of ERCP in elderly patients includes preoperative assessment(medical history, nutrition, comorbidities, medication, psychology, etc.), intraoperative considerations(cannulation, stone removal, stent placement, etc.)and postoperative diet and nutrition management.Common complications include anesthesia-related risks and cardiopulmonary complications, postoperative pancreatitis, bleeding, perforation, and infection, which require corresponding measures need to be taken for prevention and treatment.ERCP plays an important role in the diagnosis and treatment of elderly patients, but faces many challenges.Comprehensive perioperative management can reduce risks.With the development of technology, its application prospects are broad, and it is expected to improve the treatment effect and quality of life of elderly patients.
7.Analysis of clinical features of elderly patients with gastroesophageal reflux disease and extraesophageal symptoms
Huifen WANG ; Miao WANG ; Shiyu DU ; Yanli ZHANG
Chinese Journal of Geriatrics 2025;44(6):776-781
Objective:To compare clinical features, esophageal motility, and reflux characteristics in elderly patients with gastroesophageal reflux disease(GERD)with and without extraesophageal symptoms.Methods:This study was conducted as a cross-sectional analysis involving 75 patients aged 60 years and older, who visited the outpatient department of gastroenterology at China-Japan Friendship Hospital between January and December 2023.Among these, 43 patients exhibited extraesophageal symptoms [23 males, 20 females; median age 69(66, 75)], while 32 patients did not present with such symptoms [12 males, 20 females; median age 69(66, 73.75)].We collected data regarding the patients' demographic characteristics, lifestyle habits, and comorbidities via a questionnaire, and analyzed the range of extraesophageal symptoms.The presence of reflux esophagitis was assessed according to the Los Angeles classification, and the status of the gastroesophageal valve was evaluated through gastroscopy.Additionally, we measured esophageal motility and reflux characteristics using high-resolution manometry and 24-hour pH-impedance monitoring.Results:The smoking rate was significantly higher in patients with extraesophageal symptoms compared to those without extraesophageal symptoms[39.53%(17/43) vs.15.63%(5/32), P=0.039].Conversely, the prevalence of hypertension was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[41.86%(18/43) vs.65.63%(21/32), χ2=4.151, P=0.042].Among patients with extraesophageal symptoms, the proportion experiencing pharyngeal symptoms was the highest at 83.72% (36/43), followed by oral symptoms at 32.56%(14/43), while the lowest proportion was for respiratory symptoms at 16.28%(7/43).The esophageal body peristaltic contraction rate was significantly higher in patients without extraesophageal symptoms compared to those with extraesophageal symptoms[100%(100%, 100%) vs.100%(80%, 100%), Z=-2.671, P=0.008].The number of non-acid reflux episodes was significantly higher in patients with extraesophageal symptoms compared to those without[5.00(1.00, 5.00) vs.1.00(1.00, 2.00), Z=-3.842, P<0.001].Additionally, the proportion of proximal reflux was significantly higher in patients with extraesophageal symptoms compared to those without[83.8%(65.6%, 95.4%) vs.68.5%(59.8%, 77.35%), Z=-2.037, P=0.042]. Conclusions:Patients with GERD and extraesophageal symptoms exhibit a higher prevalence of smoking, diminished peristaltic function in the esophageal body, an increased incidence of proximal esophageal reflux, and a greater number of non-acid reflux episodes.
8.Clinical characteristics of primary malignant melanoma of esophagus in elderly Chinese patients
Yongkang TAO ; Long FANG ; Geng QIN ; Shuang ZHANG ; Xiangrong ZHANG ; Junhai ZHANG ; Shiyu DU
Chinese Journal of Geriatrics 2024;43(6):716-720
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.
9.Antibiotic resistance in Helicobacter pylori among children and adolescents in East Asia: A systematic review and meta-analysis
Yuhang ZHOU ; Yanli ZHANG ; Shiyu DU
Chinese Medical Journal 2024;137(16):1926-1938
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.
10.Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2024;14(2):897-899
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

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