In recent years, with the clinical application of minimally invasive surgical techniques and comprehensive preoperative treatment, the survival rate of locally advanced esophageal cancer has significantly improved. However, the treatment of metastatic esophagogastric cancer still relies mainly on systemic therapy, and immunotherapy combined with chemotherapy has become a first-line treatment option, prolonging the survival of patients with metastatic esophageal cancer. Oligometastatic esophageal cancer is expected to bring survival benefits through systemic therapy combined with local treatment. The 2024 European clinical practice guidelines for oligometastatic esophagogastric cancer have been officially released, which standardize the definition, diagnosis, and treatment of oligometastatic esophageal cancer for further prospective studies. The authors interpret this guideline, especially by reviewing the clinical evidence of oligometastatic esophageal squamous cell carcinoma, to provide reference for the diagnosis and treatment of oligometastatic esophageal cancer in China.

The investigator-initiated trials （IIT）， as a widely existing form of clinical research both domestically and internationally， have attracted the attention of governments around the world due to the potential legal risks and issues they may cause， and the trend of legal supervision has gradually strengthened. The legal regulation of IIT in China is still in its early stages， with numerous legal issues that need to be clarified and sorted out. Based on the domestic and international legal reviews of IIT， this paper systematically sorted out the current situation of legal supervision of IIT in China and examined the existing issues， including weak legislative rules， incomplete regulatory systems， imperfect protection rules for research participants and informed consent systems， inadequate regulation of conflicts of interest management， and lax legal supervision of ethical review. Furthermore， this paper proposed suggestions for legal regulation of IIT from three perspectives， including strengthening legislation and emphasizing regulation， improving the mechanism for protecting research participants’ rights and interests， and balancing the legalization of IIT and the scientific development of clinical research， with a view to providing references for legal regulatory paths of IIT in China.

Objective To investigate the relationship between inflammation index and the severity of cere-bral small vessel disease.Methods A total of 168 patients with cerebral small vessel disease who were admit-ted to the Eighth People's Hospital of Hebei from August 2019 to October 2022 were selected as the study ob-jects.The study subjects were divided into cerebral small vessel disease with light burden(light burden group)and cerebral small vessel disease with medium-heavy burden(medium-heavy burden group)according to the total imaging burden score of cerebral small vessel disease.The basic data and systemic immune-inflam-matory index(SII),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and monocyte to lymphocyte ratio(MLR)were compared between the two groups.Spearman correlation analysis was used to evaluate the correlation between SII,NLR,PLR and MLR and the total imaging burden score of cerebral small vessel disease,and the influence of SII,NLR,PLR and MLR on the medium-heavy burden of cerebral small vessel disease was further analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of SII,NLR,PLR and MLR in the severity of cere-bral small vessel disease.Results The age,smoking history,hypertension history,neutrophil,platelet,SII,NLR,PLR and MLR in medium-heavy burden group were significantly higher than those in light burden group,and lymphocyte was significantly lower than that in light burden group,with statistical significance(P<0.05).Spearman correlation analysis showed that SII(r=0.377),NLR(r=0.516),PLR(r=0.486)and MLR(r=0.391)were positively correlated with the total imaging burden score of cerebral small vessel disease(P<0.001).Multivariate Logistic regression analysis showed that age,neutrophil,platelet,SII,NLR,PLR and MLR were independent risk factors for medium-heavy burden in cerebral small vessel disease,and lymphocyte was independent protective factor for medium-heavy burden in cerebral small vessel disease(P<0.05).ROC curve analysis results showed that the area under the curve of SII,NLR,PLR and MLR separately detected were 0.720(95%CI:0.646-0.787),0.802(95%CI:0.733-0.859),0.784(95%CI:0.714-0.843)and 0.728(95%CI:0.654-0.794),respectively.The area under the curve of the combined detection of the four indexes was higher than that of the single detection of each index(P<0.05).Conclusion The combined detection of SII,NLR,PLR and MLR has high predictive value for the severity of cerebral small vessel dis-ease,and is worthy of clinical promotion.

The aim of this study was to prepare a self-assembled nanoparticle monkeypox vaccine candidate and study its immune response characteristics,so as to provide reference test data for its vaccine design.The antigen protein A29L-SpyTag and the backbone protein Mi3-SpyCatcher were expressed and purified by prokaryotic system,and nanoparticles A29L-Mi3 were prepared by chemical assembly,then the antibody titers were determined by ELISA,the antibody neutralization was determined by plaque test,and the cytokine secretion of lymphocytes was determined by flow cytometry to describe the immune response characteristics.Data showed that A29L-Mi3 nanoparticles were successfully prepared,and the particles were uniformly distributed in hollow cages,with an average particle size of(29±0.19)nm.After the A29L-Mi3 nanoparticle vaccine candidate was combined with SP01 adjuvant,the neutralizing antibody titer was stronger than that of the A29L protein candidate,and the A29L-Mi3 nanoparticle vaccine candidate could obtain neutralizing antibodies with similar titers after two immunizations.The level of mouse T lymphocyte immune response activated by the A29L-Mi3 nanoparticle vaccine candidate was higher than that of the A29L protein vaccine candidate.In conclusion,A29L-Mi3 protein nanoparticles with uniform structure have successfully assembled in vitro,which has strong immunogenicity and improved neutralization ability after combination with SP01 adjuvant,thus provided reference data for the optimization of immune programs.In addition,the level of cellular immune response is higher than that of A29L protein alone,which provides a reference for the design and development of monkeypox vaccine.

