The Proctor's reporting guideline for implementation strategies represents a landmark framework in the field of implementation science, aiming to address the issue of inconsistent reporting in implementation research by standardizing the naming, definition, and operationalization of implementation strategies, thereby enhancing the credibility and utility of research findings. This paper provides an in-depth interpretation of the core connotations of this reporting guideline and illustrates its application in developing interview outlines and specifying implementation strategies, using a brief smoking cessation intervention project as a case study. Through this reporting guideline, abstract recommendations for implementation are systematically transformed into clear, multidimensional operational guides, significantly improving the transparency of strategy connotations and the replicability of actual execution. Meanwhile, the case study highlights the flexibility of the guideline, which allows researchers to adapt the content and format of strategies based on local resources and cultural contexts, thus enhancing practical adaptability while maintaining scientific rigor. However, the application of Proctor's reporting guideline still faces challenges, primarily manifested in the potential confusion surrounding the constructs of temporality and dose in practice, as well as the challenges that the inherent flexibility of the guideline may pose to the assessment of fidelity and effectiveness. Despite these limitations, the reporting guideline remains a vital tool for implementation research; future efforts should focus on optimizing its application—through refining operational guidelines, standardizing flexible adaptations, and involving stakeholders—to better guide implementation studies and continuously promote high-quality development in the field.

OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 （PD-1） inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma （HCC）. METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them， 89 patients received PD-1 inhibitors （tislelizumab or sintilimab， similarly hereinafter） plus vascular intervention （control group） and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention （observation group）. Short-term efficacy （3 months after treatment）， long-term efficacy （2 years after treatment）， the levels of liver function indexes [serum alanine amino-transferase （ALT）， aspartate transferase （AST）， and total bilirubin （TBil）] and tumor biomarkers [alpha fetoprotein （AFP）， carcinoembryonic antigen （CEA）， carbohydrate antigen 19-9 （CA19-9）， and des-gamma-carboxy prothrombin （DCP）] before treatment and after 3 months of treatment， as well as the occurrence of adverse drug reaction （ADR） during treatment， were compared between the two groups. In addition， overall response rate （ORR） stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment， the ORR was significantly higher in the observation group than in the control group （P＜0.05）； although the disease control rate was higher in the observation group compared to the control group， the difference was not statistically significant （P＞0.05）. The median overall survival of patients in the observation group was 16.9 months [95% confidence interval （CI）： 14.2 to 19.1 months]， which was significantly longer than that in the control group （12.4 months， 95%CI： 10.1 to 15.3 months） （P＜0.05）. Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups， with no significant heterogeneity （P＞0.1， I 2＜0.001%）. Before treatment， there were no significant differences in liver function indexes or tumor marker levels between 2 groups （P＞0.05）. After treatment， both groups showed significant declines in these indicators compared with baseline （P＜0.05）， with greater reductions observed in the observation group （P＜0.05）. There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups （P＞0.05）. CONCLUSIONS For patients with unresectable HCC， the combination of donafenib， PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.

With the increase in the obese population and the aging of the society,the incidence rates of type 2 diabetes mellitus(T2DM)and obstructive sleep apnea(OSA)continue to increase,and more than half of the patients with T2DM also suffer from OSA.T2DM patients with OSA have a higher risk of developing macrovascular and microvascular complications,which severely impairs their quality of life,and early identification of T2DM patients with OSA can improve their prognosis.This article summarizes the latest re-search advances in the pathogenesis,biomarkers,and treatment measures of T2DM with OSA,in order to provide insights for the screening,diagnosis,and treatment of T2DM with OSA.

