[Kaixinsan alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex].

OBJECTIVE: To investigate the effect of Kaixinsan (KXS, a traditional Chinese medicine formula) for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism. METHODS: Forty female BALB/c mice were randomized equally into control group, model group, and low- and high-dose KXS treatment groups, and in the latter 3 groups, mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage. Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test, and the changes in serum levels of depression-related factors were examined. RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS. The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control. RESULTS: KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models. RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress, lipid metabolism and iron ion binding in the prefrontal cortex. Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice. In SH-SY5Y cells, both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis. CONCLUSION: KXS alleviates adriamycininduced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Standardized IETA criteria enhance accuracy of junior and intermediate ultrasound radiologists in diagnosing malignant endometrial and intrauterine lesions.

OBJECTIVES: To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. METHODS: This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate-level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. RESULTS: Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver-operating-characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. CONCLUSIONS: The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate-level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Determining the optimal timing of adjuvant chemotherapy initiation after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: Studies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: This clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival. RESULTS: A total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001]. CONCLUSIONS: The optimal timing of AC initiation is ∼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.

Influence of the airflow and humidity on the chain aggregation during the film-formation in a flexible waterborne polyurethane formulation.

STATEMENT OF OBJECTIVES: Soft, waterborne polyurethane dispersions are indispensable components in many state-of-the-art materials, with applications ranging from binders for coatings and adhesives to matrixes for flexible devices. While the static bulk nanostructure of such systems is widely studied, the influence that environmental conditions such as relative humidity and airflow have on their film formation and phase segregation behavior in supported films is unknown. EXPERIMENTS: Here, we elucidate the nanostructure evolution occurring during drying of an industrially relevant, soft polyurethane, utilizing real-time, non-destructive grazing incidence X-ray scattering analysis. Using an environmental-controlled casting cell, we highlight the differences between the drying mechanism under different conditions generated by tuning the airflow and the relative humidity. FINDINGS: Our results show how the environment's relative humidity strongly influences chain aggregation and chain interdiffusion due to extended plasticization of the hard segment at high humidities, while accelerated air flows are responsible for the occurrence of (partial) skinning. Interestingly, despite changes in the chain aggregation behavior and occurrence of skinning and skin breakup during drying resulting in higher roughness at the film surface, minor influence is registered on the bulk tensile properties of the films, revealing the resilient nature towards environmental conditions of these soft weakly phase segregating polyurethane systems.

Organ-specific Biodosimetry Modeling Using Proteomic Biomarkers of Radiation Exposure.

In future mass casualty medical management scenarios involving radiation injury, medical diagnostics to both identify those who have been exposed and the level of exposure will be needed. As almost all exposures in the field are heterogeneous, determination of degree of exposure and which vital organs have been exposed will be essential for effective medical management. In the current study we sought to characterize novel proteomic biomarkers of radiation exposure and develop exposure and dose prediction algorithms for a variety of exposure paradigms to include uniform total-body exposures, and organ-specific partial-body exposures to only the brain, only the gut and only the lung. C57BL6 female mice received a single total-body irradiation (TBI) of 2, 4 or 8 Gy, 2 and 8 Gy for lung or gut exposures, and 2, 8 or 16 Gy for exposure to only the brain. Plasma was then screened using the SomaScan v4.1 assay for ∼7,000 protein analytes. A subset panel of protein biomarkers demonstrating significant (FDR<0.05 and |logFC|>0.2) changes in expression after radiation exposure was characterized. All proteins were used for feature selection to build 7 different predictive models of radiation exposure using different sample cohort combinations. These models were structured according to practical field considerations to differentiate level of exposure, in addition to identification of organ-specific exposures. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. The overall predictive accuracy for all models was 100% at the model training level. When tested with reserved samples Model 1 which compared an "exposure" group inclusive of all TBI and organ-specific partial-body exposures in the study vs. control, and Model 2 which differentiated between control, TBI and partials (all organ-specific partial-body exposures) the resulting prediction accuracy was 92.3% and 95.4%, respectively. For identification of organ-specific exposures vs. control, Model 3 (only brain), Model 4 (only gut) and Model 5 (only lung) were developed with predictive accuracies of 78.3%, 88.9% and 94.4%, respectively. Finally, for Models 6 and 7, which differentiated between TBI and separate organ-specific partial-body cohorts, the testing predictive accuracy was 83.1% and 92.3%, respectively. These models represent novel predictive panels of radiation responsive proteomic biomarkers and illustrate the feasibility of development of biodosimetry algorithms with utility for simultaneous classification of total-body, partial-body and organ-specific radiation exposures.

