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Lijing Huo,1 Xuexin Liu,2 Changmei Wei,1 Fang Yu,1 Luping Ren,3 Yanqing Tie1 1Department of Medical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 2Health Check-up Centers, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Lijing Huo, Department of Medical Laboratory, Hebei General Hospital, 348 Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, People’s Republic of China, Email huolijing1979@126.comAim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations.Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations.Results: We found that gender were associated with 25(OH)D, OC, β-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P< 0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in β- CTX levels between seasons.Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.Keywords: 25-hydroxyvitamin D, 25(OH)D, osteocalcin, OC, β-carboxy-terminal cross-linking telopeptide of type I collagen, β-CTX, N-terminal procollagen of type I collagen, P1NP, parathyroid hormone 1-84, PTH1-84

Jialin Ma, Xiaojing Liu, Yongxin Li Faculty of Education, Henan University, Kaifeng, Henan Province, People’s Republic of ChinaCorrespondence: Yongxin Li, Faculty of Education, Henan University, Kaifeng, Henan Province, 475000, People’s Republic of China, Tel +8613503780519, Email liyongxin@henu.edu.cnBackground: Studies have shown that elderly individuals have significantly worse facial expression recognition scores than young adults. Some have suggested that this difference is due to perceptual degradation, while others suggest it is due to decreased attention of elderly individuals to the most informative regions of the face.Methods: To resolve this controversy, this study recruited 85 participants and used a behavioral task and eye-tracking techniques (EyeLink 1000 Plus eye tracker). It adopted the “study-recognition” paradigm, and a mixed experimental design of 3 (facial expressions: positive, neutral, negative) × 2 (subjects’ age: young, old) × 3 (facial areas of interest: eyes, nose, and mouth) was used to explore whether there was perceptual degradation in older people’s attention to facial expressions and investigate the differences in diagnostic areas between young and older people.Results: The behavioral results revealed that young participants had significantly higher facial expression recognition scores than older participants did; moreover, the eye-tracking results revealed that younger people generally fixated on faces significantly more than elderly people, demonstrating the perceptual degradation in elderly people. Young people primarily look at the eyes, followed by the nose and, finally, the mouth when examining facial expressions. The elderly participants primarily focus on the eyes, followed by the mouth and then the nose.Conclusion: The findings confirmed that young participants have better facial expression recognition performance than elderly participants, which may be related more to perceptual degradation than to decreased attention to informative areas of the face. For elderly people, the duration of gaze toward the facial diagnosis area (such as the eyes) should be increased when recognizing faces to compensate for the disadvantage of decreased facial recognition performance caused by perceptual aging.Keywords: facial expressions, age, areas of interest, eye movement

Yan Tang,1,&ast; Xiaoling Liu,1,&ast; Wang Zhou,2 Xiachuan Qin3 1Department of Ultrasound, Beijing Anzhen Hospital Nanchong Hospital, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, 637000, People’s Republic of China; 2Department of Ultrasound, The First Affiliated hospital of Anhui medical University, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Ultrasound, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiachuan Qin, Department of Ultrasound,Chengdu Second People’s Hospital,Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18113917878, Email 11326636@qq.comPurpose: To assess the crescentic status of IgA nephropathy (IgAN) non-invasively using a superb microvascular imaging (SMI)-based radiomics machine learning (ML) model.Patients and Methods: IgAN patients who underwent renal biopsy from June 2022 to October 2023, with two-dimensional ultrasound (US) and SMI examinations conducted one day prior to the renal biopsy. The patients selected were divided randomly into a training group and a test group in a 7:3 ratio. Radiomic features were extracted from US and SMI images, then radiomic features were constructed and ML models were further established using logistic regression (LR) and extreme gradient boosting (XGBoost)XGBoost to determine the crescentic status. The utility of the proposed model was evaluated using receiver operating characteristics, calibration, and decision curve analysis. The SHapley Additive exPlanations (SHAP) was utilized to explain the best-performing ML model.Results: A total of 147 IgAN patients were included in the study, with 103 in the training group and 44 in the test group .Among them, the US-SMI based XGBoost model achieved the best results, with an the area under the curve (AUC) of 0.839 (95% CI,0.756– 0.910) and an accuracy of 78.6% in the training group.In the test group, the AUC was 0.859 (95% CI,0.721– 0.964), and the accuracy was 81.8%, significantly surpassing the ML model of a single modality and the clinical model established based on occult blood. Additionally, the decision curve analysis (DCA) demonstrated that the XGBoost model provided a higher overall net benefit in the both groups.Conclusion: The SMI radiomics ML model has the capability to accurately predict the crescentic status of IgAN patients, providing effective assistance for clinical treatment decisions.Keywords: IgA nephropathy, crescent, ultrasound, superb microvascular imaging, radiomics

Chuanjiang Dong,1,&ast; Yueqing Wang,2,3,&ast; Yi Cai,4,&ast; Yuhuang Wu,2,3 Wei Chen,2,3 Lu Wang,2,3 Xiaowen Liu,2 Lili Zou,2,3 Jun Wang5 1Department of Urology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong province, 523718, People’s Republic of China; 2Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 3Yichang Key Laboratory of Infection and Inflammation, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 4Department of Laboratory Medicine, Xiaogan Central Hospital, Xiaogan, Hubei Province, 432099, People’s Republic of China; 5The Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Zou; Jun Wang, Email zoulili@ctgu.edu.cn; wangjfox@ctgu.edu.cnPurpose: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs.Methods: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model.Results: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity.Conclusion: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.Keywords: Ebselen, antibiotic adjuvant, thioredoxin reductase, reactive oxygen species

Hanzhi Chen,1,&ast; Leting Zhou,1,&ast; Meilin Yan,1,&ast; Cheng Li,1 Bin Liu,1 Xiaobin Liu,1 Weiwei Shan,1 Ya Guo,2 Zhijian Zhang,1 Liang Wang1 1Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Key Laboratory of Advanced Process Control for Light Industry (Ministry of Education), Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Zhang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email zzjwxyy@163.com Liang Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangliang_wuxi@126.comBackground: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health.Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients.Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical–bioelectrical records, were used for model validation.Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women.Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.Keywords: serological test results, cellular bioelectrical indicators, machine learning, End-stage kidney disease

Zonglin Li,1,&ast; Xingming Shu,1,&ast; Xin Liu,1 Qiuyun Li,2 Yifu Hu,2 Bingbing Jia,2 Min Song3 1Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Grade 2023, Clinical Medicine College, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Song, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +8615883059785, Email songminlele2007@126.comAbstract: Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.Keywords: gastric cancer, chemoresistance, cellular mechanisms, molecular mechanisms