Objective:To study the role of ML-SA5, an agonist of the lysosomal Ca 2+ channel transient receptor potential mucolipin 1 (TRPML1), in promoting lysosomal exocytosis to facilitate intracellular uranium removal and alleviate uranium-induced cellular damage for human renal proximal tubule epithelial cells (HK-2) exposed to uranyl acetate. Methods:HK-2 cells were divided into the following groups to be exposed to uranyl acetate at either 0 or 300 μmol/L for 24 h, followed by treatment with ML-SA5 and/or the lysosomal exocytosis inhibitor vacuolin-1 for 0.5 h: control group (Ctrl group), ML-SA5 group (M group), vacuolin-1 group (V group), ML-SA5 plus vacuolin-1 group (M+ V group), uranium exposure group (U group), uranium exposure plus ML-SA5 group (U+ M group), uranium exposure plus vacuolin-1 group (U+ V group), and uranium exposure plus ML-SA5 plus vacuolin-1 group (U+ M+ V group). We localized lysosome-associated membrane protein-1 (LAMP-1) on the plasma membrane (surface LAMP-1) by immunofluorescence assay; measured intracellular uranium content by inductively coupled plasma mass spectrometry; measured the level of kidney injury molecule-1 (KIM-1) by immunofluorescence assay; measured the rate of cell death with Calcein-AM/PI double staining; determined the subcellular localization of transcription factor EB (TFEB) and the levels of LAMP-1 and TRPML1 proteins by immunofluorescence assay; and measured the number of lysosomes using LysoTracker probes.Results:Compared with the Ctrl group, the U group showed significant increases in the surface LAMP-1 protein level ( t = 12.86, P < 0.05), KIM-1 protein level ( t = 18.86, P < 0.05), cell death rate ( t = 38.53, P < 0.05), TFEB nuclear translocation ( t = 9.12, P < 0.05), the protein expression levels of TFEB’s downstream target genes LAMP-1 ( t = 16.47, P < 0.05) and TRPML1 ( t = 32.33, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 7.75, P < 0.05). Compared with the U group, the U+ M group showed a significantly increased surface LAMP-1 level ( t = 3.33, P < 0.05) and significant decreases in the intracellular uranium level ( t = 5.01, P < 0.05), KIM-1 protein expression level ( t = 3.81, P < 0.05), and cell death rate ( t = 3.24, P < 0.05); all these effects in the U+ M group could be neutralized by the lysosomal exocytosis inhibitor vacuolin-1; and in addition, ML-SA5 significantly increased TFEB nuclear translocation ( t = 9.20, P < 0.05), the protein expression levels of LAMP-1 ( t = 3.05, P < 0.05) and TRPML1 ( t = 3.17, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 3.13, P < 0.05). Conclusions:The TRPML1 agonist ML-SA5 can promote lysosomal exocytosis to enhance intracellular uranium clearance and reduce uranium-induced cellular damage/death in uranium-loaded HK-2 cells, through activating TFEB to up-regulate lysosome biogenesis and TRPML1 protein expression.

Objective To analyze the impact of feedforward control nursing intervention on emergence agitation and recovery quality in general anesthesia surgery patients. Methods A total of 118 patients undergoing general anesthesia surgery were selected by convenient sampling, and randomly divided into control group and observation group, with 59 patients in each group. The control group received routine nursing intervention during emergence anesthesia, while the observation group received feedforward control nursing intervention. The incidence of emergence agitation, recovery quality, pain condition, and nursing quality were compared between the two groups. Results The incidence of emergence agitation during emergence in the observation group was significantly lower than that in the control group (42.37% versus 69.49%, P < 0.05). The Richmond Agitation-Sedation Scale (RASS) scores, duration and frequency of agitation were lower or shorter in the observation group than those in the control group (P < 0.05). The observation group exhibited shorter time for spontaneous respiration recovery, eye opening, extubation, full consciousness, and stay in the postanesthesia care unit compared to the control group(P < 0.05). The Steward emergence score was higher in the observation group (P < 0.05). The postoperative pain score was lower, while nursing quality score was higher in the observation group than those in the control group(P < 0.05). Conclusion Feedforward control nursing intervention can reduce the incidence of emergence agitation in general anesthesia surgery patients, improve recovery quality, alleviate postoperative pain, and enhance nursing quality.