[Skin disease caused by Mycobacterium marinum:a case report].

Mycobacterium marinum infection often affects the extremities, causing single or multiple skin lesions. With the improvement of molecular detection technology and the clinical application of NGS pathogen detection, the diagnosis rate of Mycobacterium marinum skin disease is gradually increasing. This article reported the case of a 54-year-old man who was stung by a marine fish and gradually developed swelling and nodules on his right hand and right upper limb. He was diagnosed with Mycobacterium marinum infection by detection of the tuberculosis resistance gene dissolution curve of the pus and the identification of the bacteria. Oral rifampicin combined with clarithromycin and minocycline was given for anti-infection treatment. During follow-up, the abscesses and nodules gradually shrank and eventually disappeared. By presenting the diagnosis and treatment of this case, the understanding of this disease among clinicians can be improved to avoid misdiagnosis and missed diagnosis.

[Super minimally invasive surgery changing the treatment paradigm for rectal cancer].

The treatment mode for patients with low rectal cancer (LRC) is still mainly surgical treatment. With the advancement of medical technology, the current surgical mode is more inclined towards super minimally invasive surgery (SMIS) that preserves organs and functions. SMIS belongs to organ preservation surgery, including non-full thickness and full-thickness resection under digestive endoscopy, laparoscopic or robotic full-thickness resection, and transanal minimally invasive surgery, which can cover all stages of TNM staging. The paper elaborates on the importance of preoperative accurate diagnosis and risk stratification in selecting appropriate SMIS methods, the new progress of imaging technology in accurately predicting lymph node metastasis, providing preoperative TNM staging and risk stratification, and guiding SMIS treatment. Finally, the paper introduces the SMIS surgical options for the treatment of LRC that have been developed and are currently in the clinical research stage, with the aim of maximizing the quality of life for LRC patients.

[The development, implementation principles and application of the endoscopic super minimally invasive surgery].

Endoscopic therapy has gone through three stages of development: intraluminal treatment, endoscopic tunneling technology, and endoscopic super minimally invasive surgery (ESMIS). Compared to the drawbacks of traditional surgical methods"organ resection and anatomical reconstruction", super minimally invasive surgery (SMIS) emphasizes the surgical concept of"curing diseases while preserving organs and functions". SMIS conducts treatment through four channels: natural cavity channel, tunnel channel, puncture channel, and multi cavity channel. It offers dozens of surgical methods for diagnosing and treating gastrointestinal diseases. At present, relatively sound implementation principles for ESMIS treatment have been established to ensure the safety and effectiveness of surgery, and to continuously expand other diagnostic and therapeutic fields.

[Effect of Da Vinci robotic transanal minimally invasive surgery for rectal neoplasms].

Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.

[Clinical characteristics of appendix orifice polyps and the effect endoscopic super minimally invasive treatment].