Xueen Liu,1 Fang Pan,1 Qingmei Wang,1 Shuai Wang,1 Jiale Zhang2 1Department of Nursing, Beijing Hepingli Hospital, Beijing, People’s Republic of China; 2Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiale Zhang, Email zhang_tcm@163.comAbstract: Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.Keywords: traditional Chinese rehabilitation exercise, pain, myofascial chain, rehabilitation

Jian Jiang,1,2,&ast; Xiaoyan Hou,1,&ast; Lili Gu,3 Xian Liu,1 Huiting Lv,1 Jiaxin Xiong,1 Hongmei Kuang,1,2 Xiaofeng Jiang,1 Shunda Hong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Hong, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88693825, Email dyfy05441@ncu.edu.cnPurpose: This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN).Patients and Methods: Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas.Results: Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and decreased short-range FCD in the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and precuneus. However, there was no significant difference in either long-range or short-range FCD between the PHN and HZ patients. Long-range FCD deficit areas and the right insula showed altered functional connectivity in PHN patients. Furthermore, pain duration in patients with PHN was correlated with abnormal long-range FCD.Conclusion: Herpes zoster pain widely affects intra- and inter-regional functional connectivity, leading to disrupted short-range FCD and increased long-range FCD during different stages of the disease. Long-term chronic pain in PHN patients may impair the pain emotion regulation pathway. These findings could improve our understanding of the pathophysiological mechanisms of HZ and PHN and offer neuroimaging markers for HZ and PHN.Keywords: functional connectivity density, herpes zoster, postherpetic neuralgia, pain, functional magnetic resonance imaging

Jingfei Weng,1,2,&ast; Yuyao Xiao,1,&ast; Jing Liu,3,&ast; Xiaohua Liu,4 Yuqing He,2 Fei Wu,1 Xiaoyan Ni,1 Chun Yang1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang; Xiaoyan Ni, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 18702135336 ; +86 15201803582, Email dryangchun@hotmail.com; nixiaoyan1103@126.comPurpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student’s t test, χ 2 test, and multivariable regression analysis.Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson–Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.Keywords: liver neoplasms, magnetic resonance imaging, P53-mutated

Jian Li,1,&ast; Li Liu,2,&ast; Zhiyun Gao,1 Xia Chuai,3 Xiaokun Liu,4 Xiaobo Zhang,2 Xinyu Zhang,2 Xiaoqing Su,2 Qian Xu,2 Zhuojun Deng2 1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega Science, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuojun Deng, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email dengzhuojun@126.com; 37700469@hebmu.edu.cnPurpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China’s Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology.Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS.Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment.Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.Plain Language Summary: Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS. Keywords: visceral leishmaniasis, metagenomic second-generation sequencing, bronchoalveolar lavage fluid, parasite diseases, case report

Xiaoming Liu,1 Xiaoni Yang2 1Department of Geriatric Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of ChinaCorrespondence: Xiaoni Yang, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email yangxiaoni1979@163.comAbstract: Global aging is rapidly accelerating, which significantly influences the health systems worldwide. Frailty emerges as the most conspicuous hallmark of aging, imposing novel global health challenges. Characterized by a multifaceted decline across physiological system, frailty diminishes an individual’s capacity to maintain equilibrium in the presence of stressors, which leads to adverse outcomes such as falls, delirium, and disability. Several screening tools and interventions have been developed to mitigate the harm caused by frailty to human health, but research on frailty in mainland China commences belatedly with scant studies conducted. Therefore, it is imperative to explore screening methods and treatment modalities tailored to the Chinese context, thereby enhancing the older adults’ quality of life and advancing social medicine. This review aims to elucidate the evolution, diagnosis, and management of frailty, alongside the challenges it poses, with the overarching goal of guiding future diagnostic and therapeutic endeavors. Specifically, we summarized the mechanisms of frailty and intervention strategies in elderly people, and meanwhile, we evaluated the advantages and disadvantages of different measurement tools.Keywords: frailty, geriatrics, pathogenesis, assessment, intervention

Yanyan Song, Bin Zhang, Xudong Liu Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Xudong Liu, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqnfective shoingDistrict, Yinchuan, 750004, People’s Republic of China, Tel +869516743014, Fax +86 0951-6744302, Email xudong669@163.comObjective: To summarize the experience of surgical treatment and perioperative management of a case of infective endocarditis with aortic valve damage in a child with congenital heart disease.Methods: We retrospectively analyzed the treatment of a pediatric patient with infective endocarditis combined with aortic valve damage, who was admitted to the Department of Cardiovascular Surgery of our hospital in Yinchuan in March 2024. We summarize the case data and present a literature review.Results: The child recovered well after surgery, with echocardiographic re-examination, mild regurgitation of the aortic valve, and no recurrence of endocarditis. She recovered and was discharged from hospital.Conclusion: The surgical treatment of infective endocarditis in children has achieved satisfactory results, and the timing of and indications for surgery are very important to achieve the therapeutic effect.Keywords: infective endocarditis, congenital heart disease, cardiac surgical procedures, child

Xiao-Meng Xie,1 Sha Sha,1 Hong Cai,2 Xinyu Liu,1 Isadora Jiang,3 Ling Zhang,1 Gang Wang1 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 2Unit of Medical Psychology and Behavior Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Bellarmine College of Liberal Arts, Loyola Marymount University, Los Angeles, CA, USACorrespondence: Gang Wang, Beijing Anding Hospital, Beijing, People’s Republic of China, Email gangwangdoc@gmail.comBackground: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals.Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated.Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05).Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.Keywords: major depressive disorder, MDD, EEG, alpha power, cognition impairment

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes

Shangyu Luo,1 Xueqin Hu,2 Yunjun Hong,1 Yunchun Gao,1 Xianglin Liu,1 Yu Peng,1 Xueqing Tong,3 Xiaobo Zhang,1 Jun Wen1 1Department of Neurology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 2Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 3Department of Brain Electrophysiology, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde City, Hunan Province, People’s Republic of ChinaCorrespondence: Xiaobo Zhang; Jun Wen, Fax +86 0736 7788009 ; +86 0736 7788010, Email 285058041@qq.com; cdwenjun1973@163.comPurpose: Research on post-stroke depression (PSD) following the lifting of coronavirus disease 2019 (COVID-19) restrictions remains sparse. This study aimed to investigate the factors associated with PSD after the easing of COVID-19 restriction measures.Patients and Methods: This cross-sectional study was conducted with 947 stroke patients (cerebral hemorrhage and cerebral infarction) meeting the inclusion criteria. Participants completed a demographic questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Additionally, data were collected on C-reactive protein (CRP), homocysteine (Hcy), modified Rankin Scale (mRS), stroke site, National Institutes of Health Stroke Scale (NIHSS), thyroid-stimulating hormone (TSH), and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. This study assessed correlations between these indices and PSD.Results: Stroke patients with a PHQ-9 score ≥ 5 were identified as having PSD, with a prevalence rate of 14.15%. No significant correlation was found between previous COVID-19 infection and PSD. However, multiple regression analysis revealed associations between PSD and the following factors: TSH (OR: 0.87, 95% CI: 0.76– 1), CRP levels (OR: 1.01, 95% CI: 1– 1.02), family history of stroke (OR: 4.25, 95% CI: 1.66– 10.88), migraine history (OR: 8.63, 95% CI: 2.49– 29.85), and shorter sleep duration (OR: 0.6, 95% CI: 0.51– 0.71) (all P

