Objective To investigate the role of cellular autophagy in medullary thyroid carcinoma (MTC) under doxorubicin (DOX)-induced stress and chemoresistance and to evaluate the synergistic antitumor effect of combining the autophagy inhibitor chloroquine (CQ) with DOX. Methods The human MTC cell line TT was used as an in vitro model and assigned to four groups: control, DOX, CQ, and DOX+CQ combination. Autophagy flux was assessed by Western blot analysis of LC3-Ⅱ protein expression, whereas autophagic structures were observed through transmission electron microscopy (TEM). An MTC xenograft model was established in nude mice, and tumor-bearing mice were randomly allocated to corresponding treatment groups. Tumor growth volume and weight were monitored, and autophagy levels in tumor tissues were detected. Results In vitro experiments showed that DOX treatment considerablyincreased LC3-Ⅱ levels, indicating autophagy induction. The combination of DOX and CQ led to further LC3-Ⅱaccumulation, and TEM revealed numerous undegraded autophagosomes and abnormal autolysosomes, confirming the successful blockade of autophagic flux. In vivo, the DOX+CQ combination therapy inhibited tumor growth significantly more effectively than any single-agent treatment (tumor inhibition rate: 60.0%, P<0.01) without causing considerable systemic toxicity. Marked accumulation of LC3-Ⅱ in tumor tissues from the combination group indicated the effective inhibition of autophagic flux in vivo. Conclusion Functional autophagy flux is a key mechanism underlying DOX chemoresistance in MTC. CQ can effectively reverse this resistance by blocking autophagic flux, and its combination with DOX exhibits a considerable synergistic antitumor effect. These findings suggest a promising therapeutic strategy for the management of advanced MTC.

Objective To investigate whether Danshen injection (DSI) can protect human brain organoids from oxidative stress damage by regulating the Nrf2 signaling pathway and its mechanism. Methods A Nrf2 plasmid was constructed, lentivirus was packaged and transfected into human induced pluripotent stem cell (hiPSC) to form a stable cell line. Brain organoids with Nrf2 overexpression (LV-Nrf2 group) and knockdown (sh-Nrf2 group) were constructed using kit. The transfection efficiency was verified by real-time fluorescence quantitative polymerase chain reaction. An oxidative stress injury model was established by inducing hydrogen peroxide (H₂O₂). Intervention was performed either in combination or without DSI pre-treatment. Cell viability was detected by Cell Counting Kit-8 (CCK-8), and the expression levels of Nrf2, malondialdehyde (MDA), interleukin (IL)-1β, sex-determining region Y-box protein 2 (SOX2) and neuronal-specific nuclear protein (NeuN) were detected by Western blot and immunofluorescence staining. Total RNA from human brain organoids was extracted for transcriptome sequencing and analysis. Results LV-Nrf2 group and sh-Nrf2 group brain organoid models were successfully constructed. The CCK-8 results determined that the oxidative stress model was established with 32 mmol/L H₂O₂ intervention conditions. The fluorescence expression of Nrf2 in LV-Nrf2 group was higher than that in control group, and the fluorescence expressions of MDA and IL-1β were lower than those in control group; sh-Nrf2 group showed a damage phenotype of low Nrf2 expression, high MDA and IL-1β expression (all P < 0.05). Compared with H₂O₂ group, the Nrf2 signal in DSI + H₂O₂ group was stronger, and the levels of MDA and IL-1β were lower. Among them, the protective effect of LV-Nrf2 was the most significant. H₂O₂ treatment could down-regulate the protein levels of Nrf2, SOX2 and NeuN, and DSI intervention could effectively reverse the downward trend of these indicators. Sh-Nrf2 could weaken the recovery effect of DSI on SOX2 and NeuN, while LV-Nrf2 could synergistically enhance the regulatory effect of DSI. Conclusions DSI may antagonize oxidative stress damage in human brain organoids through the Nrf2 signaling pathway, and maintaining the stability of the neural cell lineage is its core therapeutic characteristic.

Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.

Objective:To evaluate the diagnostic value of metagenomic next-generation sequencing（mNGS）in bone and joint infections caused by non-tuberculous mycobacteria（NTM）.Methods:Clinical data of 175 patients with suspected NTM bone and joint infections admitted in Beijing Chest Hospital，Capital Medical University from January 2019 to January 2023 were retrospectively analyzed. Mycobacterium growth indicator tube（MGIT）method was used for mycobacterial culture on the bone tissue or abscess samples and mNGS test was performed on bone tissue samples in all patients. Taking clinical diagnosis as the gold standard，the sensitivity，specificity，positive predictive value，negative predictive value，positive likelihood ratio，and negative likelihood ratio of the two methods were compared.Results:Twenty-six patients（14.9%）were clinically diagnosed as NTM bone and joint infections. The mNGS showed higher sensitivity（100.0% vs. 57.7%，），specificity（99.3% vs. 86.6%），positive predictive value（96.3% vs. 42.9%），and negative predictive value（100.0% vs. 92.1%），compared to MGIT culture（all P<0.001）. The positive likelihood ratio（149.00 vs. 4.31）and negative likelihood ratio（0 vs. 0.49）of mNGS were also superior to those of MGIT. Conclusion:Compared to MGIT culture，mNGS has high diagnostic value in NTM bone and joint infections and can serve as an efficient and reliable method for clinical diagnosis.