To analyze the clinical characteristics of appendiceal orifice polyps and the effect of endoscopic super minimally invasive treatment. A retrospective analysis was conducted on the general situation (age and sex), the classification of appendiceal orifice polyps, the treatment method under endoscope, postoperative pathology and postoperative complications in patients who underwent resection of appendiceal orifice polyps at the Peking University First Hospital and the First Medical Center of the PLA General Hospital from January 1, 2022, to December 31, 2023. A total of 47 patients were included, consisting of 28 males and 19 females, with 35-86 (61±12) years. Appendiceal orifice polyps were classified into four types: type 0 (14 cases), type 1 (15 cases), type 2 (12 cases), and type 3 (6 cases). Among the endoscopic morphologies, 22 cases were granular laterally spreading tumors. Endoscopic mucosal dissection was performed in 37 cases. Postoperative appendiceal stent placement was performed in 1 case. The pathological types of polyps included adenoma in 15 cases, high-grade intraepithelial neoplasia in 10 cases, intramucosal carcinoma in 4 cases, submucosal carcinoma in 5 cases, inflammatory polyps in 1 cases, and sessile serrated lesion in 12 cases. Curative resection was performed in 44 cases. There were no postoperative complications such as bleeding, perforation, or acute appendicitis. The pathology of appendiceal polyps is mostly precancerous lesions, and the treatment scheme of endoscopic super minimally invasive resection is both safe and effective.

Short-term effects of air pollutants and meteorological factors on outpatients with allergic airway disease in Ningbo, China, 2015-2021.

OBJECTIVES: The allergic airway disease, such as allergic rhinitis, chronic rhinosinusitis, asthma, is a general term of a range of inflammatory disorders affecting the upper and lower airways and lung parenchyma. This study aimed to investigate the short-term effects of air pollutants and meteorological factors on AAD-related daily outpatient visits. STUDY DESIGN: An ecological study. METHODS: Data on outpatient visits due to AAD (n = 4,554,404) were collected from the platform of the Ningbo Health Information from January 1, 2015 to December 31, 2021. A Quasi-Poisson generalized additive regression model was established to analyze the lag effects of air pollution on daily outpatient visits for AAD. Restricted cubic spline functions were used to explore the potential non-linear relationships between air pollutants and meteorological and daily outpatient visits for AAD. RESULTS: PM2.5, PM10, SO2, NO2, or CO were associated with daily outpatient visits for AAD, and there was a significant increasing trend in the cumulative lag effects. SO2 had the largest effect at Lag07, with a 25.3% (95% CI: 21.6%-29.0%) increase in AAD for every 10 µg/m3 increase in exposure concentration. Subgroup analysis showed that the 0-18 years old age group had the strongest effects, especially for AR, and all effects were stronger in the cold season. CONCLUSIONS: Given that patients aged 0-18 are more susceptible to environmental changes, protective measures specifically for children should be taken during dry and cold weather conditions with poor air quality.

[Detection of colorectal advanced neoplasms among the cancer screening population in urban areas of Henan Province and analysis on its influencing factors].

Objective: To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors. Methods: A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results: A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio (OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion: The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.

Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network.

PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

[Outcomes of total knee arthroplasty combined with the modified "overlap" technique in the treatment of knee osteoarthritis with permanent patellar dislocation].