Objective:To determine the optimal irradiation energy and frequency for the establishment of melasma mouse model using simple ultraviolet irradiation, and to provide guidance on animal strains and irradiation protocols for the successful establishment of melasma model.Methods:Animal models of melasma were established using BALB/c female mice and C57BL/6JNifdc female mice. BALB/c female mice were divided into 4 groups using a simple randomization method: A, B, C and G, with 5 mice in each group. C57BL/6JNifdc female mice were divided into 4 groups: D, E, F and H, with 5 mice in each group. All mice were irradiated with 8.428 mW/cm 2 of ultraviolet light. The irradiation time was 15 s (single irradiation energy of 0.13 J/cm 2) in groups A and D, 15 min (single irradiation energy of 7.59 J/cm 2) in groups B and E, and 30 min (single irradiation energy of 15.17 J/cm 2) in groups C and F. Each cycle consisted of 5 consecutive days of irradiation followed by 2 days of cessation, totaling 4 cycles of irradiation. Groups G and H were not irradiated. At the end of irradiation, all mice were kept under normal conditions. One week later, 3 mice from each group were selected for HE, Masson-Fontana, Masson, and immunohistochemical staining. Quantitative analysis was performed to measure the thickness of the acanthocyte layer, melanin granules, collagen percentage, and interleukin-1 (IL-1) levels. The remaining mice were kept for an additional week, depilated and photographed to observe the changes in coloration. Data were analyzed using SPSS 27.0 software, measurement data that did not conform to normal distribution were represented by M( Q1, Q3) and comparisons between groups were made using the Kruskal-Wallis rank sum test. Results:During the entire irradiation process, no visible discoloration was observed in the BALB/c female mice in all groups. In contrast, varying sizes of discoloration appeared in the C57BL/6JNifdc female mice in groups D, E, and F after irradiation in the second week. However, by the third week, the discoloration in group D gradually disappeared, while the discoloration in group E was more obvious than before. At the same time, group F exhibited significant discoloration, with some mice exhibited signs of skin peeling, burning and breakage on their backs. After the 4th week of irradiation, no new discoloration was formed in group D. The discoloration was more obvious in group E, and most mice in group F showed skin burn breakage. Two weeks after the completion of irradiation, there was no obvious discoloration on the dorsal skin of BALB/c female mice in all groups. In C57BL/6JNifdc female mice, group D showed no obvious discoloration, group E exhibited lighter discoloration compared to the 4th week post-irradiation, and group F had crusted skin at the burn sites with lighter discoloration than before. However, the discoloration in groups E and F was still obviously visible to the naked eye. HE staining showed that the difference in the thickness of the echinocyte layer was not statistically significant in groups A, B, C, and G ( H=1.08, P=0.782); whereas the difference was statistically significant in groups D, E, F and H ( H=12.85, P=0.005). The thickness of the echinocyte layer decreased gradually with the extension of the irradiation time. Additionally, there was a disruption in the arrangement of epidermal spindles in group F, and this situation was not observed in groups D and E. Masson-Fontana staining revealed no significant pigmentation in any of the BALB/c female mice. The difference in melanin granule counts between groups A, B, C, and G was not statistically significant ( H=7.77, P=0.051). In contrast, C57BL/6JNifdc female mice exhibited more noticeable pigmentation in the epidermis and dermis in groups E and F. The difference in melanin particle counts among groups D, E, F and H was statistically significant ( H=17.61, P<0.001), with melanin deposition increasing gradually with the duration of irradiation. Masson staining showed that the difference in collagen percentage between groups A, B, C, and G was not statistically significant ( H=7.26, P=0.064). However, significant disorganization of fibers and a loose structure were observed in groups E and F. The difference in collagen percentage between groups D, E, F, and H was statistically significant ( H=8.65, P=0.034). Immunohistochemical results showed that the difference in IL-1 expression levels between groups A, B, C, and G was statistically significant ( H=17.86, P<0.001); also between groups D, E, F, and H was statistically significant ( H=14.19, P=0.003), suggesting that ultraviolet irradiation stimulated an inflammatory response in the skin of mice. Conclusion:BALB/c female mice are not suitable for melasma models under the frequency and duration of irradiation in this experiment. C57BL/6JNifdc female mice are irradiated with a single irradiation energy dose of 7.59 J/cm 2 five days a week for 4 weeks, which can establish stable animal models of melasma with a specific level of pigmentation that persisted for at least 2 weeks.

Objective To explore the automated identification and diameter measurement methods for inferior vena cava (IVC) based on clinical ultrasound images of IVC. Methods An automated identification and localization method based on topology and automatic tracking algorithm was proposed. Tracking algorithm was used for identifying and continuously locating to improve the efficiency and accuracy of measurement. Tests were conducted on 18 sets of ultrasound data collected from 18 patients in intensive care unit (ICU),with clinicians' measurements as the gold standard. Results The recognition accuracy of the automated method was 94.44％ (17/18),and the measurement error of IVC diameter was within the range of±1.96s (s was the standard deviation). The automated method could replace the manual method. Conclusion The proposed IVC automated identification and localization algorithm based on topology and automatic tracking algorithm has high recognition success rate and IVC diameter measurement accuracy. It can assist clinicians in identifying and locating IVC,so as to improve the accuracy of IVC measurement.

