OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

The Split-Cre system consists of two inactive polypeptides: NCre and CCre, which can be recombined into an active full-length Cre under certain conditions. This system is typically used with LoxP. To develop an efficient Split-Cre system, this study used Rma intein from Rhodothermus marinus to split Cre and screened out the split site S102 which could efficiently mediate the recombination of Cre in the "Traffic Light" reporter cell line. Moreover, the S102 Split-Cre system was delivered to mice by dual-adeno-associated virus (AAV), and it was demonstrated that the efficiency of the Rma intein-mediated S102 Split-Cre system was comparable to the full-length Cre in mice. This system lays a foundation for both basic and applied research on Split-Cre.
Inteins/genetics* ; Animals ; Integrases/biosynthesis* ; Mice ; Dependovirus/metabolism* ; Bacterial Proteins/genetics* ; Recombination, Genetic ; Humans

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.

Objective: To explore the relationship between depressive symptoms, negative life events and resilience among primary and secondary school teachers, so as to provide a reference for mental health promotion in school teachers. Methods: During November to December 2022, a questionnaire survey was conducted using convenient cluster sampling method to select 11 332 in service teachers from 38 schools in 8 provinces (cities) including Beijing, Guangdong, Anhui, Hubei, Sichuan, Xinjiang, Liaoning, and Heilongjiang. The Patient Health Questionnaire-9 items, a self developed 21-item Adverse Life Events questionnaire, and a 10-item Conner-Davidson Resilience Scale were used to assess depressive symptoms, experiences of negative life events, and resilience levels of the teachers, respectively. The relationship between depressive symptoms, negative life events and psychological resilience were analyzed by multiple linear regression and stratified regression. Results: The detection rate of depressive symptoms among primary and secondary school teachers was 14.0%. Negative life events of primary and secondary school teachers were positively correlated with depressive symptoms ( r =0.35), while psychological resilience was negatively correlated with depressive symptoms ( r =-0.45) ( P <0.05). After adjusting for possible covariates including gender and marital status, negative life events were positively correlated with depressive symptoms ( β=0.22, P <0.01). Resilience played a moderating role in the association of negative life events with depressive symptoms among primary and secondary school teachers ( B=-0.15, P <0.01). Conclusions Negative life events experiences are associated with higher level of depressive symptoms among school teachers. However, resilience might mitigate the negative effects of negative life events on depressive symptoms, playing a protective role in teachers mental health.

BACKGROUND:Hydroxyapatite is the main inorganic component of bone tissue.The polymer has the structure and function of a biomimetic extracellular matrix.The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE:To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS:The articles collected in PubMed,Web of Science,CNKI and WanFang databases were searched from January 2010 to April 2023.The Chinese and English search terms were"hydroxyapatite,polymer,composites,degradability,bone defect,bone repair".Finally,75 articles were included for review. RESULTS AND CONCLUSION:Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers(collagen,chitosan,alginate,serine protein,cellulose,hyaluronic acid,and polyhydroxybutyrate)and synthetic polymers[polylactic acid,polylactic acid-hydroxyacetic acid copolymer,poly(has-lactide),poly(amino acid)and poly(vinyl alcohol)].The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite.Hydroxyapatite composite with polymers can be made into porous scaffolds,hydrogels,and coatings for bone repair.Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function.Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins,repair materials with mechanical properties matching bone tissue,degradation processes synchronized with bone repair,and efficient osteogenesis and vascularization need to be further investigated.

Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.

Objective To investigate the mechanism by which Nicotinamide adenine dinucleotide(NADH)regu-lates anti-tuberculosis drug-induced liver injury and apoptosis in mice through SIRT1/Nrf2 pathway.Methods Twenty-four six-week-old SPF male mice were randomly divided into four groups according to body weight,ADLI group[90 mg/(kg·d)Isoniazid,135 mg/(kg·d)Rifampicin,315 mg/(kg·d)Pyrazinamide were given by gavage],control group[thesame volume of saline was given by gavage as antituberculosis drug-induced liver injury(ADLI)group],NADH group(30 mg/kg NADH wasgiven by gavage on the basis of control group)and NADH intervention group(30 mg/kg NADH wasgiven by gavage on the basis of ADLI group),with sixmice in each group.They were gavaged continuously for seven days,and their seruand liver tissues were collected.The mRNA and protein expression of silence information regulator 1(SIRT1),nuclear factor erythroid 2-related factor 2(Nrf2)in SIRT1/Nrf2 pathway,apoptosis indicators B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-3 were detected by qRT-PCR and Western blot,respectively.HE staining was performed to observe the morphology of liver tissue.The liver was weighedandthe liver index was obtained by dividingweight by body weight.The levels of glutamate aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),which are indicators of liver injury,were detected by microplate method.Results Compared with control group,the protein and mRNA expression of SIRT1,Nrf2decreased significantly in ADLI group.Liver tissue struc-ture wasdisturbed,hepatocytes were obviously swollen,and their boundary was unclear.The weight of mice de-creased,but liver index increased.The mRNA and protein expression level of anti-apoptotic factor Bcl-2 decreased,while that of Bax and caspase-3 was raised.The level of ALT,AST and LDH were also elevated.The differences a-bove were statistically significant(P＜0.05).Compared with ADLI group,the protein and mRNA expression of SIRT1,Nrf2 were higher after NADH intervention.Liver tissue structure became clear,and hepatocytes were po-lygonal.The protein and mRNA expression of anti-apoptosis factor Bcl-2 was elevated and while that of Bax and caspase-3 was lower.The weight of mice increased and liver index decreased.The expression of ALT,AST and LDH decreased.The differences above were statistically significant(P＜0.05).Conclusion NADH may allevi-ate anti-tuberculosis drug-induced liver injury and apoptosis in mice by regulating SIRT1/Nrf2 pathway.

Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.