BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective To observe the effect of cluster emergency nursing in treating patients with chlorfenapyr poisoning. Methods A retrospective analysis was performed for the treatment and nursing processes of 6 patients with chlorfenapyr poisoning. Results Among the 6 patients with chlorfenapyr poisoning, 5 cases were orally poisoned and one case was poisoned by respiratory tract and skin absorption of toxins. All of the 6 patients with chlorfenapyr poisoning were treated through the green channel for poisoning treatment, and multidisciplinary cooperation cluster treatment and nursing as well as toxicant detection were carried out. One patient was excluded because no chlorfenapyr component was detected in the toxicant detection; the remaining 5 patients had different degrees of fever, fatigue, nausea and vomiting and other symptoms in the early stage, and among them, 4 patients had high fever and aggravated degree of consciousness disturbance in the later stage of the disease, and died of ineffective treatment for 2 to 11 days after poisoning (one patient was out of contact and was expected to die), with a mortality rate of 80%. Conclusion There is no specific antidote for chlorfenapyr poisoning, and the mortality rate is extremely high. After poisoning, blood, urine and other specimens should be collected as soon as possible for toxic examination. At the same time, early gastric lavage (within 6 hours), intestinal adsorption, gastrointestinal catharsis, enema and other symptomatic treatments should be given. Continuous blood purification should be performed as soon as possible to remove blood toxins, and extracorporeal membrane oxygenation can be performed if conditions permit.

Objective To analyze the coding quality of multiple primary malignant tumors in a tertiary hospital,identify existing problems,and improve the accuracy of coding for multiple primary malignant tumors.Methods We collected 393 medi-cal records from a tertiary hospital from June 1,2021,to June 30,2023,with ICD-10 code C97 for the discharge diagnosis.By carefully reading the medical records,we analyzed the reasons for coding errors in multiple primary malignant tumors with code C97.Results Among the 393 medical records,there were 34 cases with coding errors in C97,including 11 cases where meta-static malignant tumors were erroneously coded as multiple primary malignant tumors,9 cases where malignant tumors of the same organ system with non-adjacent sites and the same histological type were erroneously coded as multiple primary malignant tumors,7 cases where distant metastasis or local invasion was erroneously coded as multiple primary malignant tumors,4 cases where be-nign tumors were mistakenly coded as malignant tumors,and 3 cases where suspected malignant tumors were coded as confirmed cases.Conclusion To improve the quality and efficiency of C97 coding,coders need to have a clear understanding of the defini-tion of multiple primary malignant tumors,read the medical records carefully and completely,determine the location and histolog-ical type of the tumors accurately,and strengthen communication with clinical physicians.

Coding malignant tumors in multiple sites within the digestive system involves some coding rules.When more than two malignant tumors present various pathologic types,they should be included in the code of C97,which indicates multiple primary malignancies,and should be categorized into a specific code under the category of C97 upon corresponding treatment pur-poses.For those malignant tumors in the digestive system presenting with the same pathological results but unidentified primary sites,which are diagnosed as more than two types of tumors and recorded on the first page of a medical record,they are coded ac-cording to their specific locations.The coding principles are as followed:① If a malignant tumor spans two or more adjacent sites with an unidentified primary origin,it should be classified as a cross-site malignant tumor and coded based on the tumor's ana-tomical location.② If more than two malignant tumors are located in the separate parts of the same location,they should be co-ded with".9"as a subheading of the three-digit category specific to the right location.③If more than two malignant tumors are not adjacent to each other in the digestive system,they should be classified to the code of C26.9.In the process of coding,cod-ers should review case data thoroughly,enhance the accumulation of clinical knowledge,and strengthen communications with doc-tors,thereby enhancing coding precision.