Lantian Xie,1,&ast; Yan Chen,1,&ast; Lifan Zhang,1– 3 Lidan Zhao,4 Tao Li,5 Xiaochun Shi,1,2 Xiaoqing Liu1– 3 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Email shixch7722@163.com; liuxq@pumch.cnObjective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients.Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI.Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment.Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients′ compliance with LTBI screening and TPT.Keywords: rheumatic diseases, latent tuberculosis infection, tuberculosis preventive treatment, knowledge, attitudes

Yuanchun Li,1,&ast; Zhengrong Yang,1,&ast; Qiping Ge,2 Yueqiu Zhang,1 Mengqiu Gao,2 Xiaoqing Liu,1,3,4 Lifan Zhang1,3,4 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lifan Zhang; Xiaoqing Liu, Email lifanzhang1982@126.com; liuxq@pumch.cnIntroduction: Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states.Methods: ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation.Results: Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p< 0.05), but no significant differences between the ATB group and the fever group. Stimulated with the four antigens, respectively, the cytokines, including IP-10Esat− 6, IP-10CFP− 10, IFN-γRv1733cSLP, IFN-γRv2028c, IL-6Esat− 6, IL-6Rv1733cSLP, IL-6Rv2028c, IL-2Rv1733cSLP, IL-2 Rv2028c, IL-1RaEsat− 6, IL-1RaCFP− 10, IL-1RaRv2028c, CXCL-1Esat− 6, CXCL-1CFP− 10, CXCL-1Rv1733cSLP, CXCL-1Rv2028c, MCP-1Esat− 6 and MCP-1CFP− 10, demonstrated accurate discrimination between ATB and LTBI (p< 0.05). Additive concentrations demonstrated significant secretion differences of IFN-γ, IP-10 and IL-2, primarily by virulence factors in ATB and latency-associated antigens in LTBI. Latency-associated antigens synergized with virulence factors, enhancing TH1-type cytokine diagnostic efficacy for discriminating ATB from LTBI, the AUC for TNF-α increased from 0.696 to 0.820 (p=0.038), IFN-γ increased from 0.806 to 0.962 (p=0.025), and IL-2 increased from 0.565 to 0.868 (p=0.007). Model selected by forward likelihood method indicated combined detection of IFN-γCFP− 10, IFN-γRv1733cSLP, IP-10Rv1733cSLP, and CXCL-1Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γCFP− 10 and IFN-γRv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943).Conclusion: Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.Keywords: active tuberculosis, cytokine, latent tuberculosis infection, latency-associated antigen, Mycobacterium tuberculosis, virulence factor

Yan Wang,1,2,&ast; Fengmei Li,1,2,&ast; Shanshan Wei,1,2,&ast; Wenqun Li,1,2 Junyong Wu,1,2 Shengnan Li,1,2 Xiongbin Hu,1,2 Tiantian Tang,1,2 Xinyi Liu1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institution of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-731-8529-2095, Email liuxinyi128@csu.edu.cnPurpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.Keywords: mitochondrial targeting, triphenylphosphonium cations, puerarin, ischemic myocardium-targeting peptide, liposomes

Biao Song,1– 3,&ast; Xiaohan Liu,1– 3,&ast; Hongzhong Jin1– 3 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhong Jin, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China, Email jinhongzhong@263.netAbstract: Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis, accounting for less than 3% of cases. It is characterized by widespread scaling and erythema that affects more than 90% of the body surface area. Alopecia can manifest as a symptom associated with the disease, further exacerbating the impact on the patient’s quality of life. We present the case of a patient with severe EP and diffuse alopecia who did not respond to conventional therapies. The patient was subsequently treated with ixekizumab as per labeled usage, resulting in complete resolution of both psoriatic skin lesions (Psoriasis area and severity index/PASI 100) and alopecia (The Severity of Alopecia Tool/SALT 0).Keywords: erythrodermic psoriasis, alopecia, ixekizumab

Hui Sun,&ast; Yan Liu,&ast; Ling Wang, Xiaoling Liu, WenHui Wang Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Wang; Xiaoling Liu, Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No. 1-1 Zhongfu Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 83626512, Email liuxiaoling15l@163.comObjective: Accurate diagnosis is very important to block the transmission of tuberculosis. The quality of sputum culture affects the diagnostic accuracy. The quality of sputum samples is not optimistic. Therefore, this study investigated whether health care failure mode and effect analysis (HFMEA) can improve specimen quality and detection efficiency in sputum specimen management in tuberculosis departments.Methods: This study is a non-randomized controlled trial study. A convenience sampling method was used to select 110 patients who visited the Department of Tuberculosis of the Second Hospital of Nanjing from September to November 2022 and December 2022 to February 2023 as the control group and the experimental group. Control groups followed standard operating procedures for sputum specimen collection. In the experimental group, HFMEA model was used to control the quality on this basis. After 3 months of intervention, the qualified rate and positive detection rate of sputum samples were compared between the two groups.Results: A total of 634 sputum specimens were included in the experimental group and 647 in the control group. Compared with the control group, the qualification rate of sputum specimens was higher in the experimental group (84.54% vs 79.13%); the positive detection rates of the X-Pert assay (27.88% vs 16.19%), sputum culture (20.29% vs 12.68%), and sputum smear (22.29% vs 15.81%) were all higher in the experimental group (all P < 0.05). Patients in the experimental group had higher knowledge mastery and nurse sputum sample management scores (P < 0.05). However, patient satisfaction with sputum specimen management in the experimental group was lower than in the control group (7.72 ± 0.74 vs 8.38 ± 0.85, P < 0.001).Conclusion: The application of the HFMEA model in sputum specimen management can effectively improve specimen quality and positive detection rates.Keywords: healthcare failure mode and effect analysis (HFMEA), tuberculosis, sputum, nursing care, risk management