Objective:To determine the optimal irradiation energy and frequency for the establishment of melasma mouse model using simple ultraviolet irradiation, and to provide guidance on animal strains and irradiation protocols for the successful establishment of melasma model.Methods:Animal models of melasma were established using BALB/c female mice and C57BL/6JNifdc female mice. BALB/c female mice were divided into 4 groups using a simple randomization method: A, B, C and G, with 5 mice in each group. C57BL/6JNifdc female mice were divided into 4 groups: D, E, F and H, with 5 mice in each group. All mice were irradiated with 8.428 mW/cm 2 of ultraviolet light. The irradiation time was 15 s (single irradiation energy of 0.13 J/cm 2) in groups A and D, 15 min (single irradiation energy of 7.59 J/cm 2) in groups B and E, and 30 min (single irradiation energy of 15.17 J/cm 2) in groups C and F. Each cycle consisted of 5 consecutive days of irradiation followed by 2 days of cessation, totaling 4 cycles of irradiation. Groups G and H were not irradiated. At the end of irradiation, all mice were kept under normal conditions. One week later, 3 mice from each group were selected for HE, Masson-Fontana, Masson, and immunohistochemical staining. Quantitative analysis was performed to measure the thickness of the acanthocyte layer, melanin granules, collagen percentage, and interleukin-1 (IL-1) levels. The remaining mice were kept for an additional week, depilated and photographed to observe the changes in coloration. Data were analyzed using SPSS 27.0 software, measurement data that did not conform to normal distribution were represented by M( Q1, Q3) and comparisons between groups were made using the Kruskal-Wallis rank sum test. Results:During the entire irradiation process, no visible discoloration was observed in the BALB/c female mice in all groups. In contrast, varying sizes of discoloration appeared in the C57BL/6JNifdc female mice in groups D, E, and F after irradiation in the second week. However, by the third week, the discoloration in group D gradually disappeared, while the discoloration in group E was more obvious than before. At the same time, group F exhibited significant discoloration, with some mice exhibited signs of skin peeling, burning and breakage on their backs. After the 4th week of irradiation, no new discoloration was formed in group D. The discoloration was more obvious in group E, and most mice in group F showed skin burn breakage. Two weeks after the completion of irradiation, there was no obvious discoloration on the dorsal skin of BALB/c female mice in all groups. In C57BL/6JNifdc female mice, group D showed no obvious discoloration, group E exhibited lighter discoloration compared to the 4th week post-irradiation, and group F had crusted skin at the burn sites with lighter discoloration than before. However, the discoloration in groups E and F was still obviously visible to the naked eye. HE staining showed that the difference in the thickness of the echinocyte layer was not statistically significant in groups A, B, C, and G ( H=1.08, P=0.782); whereas the difference was statistically significant in groups D, E, F and H ( H=12.85, P=0.005). The thickness of the echinocyte layer decreased gradually with the extension of the irradiation time. Additionally, there was a disruption in the arrangement of epidermal spindles in group F, and this situation was not observed in groups D and E. Masson-Fontana staining revealed no significant pigmentation in any of the BALB/c female mice. The difference in melanin granule counts between groups A, B, C, and G was not statistically significant ( H=7.77, P=0.051). In contrast, C57BL/6JNifdc female mice exhibited more noticeable pigmentation in the epidermis and dermis in groups E and F. The difference in melanin particle counts among groups D, E, F and H was statistically significant ( H=17.61, P<0.001), with melanin deposition increasing gradually with the duration of irradiation. Masson staining showed that the difference in collagen percentage between groups A, B, C, and G was not statistically significant ( H=7.26, P=0.064). However, significant disorganization of fibers and a loose structure were observed in groups E and F. The difference in collagen percentage between groups D, E, F, and H was statistically significant ( H=8.65, P=0.034). Immunohistochemical results showed that the difference in IL-1 expression levels between groups A, B, C, and G was statistically significant ( H=17.86, P<0.001); also between groups D, E, F, and H was statistically significant ( H=14.19, P=0.003), suggesting that ultraviolet irradiation stimulated an inflammatory response in the skin of mice. Conclusion:BALB/c female mice are not suitable for melasma models under the frequency and duration of irradiation in this experiment. C57BL/6JNifdc female mice are irradiated with a single irradiation energy dose of 7.59 J/cm 2 five days a week for 4 weeks, which can establish stable animal models of melasma with a specific level of pigmentation that persisted for at least 2 weeks.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.