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Objective To investigate the epidemiological and pathogenic characteristics of viral diarrhea in Minhang District, Shanghai. Methods Random sampling on diarrhea was conducted in intestinal outpatient departments of 2 sentinel hospitals according to a certain sampling interval in Minhang District，Shanghai from 2014 to 2020. Real time PCR technology was used to detect Rotavirus, Norovirus, adenovirus, Astrovirus and Sapovirus in fecal samples. Results A total of 646 out of 1 839 stool specimenswere tested positive, and the positive rate was 35.13%.Five pathogenic viruses were detected , mostly norovirus (421 cases, 65.17%) followed by rotavirus (151 cases, 23.37%).The positive rate of norovirus was higher in the age group of 20- 69 years, and the positive rate of Rotavirus was higher in the age group of 0- 9 years. Conclusions Norovirus and rotavirus accounted for the majority of reported infection diarrhea cases in MinhangDistrict of Shanghai from 2014 to 2020, with significant seasonal peaks. Tailored prevention and control measures should be carried out, particularly in risk seasons.

OBJECTIVE To es tablish the fingerprints of pith-nodecayed and pith-decayed Scutellaria baicalensis ，and to investigate the difference of their anti-inflammatory activities. METHODS HPLC method was adopted to establish the fingerprints of 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis . SIMCA 14.1 software was adopted to screen the markers of weight difference between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis ，using variable importance in projection （VIP）＞1 as standard. Using the inhibitory rates of NO ，IL-6 and IL- 1β in supernatant of lipopo- lysaccharide（LPS）-induced monocyte macrophages （RAW264.7 cells）as indexes ，the anti-inflammatory activities of pith-decayed and pith-nodecayed S. baicalensis were evaluated and median effective concentration （EC50）of NO were calculated. The gray correlation method was used for spectrum-effect relationship analysis ；SPSS 26.0 software was used for cluster analysis using the inhibitory rates of NO ，IL-6 and IL- 1β in cells at the concentration of 50 μg/mL. RESULTS There were 15 common peaks in 5 batches of pith-nodecayed S. baicalensis and 5 batches of pith-decayed S. baicalensis ，and the similarity of them was greater than 0.990. There were total of 8 peaks with VIP 1.0，they were peak 14，12，15，6，10，13，11 and 4. At jcqinge@163.com the concentration of 50 μg/mL，the inhibitory rates of pith- decayed S. baicalensis extract to NO ，IL-6，IL-1 β and the average EC 50 were 62.14％-71.13％，3.32％ -18.38％ and 93.12％-95.47％ and 25.35 μg/mL，respectively；those of pith-nodecayed S. baicalensis extract were 39.52％-50.19％， 6.21％-22.55％，94.10％-96.44％ and 58.63 μg/mL，respectively. Average NO inhibition rate of pith-decayed S. baicalensis extract was significantly higher than that of pith- nodecayed S. baicalensis extract；average EC 50 and average IL- 6 inhibitory rate of pith-decayed S. baicalensis extract were significantly lower than those of pith-nodecayed S. baicalensis extract（P＜0.05）. There was no statistical significance in average inhibitory rate of IL- 1β（P＞0.05）. The correlation degrees of peaks 2-3，5-8 and 10-11 with inhibitory rate of NO were all greater than 0.8. The correlation degrees of peaks 2，5，8-9 with inhibitory rate of IL- 1β were all greater than 0.9. The correlation degrees of 15 common peaks with inhibitory rate of IL- 6 were all less than 0.8. Ten batches of samples could be grouped into two categories ，K1-K5 were clustered into one category and T 12-T16 were clustered into one category. CONCLUSIONS At the concentration of 50 µg/mL，the inhibitory effect of pith-decayed S. baicalensis extract to NO is stronger than that of pith-nodecayed S. baicalensis extract，while the inhibitory effect on IL- 6 is weaker than that of pith-nodecayed S. baicalensis extract；they have similar inhibitory effect on IL- 1β. The corresponding components of peak 6，10-11 are preliminarily identified as main chemical components of the difference in anti-inflammatory activity between pith-decayed S. baicalensis and pith-nodecayed S. baicalensis .

Under the background of " Internet+ medical treatment" and the continuous deepening of face recognition technology research, the face recognition industry has continued to mature, and face recognition has been initially applied in medical fields such as hospital management, auxiliary medical care, and epidemic prevention and control. At the same time, face recognition technology brings problems including error risk, technical cracking risk, privacy risk, equality risk, abuse risk, and other issues in practice, which seriously threaten the personal and property rights and interests of the public. On the basis of summarizing the specific application direction of face recognition technology in hospitals, the authors sorted out the legal regulation of face recognition in China, and proposed that it should be based on technology research and development, strengthen the " gatekeeper" responsibility of medical institutions, improve legal system and recommendations for strengthening judicial leadership in order to improve the legal regulations of face recognition technology, reduce the risk of infringement by medical institutions in the application of face recognition technology, and protect the legitimate rights and interests of citizens.