Objective To detect the expression of vacuolar protein sorting-associated protein 33A(VPS33A)in the peripheral blood of elderly patients with pulmonary tuberculosis,and explore its correlation with clinical prognosis.Methods A total of 95 elderly pulmonary tuberculosis patients admitted to Macheng City People's Hospital from February 2019 to February 2021 were collected as the research group,and 90 healthy subjects in the same period were selected as control group.The expression of VPS33A and Toll like receptor 2(TLR2)in peripheral blood was detected by real-time fluorescent quantitative PCR(qRT-PCR),and the level of interleukin-6(IL-6)in peripheral blood was detected by enzyme-linked immunosorbent assay.Patients with pulmonary tuberculosis were given standardized anti-tuberculosis regimen therapy(2HRZE/4HR)treatment,and they were followed up for 12 months.According to their prognosis,they were divided into good prognosis group(n=58)and bad prognosis group(n=37).The predictive value of VPS33A for poor prognosis was analyzed by ROC curve.The correlation between serum VPS33A,IL-6 and TLR2 in poor prognosis group was analyzed by Pearson method.Logistic regression analysis was used to explore the factors influencing poor prognosis in elderly patients with pulmonary tuberculosis.Results Compared with the control group,VPS33A level(0.87±0.22 vs 1.02±0.23)in peripheral blood was lower,but IL-6(22.13±5.36 pg/ml vs 18.53±4.68 pg/ml)and TLR2 levels(1.26±0.25 vs 0.99±0.21)were higher in the pre-treatment study group,with significant differences(t=6.170,6.682,11.241,all P＜0.05).Compared with the pre-treatment study group,VPS33A level(0.95±0.25)in peripheral blood was higher,but IL-6(19.66±5.44 pg/ml)and TLR2 levels(1.11±0.2)were lower in the post-treatment study group,with significant differences(t=3.336,4.648,6.331,all P＜0.05).The level of VPS33A(0.71±0.16)in peripheral blood of poor prognosis group was lower than that of good prognosis group(0.97±0.22),while the levels of IL-6(26.41±7.16 pg/ml)and TLR2(1.35±0.26)were higher than those of good prognosis group(19.40±4.21pg/ml,1.20±0.24),with significant differences(t=5.555,6.012,2.875,all P＜0.05).Pearson correlation analysis showed that VPS33A in the pre-treatment study group was negatively correlated with IL-6 and TLR2 levels(r=-0.649,-0.634,all P＜0.05).ROC curve analysis results showed that the AUCs of VPS33A,IL-6 and TLR2 for predicting the prognosis of tuberculosis in the elderly were 0.805,0.842 and 0.882,respectively.The combined AUC of the three was 0.971,which was higher than that predicted by the three alone(Z=4.010,3.136,2.285,P=0.001,0.002,0.022).Logistic regression analysis showed that VPS33A,IL-6 and TLR2 were the influencing factors for poor prognosis of elderly pulmonary tuberculosis patients(all P＜0.05).Conclusion The expression of VPS33A is down-regulated in the peripheral blood of elderly patients with pulmonary tuberculosis,which may be a good predictive value for the prognosis of elderly patients with pulmonary tuberculosis,and be a factor affecting bad prognosis.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Background::Despite the adverse effects of ambient fine particulate matter (PM 2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM 2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods::In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long-term PM 2.5 exposure was calculated using 1-km resolution satellite-based PM 2.5 estimates. PM 2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort-stratified Cox proportional hazards models, individually and in combination. Results::In 488,166 person-years of follow-up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM 2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM 2.5 stratification (≤65.02 μg/m 3) other than in high PM 2.5 stratification (>65.02 μg/m 3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66-0.85) and 1.10 (95% CI: 0.99-1.22), respectively. Similar results were observed for PA intensity. High PM 2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR= 1.79, 95% CI: 1.59-2.01 for PA volume; HR = 1.82, 95% CI: 1.64-2.02 for PA intensity). Conclusion::PA could reduce type 2 diabetes risk in low-pollution areas, but high PM 2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long-term polluted residents.