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*

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Background The power industry is characterized by typical shift work systems, with 24-hour uninterrupted work demands, high intensity and high standard job characteristics, as well as emergent task pressure, which exposes employees to the long-term dual pressure of shift work and occupational stress and may lead to occupational burnout. It not only endangers the physical and mental health of employees, but also threaten the safe and stable operation of the power system. Objective To explore the impact of shift work and occupational stress, as well as their potential interaction, on occupational burnout among employees in power enterprises. Methods From November 2024 to April 2025, cluster sampling was used to select 1378 workers from two power companies in Fuzhou. A self-designed questionnaire, the Effort-Reward Imbalance model, and the Maslach Burnout Inventory were used to investigate the participants’ general information，shift work patterns, occupational stress, and occupational burnout. Statistical analysis was conducted using SPSS 19.0 software. Chi-square test was employed for intergroup comparison. Logistic regression was used to examine the associations between shift work, occupational stress, and job burnout. The multiplicative interaction and additive interaction between shift work and occupational stress on occupational burnout were evaluated. Results A total of 1378 questionnaires were distributed, and 1113 were valid questionnaires, with an effective rate of 80.77%. Among the participants, 37.92% were engaged in shift work, the positive rate of occupational stress was 29.83%, and the positive rate of occupational burnout was 55.80%. The logistic regression analysis showed that after adjusting for confounding factors, the risks of occupational burnout in the non-shift x occupational stress group and the shift x occupational stress group were 1.59 times (95%CI: 1.12, 2.27; P=0.01) and 4.07 times (95%CI: 2.56, 6.45; P<0.01) higher than that in the non-shift x non-occupational stress group. A multiplicative interaction (shift work and occupational stress b=0.75, P=0.01, OR=2.12, 95%CI: 1.18, 3.80) and an additive interaction (relative excess risk ratio=2.24, 95%CI: 0.54, 3.94; attributable fraction=0.55, 95%CI: 0.32, 0.78; interaction index=3.71, 95%CI: 1.47, 9.40) between shift work and occupational stress on job burnout were identified. Conclusion Shift work and occupational stress are risk factors for occupational burnout among employees in power enterprises, and there is a synergistic interaction between these two factors in terms of their impact on occupational burnout.

Objective:To investigate the effect of spinopelvic sagittal alignment and lordosis distribution index on adjacent segment degeneration (ASD) after short-segment lumbar interbody fusion.Methods:A total of 234 patients who underwent posterior lumbar interbody fusion due to lumbar degenerative diseases in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University and Affiliated Drum Tower Hospital, Medical School of Nanjing University from January 2009 to January 2019 were retrospectively analyzed. There were 102 males and 132 females, aged 60.1±10.0 years (range, 41-78 years). The patients were divided into ASD group and non-ASD group according to whether ASD occurred after operation. The general data, pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), distal lordosis (DL), segmental lordosis (SL), lordosis distribution index (LDI) and sagittal vertical axis (SVA) before and after operation were compared between the two groups. Independent risk factors for the occurrence of ASD after lumbar fusion were analyzed using binary logistic regression. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve was calculated for each independent risk factor.Results:All patients successfully completed the operation and were followed up for 70.6±11.9 months (range, 60-121 months). Among the 234 patients, 116 patients developed ASD after operation. Age ( t=2.697, P=0.008), fusion segment (χ 2=16.439, P<0.001), preoperative PT ( t=2.268, P=0.024), preoperative LL ( t=2.042, P=0.042), preoperative DL ( t=2.724, P=0.007), postoperative DL ( t=3.104, P=0.002), postoperative LDI ( t=2.063, P=0.040) and the difference of SVA before and after operation ( Z=2.001, P=0.045) were statistically significant. Binary logistic regression analysis showed that LDI decreased ( OR=0.971, P=0.002), two-level fusion ( OR=3.477, P<0.001), and increased SVA difference before and after operation ( OR=0.992, P=0.039) were independent risk factors for ASD after lumbar fusion. The ROC curve showed that the area under the curve and 95% CI of the number of fusion segments, postoperative LDI, and the difference of SVA before and after operation were 0.633 (0.561, 0.704), 0.583 (0.510, 0.656) and 0.576 (0.502, 0.649), respectively. The area under the curve of the combined prediction model was 0.702, and the prediction value was medium. Conclusion:Two-level fusion, decreased LDI after operation, and increased SVA difference before and after operation are independent risk factors for ASD after lumbar fusion, and the combined prediction of the three has good predictive efficiency.