Jiangming Yu,1 Zhengguang Xiao,2 Ronghua Yu,1 Xiaoming Liu,1 Haojie Chen1 1Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Haojie Chen, Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China, Email chenhaojie97@126.comBackground: Thoracolumbar vertebral fractures are common pathological fractures caused by osteoporosis in the elderly. These fractures are challenging to detect. This study aimed to evaluate the diagnostic value of Hounsfield units for osteoporotic thoracolumbar vertebral non-compression fractures in elderly patients with low-energy fractures.Methods: The retrospective case-control study included elderly patients diagnosed with osteoporotic thoracolumbar vertebral fractures and non-fractured patients who underwent computed tomography examinations for lumbar vertebra issues during July 2017 and June 2020.Results: This study included 216 patients with fractures (38 males and 178 females; average age: 77.28± 8.68 years) and 124 patients without fractures (21 males and 103 females; average age: 75.35± 9.57 years). The difference in Hounsfield units of the target (intermediate) vertebral body significantly differed between the two groups (54.74 ± 21.84 vs 5.86 ± 5.14; p< 0.001). The ratios of Hounsfield units were also significantly different between the two groups (1.38 ± 1.60 vs 0.13 ± 0.23; p< 0.001). The cut-off value for the difference in Hounsfield units to detect osteoporotic spine fractures was 25.35, with high sensitivity (98.5%), specificity (99.9%), and the area under the curve (AUC) (0.999, 95% CI: 0.999– 1). The cut-off value for the odds ratio of Hounsfield units was 0.260, with high sensitivity (99.1%), specificity (92.7%), and AUC (0.970, 95% CI: 0.949– 0.992).Conclusion: The difference between Hounsfield units and the odds ratio of Hounsfield units might help diagnose osteoporotic thoracolumbar vertebral non-compression fractures in elderly patients with low-energy fractures.Keywords: multi-slice spiral computed tomography, thoracolumbar vertebrae, fractures, osteoporosis, morphological changes

Xiaofan Liu,1 Jianji Zeng,2 Liuxiang Li,2 Qixiu Wang,2 Junyi Chen,2 Li Ding2 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2School of Medical Business, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jianji Zeng, School of Medical Business, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email zengjianji2006@163.comPurpose: To investigate the influence mechanism of doctor-patient communication on patients’ trust, especially the mediating role of patient-physician consistency and the moderating role of perceived threat of disease.Methods: A total of 699 patients in Guangzhou, China was investigated by questionnaire. The main effect, mediating effect, and moderating effect of the model was verified by SPSS23.0 and LISREL8.71 statistical software.Results: It was revealed that doctor-patient communication has a significant positive effect on patients’ trust. The consistency between patient and physician partially mediates the relationship between doctor-patient communication and patients’ trust. Additionally, the perceived threat of the disease moderates the psychological process through which doctor-patient communication affects patients’ trust.Conclusion: Both doctor-patient communication and patient-physician consistency have predictive effects on patients’ trust. Doctor-patient communication is not only a direct influence on patient trust but also an indirect influence mediated by patient-physician consistency. Perceived threat of disease moderates the psychological process through which doctor-patient communication affects patients’ trust. Specifically, compared to a high level of perceived threat of disease, a low level of perceived threat of disease can enhance the effect of doctor-patient communication on patients’ trust. The results of this study underscore the importance of doctor-patient communication and the value of patient-physician consistency for building patients’ trust. To foster a harmonious doctor-patient relationship, medical colleges should place great emphasis on cultivating medical students’ communication skills. Hospitals should enhance on-the-job training and provide institutional support for doctors, encourage agreements between doctors and patients regarding disease diagnosis and decision-making, and be attentive to patients’ perceived threat of disease, particularly for those with high level of perceived threat of disease.Keywords: doctor-patient communication, patient-physician consistency, perceived threat of disease, patients’ trust, doctor-patient relationship

Shuping Zhang,1,&ast; Yamei Ma,1,&ast; Xiu Zang,2 Hao Heng,2 Xuekui Liu,2 Gangshan Peng,3 Ran Liu,3 Jun Liang,1,2,&ast; Houfa Geng1,2,&ast; 1Graduate School, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3The Affiliated Xuzhou Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houfa Geng; Jun Liang, Email genghoufa@xzhmu.edu.cn; liangjun@xzhmu.edu.cnAbstract: Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.Keywords: 17q12 microdeletion syndrome, HNF-1β gene, special-type diabetes, MODY5, polycystic kidneys, liver damage

Liping Feng,1,&ast; Wencong He,2,&ast; Zexuan Song,3,&ast; Bing Zhao,3 Chong Teng,3 Eryong Liu,3 Hanfang Zhu,1 Shaojun Pei,4 Lina Liu,5 Yuanyuan Song,3 Yang Zheng,3 Xiangyi Liu,2 Yanlin Zhao,3 Xichao Ou3 1Department of Microbiology, Hinggan League Center for Disease Control and Prevention, Ulanhot, 137499, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, People’s Republic of China; 3National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4School of Public Health, Peking University, Beijing, 100191, People’s Republic of China; 5Blood Transfusion Department, Hinggan League People’s Hospital, Ulanhot, 137400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xichao Ou; Yanlin Zhao, Email ouxc@chinacdc.cn; zhaoyl@chinacdc.cnBackground: Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China.Methods: This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models.Results: A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052– 4.210) and male patients (AOR = 3.858, 95% CI: 1.416– 10.511) were identified as independent risk factors associated with DR-TB.Conclusion: Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.Keywords: Mycobacterium tuberculosis, drug resistance, genetic diversity, whole-genome sequencing

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Sijia Liu,1,2,&ast; Ting Yang,1,2,&ast; Qingsong Jiang,1,2 Liang Zhang,1,2 Xinhui Shi,1,2 Xin Liu,3 Xiaoli Li1,2 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 3Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Li; Xin Liu, Email lixiaoli@cqmu.edu.cn; liux0704@tmmu.edu.cnAbstract: Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including “sepsis”, “lactate”, “lactylation”, and “epigenetic modification”. The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.Plain Language Summary: The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition. Keywords: sepsis, lactate, lactylation, epigenetic modification

Peijun Li,1,&ast; Yingqi Wang,1,&ast; Yuanyuan Cao,2 Jiacheng Shi,1 Meiling Jiang,2 Xiaoyu Han,2 Linhong Jiang,1 Yidie Bao,1 Weibing Wu,2 Xiaodan Liu1,3,4 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Liu; Weibing Wu, Email hzhp403@126.com; wwb75@126.comBackground: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.Keywords: chronic obstructive pulmonary disease, diaphragmatic atrophy, exercise training, inflammation, RhoA/ROCK signaling