This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

Objective:To construct a risk prediction model for radiation dermatitis in the perineum of cervical cancer patients undergoing radiotherapy, and verify the predictive effect of the model, so as to provide theoretical basis for reducing the risk of perineal radiation dermatitis in clinical practice.Methods:A prospective study design was used to conveniently select 247 cervical cancer patients who received radiotherapy at Tianjin Medical University Cancer Institute & Hospital from January 2022 to March 2023 as the modeling group. They were divided into a group with perineal radiodermatitis ( n = 130) and a group without perineal radiodermatitis ( n = 117). The data of the two groups were compared, and a risk prediction model was constructed based on the results of logistic regression analysis. Used the area under the receiver operating characteristic (ROC) curve to test the predictive performance of the model. From May to November 2023, 109 patients were selected as the validation group to conduct external validation of the model. Results:Among the 247 patients in the modeling group, the age of the group with perineal radiodermatitis was (45.31 ± 7.25) years old, and the age of the group without perineal radiodermatitis was (46.70 ± 6.43) years old. The incidence of perineal radiation dermatitis during radiotherapy in the modeling group was 52.6% (130/247), while in the validation group it was 44.0% (48/109). The final predictive variables included in the model were high blood sugar or not ( OR = 0.304, 95% CI 0.174-0.530), vaginal bleeding/discharge or not ( OR = 4.338, 95% CI 2.397-7.854), involvement of 1/3 of the vagina or not ( OR = 0.497, 95% CI 0.281-0.879), whether topical skin protectants could be used( OR = 3.479, 95% CI 1.596-7.583), whether skin protectants could be used in a standardized manner ( OR = 2.399, 95% CI 1.201-4.789), whether the skin could be cleaned with the correct cleaning agent ( OR = 3.155, 95% CI 1.603-6.209), and whether the skin could be wiped with the correct method ( OR = 3.325, 95% CI 1.806-6.121), totaling 7 predictive factors (all P<0.05). The area under the ROC curve of the prediction model was 0.866, the sensitivity was 0.735, and the specificity was 0.852, the Youden index was 0.587. Model validation results showed the area under the ROC curve was 0.762, the sensitivity was 0.815, the specificity was 0.717, and the accuracy was 80.73%, indicating good predictive performance. Conclusions:The predictive model constructed in this study had good predictive performance and could provide reference for clinical nursing staff to screen high-risk patients with perineal radiation dermatitis.

Objective:To construct a risk prediction model for radiation dermatitis in the perineum of cervical cancer patients undergoing radiotherapy, and verify the predictive effect of the model, so as to provide theoretical basis for reducing the risk of perineal radiation dermatitis in clinical practice.Methods:A prospective study design was used to conveniently select 247 cervical cancer patients who received radiotherapy at Tianjin Medical University Cancer Institute & Hospital from January 2022 to March 2023 as the modeling group. They were divided into a group with perineal radiodermatitis ( n = 130) and a group without perineal radiodermatitis ( n = 117). The data of the two groups were compared, and a risk prediction model was constructed based on the results of logistic regression analysis. Used the area under the receiver operating characteristic (ROC) curve to test the predictive performance of the model. From May to November 2023, 109 patients were selected as the validation group to conduct external validation of the model. Results:Among the 247 patients in the modeling group, the age of the group with perineal radiodermatitis was (45.31 ± 7.25) years old, and the age of the group without perineal radiodermatitis was (46.70 ± 6.43) years old. The incidence of perineal radiation dermatitis during radiotherapy in the modeling group was 52.6% (130/247), while in the validation group it was 44.0% (48/109). The final predictive variables included in the model were high blood sugar or not ( OR = 0.304, 95% CI 0.174-0.530), vaginal bleeding/discharge or not ( OR = 4.338, 95% CI 2.397-7.854), involvement of 1/3 of the vagina or not ( OR = 0.497, 95% CI 0.281-0.879), whether topical skin protectants could be used( OR = 3.479, 95% CI 1.596-7.583), whether skin protectants could be used in a standardized manner ( OR = 2.399, 95% CI 1.201-4.789), whether the skin could be cleaned with the correct cleaning agent ( OR = 3.155, 95% CI 1.603-6.209), and whether the skin could be wiped with the correct method ( OR = 3.325, 95% CI 1.806-6.121), totaling 7 predictive factors (all P<0.05). The area under the ROC curve of the prediction model was 0.866, the sensitivity was 0.735, and the specificity was 0.852, the Youden index was 0.587. Model validation results showed the area under the ROC curve was 0.762, the sensitivity was 0.815, the specificity was 0.717, and the accuracy was 80.73%, indicating good predictive performance. Conclusions:The predictive model constructed in this study had good predictive performance and could provide reference for clinical nursing staff to screen high-risk patients with perineal radiation dermatitis.

Objective:To evaluate the diagnostic value of metagenomic next-generation sequencing（mNGS）in bone and joint infections caused by non-tuberculous mycobacteria（NTM）.Methods:Clinical data of 175 patients with suspected NTM bone and joint infections admitted in Beijing Chest Hospital，Capital Medical University from January 2019 to January 2023 were retrospectively analyzed. Mycobacterium growth indicator tube（MGIT）method was used for mycobacterial culture on the bone tissue or abscess samples and mNGS test was performed on bone tissue samples in all patients. Taking clinical diagnosis as the gold standard，the sensitivity，specificity，positive predictive value，negative predictive value，positive likelihood ratio，and negative likelihood ratio of the two methods were compared.Results:Twenty-six patients（14.9%）were clinically diagnosed as NTM bone and joint infections. The mNGS showed higher sensitivity（100.0% vs. 57.7%，），specificity（99.3% vs. 86.6%），positive predictive value（96.3% vs. 42.9%），and negative predictive value（100.0% vs. 92.1%），compared to MGIT culture（all P<0.001）. The positive likelihood ratio（149.00 vs. 4.31）and negative likelihood ratio（0 vs. 0.49）of mNGS were also superior to those of MGIT. Conclusion:Compared to MGIT culture，mNGS has high diagnostic value in NTM bone and joint infections and can serve as an efficient and reliable method for clinical diagnosis.

This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.