ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Squamous Cell/virology* ; Human Papillomavirus Viruses/isolation & purification* ; Margins of Excision ; Oropharyngeal Neoplasms/virology* ; Papillomavirus Infections/virology* ; Prognosis ; Prospective Studies ; Robotic Surgical Procedures/methods*

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To compare the short-term efficacy between proximal femoral bionic nails (PFBN) and 3G Gamma nails in the fixation intertrochanteric femoral fractures in the elderly.Methods:A retrospective study was conducted to analyze the data of 78 elderly patients with intertrochanteric femoral fracture who had been admitted to Department of Trauma Surgery, The Hospital Affiliated to Qingdao University from October 2021 to December 2022. There were 35 males and 43 females with an age of (76.0±7.9) years. By Evans classification: 6 cases of type Ⅰ, 21 cases of type Ⅱ, 24 cases of type Ⅲ, 23 cases of type Ⅳ, and 4 cases of type Ⅴ. The patients were divided into 2 groups according to their internal fixation methods: a PFBN group of 35 patients fixed by PFBN and a Gamma group of 43 cases fixed with 3D Gamma nails. The time from injury to operation, hospital stay, operation time, intraoperative blood loss, weight-bearing time, fracture healing time, and Harris hip score, visual analogue scale (VAS) and incidence of complications at 6 months after operation were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (14.0±4.0) months. There were no significant differences between the PFBN and Gamma groups in operation time [(58.9±8.2) min versus (58.1±6.8) min], intraoperative blood loss [(138.0±24.9) mL versus(126.8±25.7) mL], hospital stay [(10.9±2.9) d versus (10.3±4.0) d],fracture healing time [(5.0±1.3) months versus (5.1±1.3) months], or good and excellent rate by the Harris hip score [82.9% (29/35) versus 76.7% (33/43)], VAS score [0(0, 1) points versus 1(0, 1) points], or incidence of complications at 6 months after operation [2.9% (1/35) versus 4.7% (2/43)] (all P>0.05). However, the complete weight-bearing time for the PFBN group was (5.3±1.2) weeks, significantly earlier than that for the Gamma group [(6.9±1.4) weeks] ( P<0.05). Conclusion:In the fixation of intertrochanteric femoral fractures in the elderly patients, both PFBN and 3D Gamma nails can achieve satisfactory short-term efficacy, but PFBN is more beneficial to the functional recovery of the hip joint because it leads to earlier complete weight-bearing time than 3D Gamma nails.

Objective To explore the prognostic value of hs-cTnⅠ in patients with suspected acute coronary syndrome(ACS)in emergency department.Methods A large-scale,prospective observa-tional study was conducted on totally 966 patients with suspected ACS admitted in Fuwai Hospi-tal from January 2017 to October 2020.Their baseline serum/plasma hs-cTnⅠ level was detected at admission,conventional treatment was performed,and relevant data were collected.Logistic regression analysis was used to predict the risk of primary and secondary endpoint events within 30 d by hs-TnⅠ concentration,and subgroup analysis was performed.Results Among the 966 patients,the time from chest pain to visit was 5.0(2.5,13.0)h,and 284 patients had primary end-point events within 30 d,including 283 cases of myocardial infarction(99.6％)at the first visit,1 case of recurrent myocardial infarction(0.4％),5 cases of cardiovascular death(1.8％),and 1 case of unplanned revascularization(0.4％).When hs-cTnⅠ was at the minimum detection limit of 2 ng/L,the incidence of adverse events was 5.8％,when the limit of 70 ng/L,the incidence was 49.2％,and when of 316 ng/L,the incidence reached 100％.The model could correctly classify 92.3％of the patients.Conclusion The hs-cTn sequence has a good predictive effect for the risk of short-term cardiovascular adverse events in Chinese population.