Xinzhou Liu,1,2 Xiuhuan Wang,1,2 Jianke Li,1,2 Xiaofeng Shan,1,2 Zhongxiang Shi1,2 1Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University, Jinan, 250022, People’s Republic of China; 2Department of Dermatology, Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, 250022, People’s Republic of ChinaCorrespondence: Zhongxiang Shi, Hospital for Skin Diseases, Shandong First Medical University, Jinan, 250022, People’s Republic of China, Tel +86 (531)87298874, Fax +86-531-87984734, Email szxsd2003@sina.comAbstract: Darier’s disease (DD) is an autosomal dominant genodermatosis characterized by hyperkeratotic papules, often accompanied by scaling and crusting. Managing DD presents significant challenges due to the absence of an effective cure, with only symptom targeting treatments currently available. This study presents a case of refractory DD that showed poor response to established pharmacological treatments but demonstrated improvement with low-dose superficial X-ray radiotherapy (SRT). The radiation was delivered as a single 200 cGy treatment, which visibly improved the condition. Considering the different degrees of side effects, sequelae, and risk of developing radiation-induced cancer after exposure to moderate levels of radiation, it may be considered that we attempt to treat recalcitrant DD initially by applying a low dose of radiation in order to mitigate these undesired side effects. If larger doses or additional courses are necessary due to inadequate response, the risks and benefits must be carefully evaluated and discussed with patients.Keywords: Darier disease, superficial X-ray, low-dose of radiation, SRT-100

Xin Liu,1,&ast; Ruofan Xi,1,&ast; Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Jiaying Lao,1,2,&ast; Hang Tan,3,&ast; Yuyu Wu,2,&ast; Ting Ding,4 Xinqian Liu,1 Lanrong Sun,2 Xiyi Chen,2 Chongrong Zhu,2 Yiming Kang,5 Yu-Hsin Chen,2,6 Chonghui Tang,1 Fan Wang,7 Yanlong Liu2,6 1Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of neurosurgery, Hangzhou Mingzhou Brain Rehabilitation Hospital, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, People’s Republic of China; 5Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7Beijing Hui−Long−Guan Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlong Liu, School of Mental Health, Medical University, Wenzhou, 325035, People’s Republic of China, Email benjaminlyl@wmu.edu.cn Chonghui Tang, Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, People’s Republic of China, Email tangegg@163.comObjective: Cigarette smoking and low peripheral nitric oxide synthase (NOS) levels are strongly associated with sleep disorders. However, whether cerebrospinal fluid (CSF) NOS relates to sleep disorders and whether CSF NOS mediates the relationship between cigarette smoking and sleep disorders is unclear.Methods: We measured CSF levels of total NOS (tNOS) and its isoforms (inducible NOS [iNOS] and constitutive NOS [cNOS]) in 191 Chinese male subjects. We applied the Pittsburgh Sleep Quality Index (PSQI).Results: The PSQI scores of active smokers were significantly higher than those of non-smokers, while CSF tNOS, iNOS, and cNOS were significantly lower (all p < 0.001). CSF tNOS, iNOS, and cNOS were negatively associated with PSQI scores in the general population (all p < 0.001). Mediation analysis suggested that CSF tNOS, iNOS, and cNOS mediate the relationship between smoking and PSQI scores, and the indirect effect accounted for 78.93%, 66.29%, and 81.65% of the total effect, respectively.Conclusion: Cigarette smoking is associated with sleep disorders. Active smokers had significantly lower CSF levels of tNOS, iNOS, and cNOS. Furthermore, tNOS, iNOS, and cNOS mediate the relationship between cigarette smoking and sleep quality. This study provides insights into how cigarette smoke affects sleep disorders.Keywords: cerebrospinal fluid nitric oxide synthase, cigarette smoking, Pittsburgh Sleep Quality Index, sleep disorders, mediation

Tiantian Liang,1,&ast; Xianbin Liu,1,&ast; Yujun Tong,2 Qian Ding,3 Min Yang,1 Hong Ning1 1Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, People’s Republic of China; 2Department of Breast Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, Sichuan, People’s Republic of China; 3Department of Clinical Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Ning; Min Yang, Department of Pharmacy, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 12, Changjia Alley, Jingzhong Street, Mianyang, Sichuan, 621000, People’s Republic of China, Email ninghong555@126.com; ym8710@126.comAbstract: Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade’s advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.Keywords: targeting, targeted therapies, infantile hemangiomas, drug delivery systems, nanoparticle

Yujie Wang,1 Tingting Deng,1 Xi Liu,2 Xueyang Fang,1 Yongpan Mo,3 Ni Xie,4 Guohui Nie,1 Bin Zhang,1 Xiaoqin Fan1,4 1Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Department of Otolaryngology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, People’s Republic of China; 2Department of Nephrology, Shenzhen Longgang Central Hospital, Shenzhen, 518116, People’s Republic of China; 3Department of Breast Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, People’s Republic of China; 4The Bio-Bank of Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, 518035, People’s Republic of ChinaCorrespondence: Bin Zhang; Xiaoqin Fan, Email binzhang@email.szu.edu.cn; fanxiaoqin83@163.comAbstract: The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy. Keywords: tumor microenvironment, stimulus-responsive, drug delivery, cancer therapy, intelligent biomedicine

Xinyao Ding,1 Shujun Li,2 Xue Liu,2 Xiaowen Zhan,2 Zhiyuan Wang,2 Mengzhu Wang,2 Guannan Wu3 1Department of Paediatrics, Luohe Yancheng District People’s Hospital, Luohe, Henan, 462300, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, People’s Republic of China; 3Department of ICU, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, 453100, People’s Republic of ChinaCorrespondence: Shujun Li, Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, No. 88 of Jiankang road, Weihui, Henan, 453100, People’s Republic of China, Tel +8613781905766, Email ruolin2223@126.comObjective: This study explored the level of nuclear factor-ƙB (NF-ƙB) in the bronchoalveolar lavage fluid (BALF) of children with severe Mycoplasma Pneumoniae pneumonia (SMPP) and the correlation between NF-ƙB, cellular immunity, and clinical characteristics.Methods: A total of 41 hospitalized children diagnosed with SMPP were selected and included in the SMPP group, and 13 bronchial foreign bodies (FB) without infection during the same period were included in the FB group. The NF-ƙB in the BALF of participants was detected by enzyme-linked immunosorbent assay. The correlation between NF-ƙB and laboratory findings, cellular immunity, and the clinical features in children with SMPP was analyzed. The differences in chest imaging and bronchoscopy in children with SMPP were observed.Results: The levels of NF-ƙB were significantly increased in the SMPP group compared with the FB group (P < 0.001). There were correlations between different NF-ƙB pairs in the SMPP group (P < 0.01). Nuclear factor-ƙB (NF-ƙB) correlated with IL-6, the mycoplasma load in BALF, fever peak, length of hospital stay, and sputum suppository (P < 0.05). The higher the intracellular NF-ƙB level in BALF, the lower the CD3+ CD4+ value in peripheral blood (P < 0.05). Intracellular NF-ƙB and total NF-ƙB correlated with pleural effusion, pericardial effusion, and extrapulmonary complications (P < 0.05).Conclusion: NF-ƙB is involved in airway inflammation changes in children with SMPP. The higher the level of NF-ƙB in the airway, the more severe the clinical manifestations, and the longer the length of hospital stay is likely to be.Keywords: mycoplasma pneumoniae pneumonia, bronchoalveolar lavage fluid, NF-ƙB, cellular immunity, children