Objective:Hypoxia is an important cause of chemotherapy resistance in gastric cancer.However,little is known about the growth of gastric cancer under purely hypoxia conditions.This study aims to study the effect of hypoxia on the growth patterns of gastric cancer cells and explore the response of gastric cancer cells to the chemotherapeutic drug 5-fluorouracil(5-FU)in a hypoxic environment. Methods:Gastric cancer cells MKN45 were cultured under 1%oxygen hypoxia and conventional air conditions.An intervention group with the addition of the chemotherapeutic drug 5-FU was also established.The proliferation and apoptosis of gastric cancer cells under different oxygen conditions and intervention groups were detected using the cell counting kit-8(CCK-8)method,JC-1 mitochondrial membrane potential assay,and Annexin-V/PI double staining method.Cell cycle changes were detected by flow cytometry,and mitochondrial changes were detected using electron microscopy. Results:In the absence of 5-FU intervention,compared with the normoxia group,the hypoxia group showed higher rates of early and late apoptosis and higher cell death rates as indicated by the JC-1 mitochondrial membrane potential assay,Annexin-V/PI double staining,and CCK-8 results.Flow cytometry results showed that the cell cycle was arrested in the G0/G1 phase without progression.Electron microscopy revealed more severe mitochondrial destruction.However,with 5-FU intervention,the hypoxia group showed lower apoptosis rates,more cell cycle progression,and less mitochondrial destruction compared with the normoxia group. Conclusion:Hypoxic environments promote apoptosis and even death in gastric cancer cells,but hypoxia counteracts the efficacy of the chemotherapeutic drug 5-FU,which may contribute to 5-FU chemotherapy resistance.

Peripheral pulmonary lesions(PPL),including peripheral pulmonary nodules,are common lung problems.As the increase of patients with lung nodules,the demand for tissue sampling also increases.Safe and accurate biopsy techniques are very important for patients to identify benign and malignant lesions.Electronic bronchoscopy is one of the biopsy techniques for the diagnosis of PPL in recent decades.Various guiding techniques,such as radial probe endobronchial ultrasound and virtual navigation bronchoscope,have been proved to improve the performance of conventional bronchoscopy.This paper aims to provide an review of the available data on advanced bronchoscopic techniques and explore their application in diagnosing PPL.

Objective To summarize the clinical effect and adverse reactions of avatrombopag combined with tacrolimus in the treatment of elderly patient with refractory severe aplastic anemia. Methods An elderly patient with refractory severe aplastic anemia was treated with avatrombopag and tacrolimus, and the literature review on the mechanism of action and safety of avatrombopag and tacrolimus was conducted. Results The patient was treated with a combination of cyclosporine, testosterone undecanoate, and itraconazole for 6 months without success, and developed liver and kidney dysfunction. The medication was discontinued, and the patient was treated with a combination of avatrombopag (20 mg, once per day) and tacrolimus (1 mg, twice per day). After 9 months of treatment, the patient's platelet count increased to 54×10⁹/L, the hemoglobin increased to 124 g/L, the white blood cells increased to 8.23×10⁹/L, liver and kidney function also returned to normal level, and no other adverse reactions such as thrombotic events were observed. After treatment, CD4/CD8 decreased, CD8⁺ T cells increased, and the proportion of Treg cells increased as well. Conclusion The combination of avatrombopag and tacrolimus is effective and well tolerated in the treatment of elderly patient with refractory aplastic anemia, but the long-term follow-up observation and continued accumulation of cases are still needed in the future.

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Deacetylation of chitin is closely related to insect development and metamorphosis. Chitin deacetylase (CDA) is a key enzyme in the process. However, to date, the CDAs of Bombyx mori (BmCDAs), which is a model Lepidopteran insect, were not well studied. In order to better understand the role of BmCDAs in the metamorphosis and development of silkworm, the BmCDA2 which is highly expressed in epidermis was selected to study by bioinformatics methods, protein expression purification and immunofluorescence localization. The results showed that the two mRNA splicing forms of BmCDA2, namely BmCDA2a and BmCDA2b, were highly expressed in the larval and pupal epidermis, respectively. Both genes had chitin deacetylase catalytic domain, chitin binding domain and low density lipoprotein receptor domain. Western blot showed that the BmCDA2 protein was mainly expressed in the epidermis. Moreover, fluorescence immunolocalization showed that BmCDA2 protein gradually increased and accumulated with the formation of larval new epidermis, suggesting that BmCDA2 may be involved in the formation or assembly of larval new epidermis. The results increased our understandings to the biological functions of BmCDAs, and may facilitate the CDA study of other insects.
Animals ; Bombyx/metabolism* ; Metamorphosis, Biological/genetics* ; Larva/metabolism* ; Gene Expression ; Insect Proteins/metabolism* ; Chitin

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.