Objective: To investigate the clinical outcomes of total knee arthroplasty (TKA) combined with the modified "overlap" technique in the treatment of end-stage knee osteoarthritis with fixed patellar dislocation. Methods: This is a retrospective case series study. Clinical data of 19 patients (22 knees) who underwent TKA combined with the modified "overlap" technique for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation from January 2011 to January 2022 in the Department of Orthopaedics, the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. The cohort included 5 males (6 knees) and 14 females (16 knees), with an age of (60.6±12.2) years (range:33 to 77 years) and a body mass index of (25.4±4.1) kg/m² (range:20.0 to 33.0 kg/m²). Among them, 11 cases (12 knee) had valgus deformity, with Keblish classification showing mild in 2 cases (2 knees), moderate in 6 cases (6 knees), and severe in 4 cases (4 knees). All cases were treated using a medial parapatellar approach, with lateral retinaculum release combined with the "overlap" technique to restore the patellar trajectory. Knee function was evaluated using the American Knee Society (KSS) Score. Paired sample t tests were used for intergroup comparisons. Results: All patients successfully completed the surgery. Postoperatively, patellar dislocation, knee valgus deformity, flexion contracture deformity, and extensor lag were all corrected. All patients were followed up, with a follow-up duration of (63.8±35.2) months (range:24 to 136 months). One patient experienced periprosthetic infection 2 weeks postoperatively, 1 patient had recurrent patellar dislocation 2 months postoperatively, 1 patient developed knee stiffness 3 months postoperatively and underwent closed manipulation. No other patients exhibited signs of patellar dislocation or subluxation. At the last follow-up, the KSS clinical score improved from (36.4±12.7) points preoperatively to (83.4±6.3) points postoperatively (t=-15.15, P<0.01), and the KSS functional score improved from (30.7±11.1) points preoperatively to (77.6±8.3) points postoperatively (t=-14.37, P<0.01). The range of motion of the knee increased from 81.7°±19.6° preoperatively to 107.6°±12.5° postoperatively (t=-4.85, P<0.01). Conclusion: TKA combined with the modified "overlap" technique is an effective surgical option for the treatment of end-stage knee osteoarthritis with permanent patellar dislocation, demonstrating satisfactory clinical outcomes.

Stringent Tests of Lorentz Invariance Violation from LHAASO Observations of GRB 221009A.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

[Clinical characteristics analysis of 4 cases with acute flaccid myelitis in children].

Objective: To summarize the clinical manifestations, diagnosis, treatment and prognosis of acute flaccid myelitis (AFM) in children. Methods: Clinical characteristics of 4 AFM cases from Department of Neurology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from September 2018 to November 2022, were analyzed retrospectively. Results: The age of 4 children with AFM was 7 years, 4 years and 3 months, 7 years and 1 month, 6 years and 5 months, respectively. There were 2 boys and 2 girls. Prodromal infection status showed 3 children of respiratory tract infection and 1 child of digestive tract infection. The main manifestation was asymmetrical limb weakness after infection, and the affected limb range was from monoplegia to quadriplegia. Cranial nerve injury was involved in 1 child, no encephalopathy. Magnetic resonance imaging in the spinal cord of all 4 children showed long T1 and T2 signals, mainly involving gray matter. Cerebrospinal fluid cell-protein separation was observed in 2 children. Pathogen detected in 1 child pharyngeal swab was enterovirus D68. Antibody IgM to adenovirus was positive in the blood of 1 child. Antibody IgG against Echo and Coxsackie B virus were positive in the blood of another child. After glucocorticoid, human immunoglobulin or simple symptomatic treatment and at the same time under later rehabilitation training, muscle strength recovered to different degrees, but there were disabilities left in 3 children. Conclusions: AFM should be considered in children with acute and asymmetrical flaccid paralysis accompanied by abnormal magnetic resonance imaging signal in the central region of spinal cord, especially post-infection. The effective treatment is limited and the prognosis is poor.

[Application of 21-gene recurrence risk score in patients with breast cancer].

Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

[Calenduloside E inhibits hepatocellular carcinoma cell proliferation and migration by down-regulating GPX4 and SLC7A11 expression through the autophagy pathway].

OBJECTIVE: To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma (HCC) cell proliferation and migration. METHODS: HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4, SLC7A11, LC3, P62 and phosphorylation of Akt/mTOR using Western blotting. The effects LY294002 and Rapamycin (the inhibitor and activator of autophagy, respectively) on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays. The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes. GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting. RESULTS: Calenduloside E obviously inhibited the viability of HCC cells. GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines, and their expression levels were negatively correlated with the patients'survival. In HCC cell lines, calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins, activated the Akt-mTOR pathway, and enhanced the expression of LC3 Ⅱ. The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002. Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells, while activating this pathway produced the opposite effect. CONCLUSION: Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.