Cen Cheng, Jingjing Wang, Yuanyuan Cao, Erwei Gu, Xuesheng Liu Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Xuesheng Liu, Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China, Email liuxuesheng@ahmu.edu.cnIntroduction: Rectus sheath block is an emerging technique that provide effective perioperative analgesia and is related to lower perioperative opioid consumption and decrease opioid-related adverse effects. The present research is designed to explore the effect of rectus sheath block on recovery quality in patients following transabdominal midline gynecological surgery.Methods: Ninety female patients following elective transabdominal midline gynecological surgery were enrolled. Patients were randomized to group R (n = 45) which receive preoperative ultrasound-guided RSB with 0.4% ropivacaine or group C which is control group (n = 45). The primary outcome was the quality of recovery on the first postoperative day. The quality of recovery was assessed by the 40-item Quality of Recovery questionnaire (QoR-40). Secondary outcomes included the intraoperative opioid consumption, time to first flatus and time to first discharging from bed, postoperative nausea and vomiting, and patient satisfaction.Results: The patients in two groups had comparable baseline characteristics. Postoperative global QoR-40 scores were significantly better in group R than in group C (165.0[159.5-170.0] vs 155.0[150.0-157.0], respectively; median difference 12[95% confidence interval: 8-15, P< 0.001]). Preoperative RSB reduced intraoperative opioid consumption, reduced the time to first flatus, time to first discharging from bed and the post anaesthesia care unit discharge time. Furthermore, group R showed greater patient satisfaction.Conclusion: A single preoperative administration of RSB with ropivacaine improved the quality of recovery in patients following transabdominal midline gynecological surgery.Plain Language Summary: Although laparoscopic surgery accounts for a higher proportion of gynecological procedures, open gynecological surgery remains irreplaceable for some patients. Recovery from open gynecological surgery is a combination of physical injuries and psychological challenges. Consequently, accelerating functional recovery, alleviating discomfort and improving the quality of recovery in such patients is a clinical issue that we need to focus on. The QoR 40 scale is a patient-reported assessment tool which evaluates the quality of recovery in five dimensions.Ultrasound-guided rectus sheath block is a safe and effective abdominal wall nerve block for anesthesia and analgesia of umbilical and median abdominal longitudinal incisions. This study investigated the impact of rectus sheath block on the quality of postoperative recovery after open gynecological surgery using the QoR40 scale. Participants were randomized to two groups: rectus sheath block treatments and a control group receiving standard care only.Rectus sheath block improves the quality of recovery in patients undergoing open gynecological surgery one day after surgery without adverse effects, which has successfully made rapid rehabilitation from bench to bedside.Keywords: rectus sheath block, quality of recovery, transabdominal midline gynecological surgery, QoR 40

Qiwen Yu,1 Chaopeng Mei,1 Mengwei Cui,1 Qianqian He,1 Xudong Liu,2 Xiaoxiao Du2 1Department of Emergency Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Xiaoxiao Du, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi, Zhengzhou, Henan, People’s Republic of China, Email xiaoxiao5811@126.comBackground: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear.Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5).Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway.Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.Keywords: liver ischemia/reperfusion injury, nepetoidin B, MKP5, JNK/P38 pathway

Yuping Zhu,1 Xunfu Lai,1 Mengting Wang,2 Xin Tang,1 Tianyi Wan,3 Bin Li,1 Xiaoming Liu,1 Jialin Wu,1 Lei He,1 Yulin He1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Radiology, Yichang Central People’s Hospital, Yichang, People’s Republic of China; 3Department of Radiology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of ChinaCorrespondence: Yulin He, Department of Radiology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 0791 8869 3802, Email ndyfy02171@ncu.edu.cnObjective: To separate the resting-state network of patients with dental pain using independent component analysis (ICA) and analyze abnormal changes in functional connectivity within as well as between the networks.Patients and Methods: Twenty-three patients with dental pain and 30 healthy controls participated in this study. We extracted the resting-state functional network components of both using ICA. Functional connectivity differences within 14 resting-state brain networks were analyzed at the voxel level. Directional interactions between networks were analyzed using Granger causality analysis. Subsequently, functional connectivity values and causal coefficients were assessed for correlations with clinical parameters.Results: Compared to healthy controls, we found enhanced functional connectivity in the left superior temporal gyrus of anterior protrusion network and the right Rolandic operculum of auditory network in patients with dental pain (p< 0.01 and cluster-level p< 0.05, Gaussian random field corrected). In contrast, functional connectivity of the right precuneus in the precuneus network was reduced, and were significantly as well as negatively correlated to those of the Visual Analogue Scale (r=− 4.93, p=0.017), Hamilton Anxiety Scale (r=− 0.46, p=0.027), and Hamilton Depression Scale (r=− 0.563, p< 0.01), using the Spearman correlation analysis. Regarding the causal relationship between resting-state brain networks, we found increased connectivity from the language network to the precuneus in patients with dental pain (p< 0.05, false discovery rate corrected). However, the increase in causal coefficients from the verbal network to the precuneus network was independent of clinical parameters.Conclusion: Patients with toothache exhibited abnormal functional changes in cognitive-emotion-related brain networks, such as the salience, auditory, and precuneus networks, thereby offering a new imaging basis for understanding central neural mechanisms in dental pain patients.Keywords: toothache, independent component analysis, resting-state networks, Granger causality

Xulin Liu,1,&ast; Zhancheng Qiu,2,&ast; Elijah Ndhlovu,1,&ast; Yunyan Wan,3 Huapeng Sun,4 Shuai Wang,5 Yugang Cao,6 Peng Zhu1 1Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Taihe Hospital, Shiyan City, Hubei Province, People’s Republic of China; 4Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Republic of China; 5Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 6Department of Hepatobiliary and Pancreatic Surgery, Huangshi Central Hospital of Edong Healthcare Group, Huangshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Zhu, Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Tel +86 13907170712, Email zhupeng@tjh.tjmu.edu.cnPurpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection.Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis.Results: Multivariate COX regression showed that HBV DNA ≥ 10,000 IU/mL (P < 0.001), HALP score ≤ 38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III–IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001).Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.Keywords: early recurrence, hepatocellular carcinoma, HALP score, nomogram, Barcelona Clinic of Liver Cancer staging system, disease-free survival