Objective:To investigate the recent epidemic trends and spatiotemporal distribution characteristics of gonorrhea in China, and to provide a reference for precise prevention and control of gonorrhea.Methods:Data on reported cases of gonorrhea in China (not including Hongkong, Macau and Taiwan regions of China) were collected from the Infectious Diseases Surveillance System of Chinese Disease Prevention and Control Information System from 2018 to 2023. The trends in reported incidence rates of gonorrhea in China were analyzed using the Joinpoint regression model. Global spatial autocorrelation analysis with the Moran's index and global G-statistic, as well as local spatial autocorrelation analysis, were employed to explore the clustering patterns and hotspot regions of gonorrhea at the county level. In the spatiotemporal scanning analysis, a Poisson distribution model was employed to identify clusters of gonorrhea cases.Results:The reported incidence rates of gonorrhea in China decreased from 9.59 per 100 000 in 2018 to 7.35 per 100 000 in 2023, with an average annual percent change of -4.9%, but this decreasing trend was not statistically significant ( P = 0.11). The reported incidence rates of gonorrhea at the county level in China exhibited a significant positive global spatial autocorrelation, with the global Moran's indices ranging from 0.39 to 0.60 (all P < 0.001) ; the Getis-Ord general G test statistic Z (G) values were all greater than 1.96, indicating a high-value clustering pattern of gonorrhea cases. The local spatial autocorrelation analysis showed that hotspot regions were predominantly distributed in southeastern coastal areas and southwestern China. A total of 70 clusters were identified through the spatiotemporal scanning analysis, and mainly located in southeastern coastal areas and southwestern China. Conclusions:In recent 6 years, the overall reported incidence rates of gonorrhea in China showed a fluctuating decline; there was a significant spatiotemporal clustering characteristic with regard to gonorrhea epidemic at the county level in China, and the hotspot regions were basically consistent with the spatiotemporal clusters, which were mainly distributed in southeastern coastal areas and southwestern China. Further investigation into the causes and precise prevention and control measures are needed.

Objective:To investigate the epidemiological trends and spatio-temporal distribution characteristics of syphilis in China from 2010 to 2023.Methods:Data on syphilis cases reported from 31 provinces, autonomous regions or municipalities from 2010 to 2023 were collected from the Infectious Diseases Surveillance System of Chinese Disease Prevention and Control Information System. Joinpoint 5.2.0 software was used to analyze the epidemiological trends of syphilis, ArcGIS 10.5 software was used for spatial autocorrelation analysis at the county level, and SaTScan 10.2.3 software was used for space-time scan analysis.Results:The national reported incidence rates of syphilis increased from 26.86 per 100 000 in 2010 to 37.60 per 100 000 in 2023, with an average annual percent change of 1.82% (95% CI: 0.81% - 2.89%), and the upward trend in the reported incidence rates was statistically significant ( P = 0.002). There was a positive spatial autocorrelation in the reported incidence rates of syphilis at the county level in China (Moran's Ⅰ range: 0.47 - 0.60, all P < 0.001), and all of the Getis-Ord general test statistic Z (G) values were > 1.96, indicating a high-value clustering pattern in the reported incidence rates of syphilis. The local spatial autocorrelation analysis showed that the annual number of hotspot areas ranged from 180 to 294, which were mainly located in Xinjiang, Qinghai, Guizhou, Sichuan and Yunnan. A total of 92 spatio-temporal clusters were identified by space-time scan analysis, which were mainly distributed in Zhejiang, Guangxi, Guangdong and Fujian from 2010 to 2012, in Xinjiang from 2013 to 2017, and in Sichuan, Guizhou, Chongqing, etc., from 2019 to 2023. Conclusions:From 2010 to 2023, the reported incidence rates of syphilis in China exhibited a fluctuating increase on the whole, with obvious spatio-temporal clustering characteristics. The hotspot areas were basically consistent with the spatio-temporal clusters, and were mainly distributed in the northwestern, southeastern coastal and southwestern areas. Over time, the spatio-temporal clusters gradually changed from the southeast coastal and northwestern areas to the southwestern areas.