Chunyan Guo,1,2,&ast; Xiaoxiao Liu,1,&ast; Keqing Qiu,2 Longxiang Tu,1 Dewu Liu1 1Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dewu Liu, Email ndyfy00706@ncu.edu.cnPurpose: Hypertrophic scarring (HS) is commonly described as an abnormal post-traumatic tissue repair characterized by excessive hypercellularity and extracellular matrix (ECM) deposition. Mounting evidence suggests that MALAT1 is maladjusted in many fibrotic diseases, but its contribution to HS progression remains poorly understood. Hence, we sought to elucidate the fundamental role of MALAT1 in HS.Methods: The expression of MALAT1, miR-29a-3p, and Smurf2 in skin tissues and fibroblasts was assessed by RT-qPCR and Western blotting. Furthermore, lentiviruses, RNAi, or plasmids were utilized to transfect hypertrophic scar fibroblasts (HSFs) for gene overexpression or downregulation. The biological behaviors of HSFs were quantified by the CCK-8 assay, wound healing assay, transwell assay, and flow cytometry. Mechanistically, bioinformatics analysis, dual-luciferase reporter assays, and rescue experiments were performed to verify the relationship between miR-29a-3p and MALAT1 or Smurf2.Results: Our data indicate that MALAT1, Smurf2 were overexpressed while miR-29a-3p was suppressed in HS tissues and fibroblasts. Downregulation of MALAT1 may lead to decreased proliferation, migration, and invasion of fibroblasts, accompanied by enhanced apoptosis, reduced TGF-β signal transduction, and ECM accumulation in HSFs, by enhancing miR-29a-3p and suppressing Smurf2 expression. Mechanistically, MALAT1 acted as a sponge for miR-29a-3p, while miR-29a-3p directly targeted Smurf2. More importantly, rescue experiments suggested that MALAT1 downregulation induced impact on the proliferation, migration, and invasion of HSFs could be partially overturned through miR-29a-3p knockdown or Smurf2 overexpression.Conclusion: MALAT1 knockdown inhibits the proliferation, migration, invasion, and collagen deposition of HSFs via targeting the miR-29a-3p/Smurf2 axis, which may reveal a promising therapeutic exploitable vulnerability to HS. Keywords: hypertrophic scar, fibroblasts, MALAT1, miR-29a-3p, Smurf2, TGF-β signaling pathway

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Yuling Liang,1,&ast; Yuqing Xie,1,&ast; Xiaoli Liu,1 Lihua Yu,1 Huiwen Yan,1 Zimeng Shang,1 Yuan Wu,1 Xue Cai,2 Wanxin Shi,2 Juan Du,3 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email duj656@163.com Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Traditional Chinese medicine (TCM) therapy is an important means to treat hepatocellular carcinoma (HCC), Astragalus (Latin name: Hedysarum Multijugum Maxim; Chinese name: Huangqi, HQ) and Atractylodes (Latin name: Atractylodes Macrocephala Koidz; Chinese name: Baizhu, BZ) (HQBZ), a classic herb pair, is often used in combination to HCC. However, the main components and potential mechanisms of HQBZ therapy in HCC remain unclear. This study aimed to identify the potential active ingredients and molecular mechanisms of action of HQBZ in HCC treatment.Methods: The HQBZ-Compound-Target-HCC network and HQBZ-HCC transcriptional regulatory network were constructed to screen the core active compound components and targets of HQBZ therapy for HCC. Molecular docking techniques are used to verify the stability of binding core active compound components to targets. GO and KEGG enrichment analysis were used to explore the signaling pathway of HQBZ in HCC treatment, the mechanism of HQBZ treatment of HCC was verified based on in vivo H22 tumor bearing mice and in vitro cell experiments.Results: Network pharmacology and molecular docking studies showed that HQBZ treatment of HCC was related to the targeted regulation of IL-6 and STAT3 by the active compound biatractylolide, KEGG pathway enrichment analysis suggest that HQBZ may play a role in the treatment of HCC through IL-6/STAT3 signaling pathway. In vitro experiment results proved that HQBZ could regulate IL-6/STAT3 signaling pathway transduction on CD8+T cells, inhibit CD8+T cell exhaustion and restore the function of exhausted CD8+T cells. In vivo experiment results proved that HQBZ can regulate IL-6/STAT3 signaling pathway transduction in H22 liver cancer model mouse tumor tissue, increased the proportion of tumor infiltrating CD8+T cells.Conclusion: This study found that HQBZ may play a therapeutic role in HCC by targeting IL-6 and STAT3 through biatractylolide, its mechanism of action is related to regulating IL-6/STAT3 signaling pathway, reversing T cell failure and increasing tumor infiltration CD8+T cells.Keywords: Astragalus–Atractylodes herb pair, hepatocellular carcinoma, IL-6/STAT3 signaling pathway, molecular docking, network pharmacology

Zhen Cao,1 Xiaoyu Liu,2 Xiangzhen Wang,3 Moning Guo,4 Zhongjun Guan1,5 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2School of Statistics, Capital University of Economics and Business, Beijing, People’s Republic of China; 3School of Public Health, Peking University Health Science Center, Beijing, People’s Republic of China; 4Beijing Municipal Health Big Data and Policy Research Center, Beijing, People’s Republic of China; 5Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Moning Guo, Beijing Municipal Health Big Data and Policy Research Center, No. 277, Zhao Dengyu Road, Xicheng District, Beijing, 100053, People’s Republic of China, Email guomoning@wjw.beijing.gov.cn Zhongjun Guan, Beijing Tiantan Hospital, Capital Medical University, No. 119, South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Email guanzhj@ccmu.edu.cnPurpose: As one of the pioneering pilot cities in China’s extensive Diagnosis Related Groups (DRG) -based prepayment reform, Beijing is leading a comprehensive overhaul of the prepayment system, encompassing hospitals of varying affiliations and tiers. This systematic transformation is rooted in extensive patient group data, with the commencement of actual payments on March 15, 2022. This study aims to evaluate the effectiveness of DRG payment reform by examining how it affects the cost, volume, and utilization of care for patients with neurological disorders.Patients and Methods: Utilizing the exogenous shock resulting from the implementation of the DRG-based prepayment system, we adopted the Difference-in-Differences (DID) approach to discern changes in outcome variables among DRG payment cases, in comparison to control cases, both before and following the enactment of the DRG policy. The analytical dataset was derived from patients diagnosed with neurological disorders across all hospitals in Beijing that underwent the DRG-based prepayment reform. Strict data inclusion and exclusion criteria, including reasonableness tests, were applied, defining the pre-reform timeframe as March 15th through October 31st, 2021, and the post-reform timeframe as the corresponding period in 2022. The extensive dataset encompassed 53 hospitals and encompassed hundreds of thousands of cases.Results: The implementation of DRG-based prepayment resulted in a substantial 12.6% decrease in total costs per case and a reduction of 0.96 days in length of stay. Additionally, the reform was correlated with significant reductions in overall in-hospital mortality and readmission rates. Surprisingly, the study unearthed unintended consequences, including a significant reduction in the proportion of inpatient cases classified as surgical patients and the Case Mix Index (CMI), indicating potential strategic adjustments by providers in response to the introduction of DRG payments.Conclusion: The DRG payment reform demonstrates substantial effects in restraining cost escalation and enhancing quality. Nevertheless, caution must be exercised to mitigate potential issues such as patient selection bias and upcoding.Keywords: diagnosis-related groups, payment reform, neurological disorders, DID, China

Jingzhan Huang,1,&ast; Jialong Liu,1,&ast; Jin Lan,1,&ast; Jingbo Sun,1 Kun Zhou,1 Yunyao Deng,1 Li Liang,2 Lixin Liu,1,&ast; Xiaolong Liu1 1Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Liu; Xiaolong Liu, Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, Guangdong, 510630, People’s Republic of China, Email llx0129@i.smu.edu.cn; lxl1979@i.smu.edu.cnBackground: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. Keywords: GRSF1, CRC, proliferation, metastasis, Ras/PI3K/Akt

Wanxin Shi,1,2,&ast; Huiwen Yan,1,&ast; Xiaoli Liu,1 Lihua Yu,1 Yuqing Xie,1 Yuan Wu,1 Yuling Liang,1 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People’s Republic of China, Tel/Fax +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8+T cells (CD8+Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8+Ts on PVTT prognosis.Patients and Methods: This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan–Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed.Results: We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8+Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (< 100&ast;10^9/L) and high CD8+Ts (> 320 cells/μL) had a better prognosis.Conclusion: We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8+Ts, and found that PT-8 formed by PLT and CD8+Ts was an excellent predictor of the prognosis of PVTT.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, platelet, CD8+T cells counts, prognostic model, correlation analysis

Kang Ge,1,2 Yilu Zhao,2,3 Xiao Liu,4 Ruzhi Zhang5 1Jiaxing Key Discipline of Medicine --Dermatology and Venereology, The Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 3Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 4School of Materials Science and Engineering, Changzhou University, Changzhou, Jiangsu, People’s Republic of China; 5Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Ruzhi Zhang, Department of Dermatology and STD, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, People’s Republic of China, Tel +8618761161826, Email zhangruzhi628@163.comObjective: ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical issue. With this in mind, our study explores a novel route of ALA delivery by loading acrylic nanoparticles (ANPs).Methods: ALA-ANPs were synthesized by emulsion polymerisation and characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effects of ALA-ANPs on HaCaT cell line were evaluated, including characteristics, morphological changes, protoporphyrin IX (PpIX) fluorescence kinetics, reactive oxygen species (ROS) levels, mitochondrial membrane potential and ki67 expression in these cells.Results: The ANPs had uniform sizes, smooth surfaces and excellent light transmittance, with diameters of 150– 200 nm. In contrast, the ALA - ANPs had uneven surfaces and poor light transmittance, with diameters of 220– 250 nm. During 12 hours of co-incubation of HaCaT cells with ALA, the intracellular accumulation of PpIX increased over time. Notably, after 6 hours of incubation, PpIX levels induced by 1.81 mg/mL ALA-ANPs exceeded those induced by 1.0 mM ALA (p < 0.01). CCK-8 results showed a positive correlation between PDT-induced inhibition of HaCaT cell proliferation and ALA concentration when ALA concentration remained below 2.0 mM. Compared to the 1.0 mM ALA group, the 1.81 mg/mL ALA-ANPs group showed decreased mitochondrial membrane potential, ki67 immunofluorescence intensity and cell proliferation. In contrast, ROS levels were significantly increased in the 1.81 mg/mL ALA-ANPs group (p < 0.01).Conclusion: Loading ANPs provide improved stability and potency for ALA. The ALA-ANPs-PDT approach has superior inhibitory effects on HaCaT proliferation in vitro.Keywords: 5-aminophenolvalic acid, ALA, acrylate nanoporous, photodynamic therapy

Qiaoli Wang,1,&ast; Tao Liang,2,&ast; Yuexi Li,1,&ast; Xiaoqin Liu1 1Department of Health Screening Center, Deyang Peoples’ Hospital, Deyang, Sichuan, 618000, People’s Republic of China; 2Department of Gastroenterology, Deyang Peoples’ Hospital, Deyang, Sichuan, 618000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqin Liu, Email 66823572@qq.comPurpose: The aim of this study was to evaluate the potential benefit of blood inflammation in the diagnosis of non-small cell lung cancer (NSCLC) and propose a machine-learning-based method to predict NSCLC in asymptomatic adults.Patients and Methods: A cross-sectional study was evaluated using medical records of 139 patients with non-small cell lung cancer and physical examination data from May 2022 to May 2023 of 198 healthy controls. The NSCLC cohort comprised 128 cases of adenocarcinoma, 3 cases of squamous cell carcinoma, and 8 cases of other NSCLC subtypes. The correlation between inflammatory and nutritional markers, such as monocytes, neutrophils, LMR, NLR, PLR, PHR and non-small cell lung cancer was examined. Features were selected using Python’s feature selection library and analyzed by five algorithms. The predictive ability of the model for non-small cell lung cancer diagnosis was assessed by precision, accuracy, recall, F1 score, and area under the curve (AUC).Results: The results showed that the top 14 important factors were PDW, age, TP, RBC, HGB, LYM, LYM%, RDW, PLR, LMR, PHR, MONO, MONO%, gender. Additionally, the naive Bayes (NB) algorithm demonstrated the highest overall performance in predicting adult NSCLC among the five machine learning algorithms, achieving an accuracy of 0.87, a macro average F1 score of 0.85, a weighted average F1 score of 0.87, and an AUC of 0.84.Conclusion: In feature ranking, platelet distribution width was the most important feature, and the NB algorithm performed best in predicting adult NSCLC diagnosis.Keywords: machine learning, non-small cell lung cancer, inflammatory indicators, nutritional indicators, ratio, diagnosis

Xu Liu,1,&ast; Qingfeng Liu,1,&ast; Linghong Guo,1 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423315, Fax +86-28-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comAbstract: The increasing popularity of tattoo art, including facial cosmetic tattoos, has led to a growing societal acceptance of tattoos. However, complications such as lip inflammation following cosmetic lip tattoos remain a concern. This article presents the case of a 47-year-old Asian woman who experienced recurrent lip swelling, purulent discharge, and scarring after receiving lip tattoos. Despite previous treatment with corticosteroid injections yielding unsatisfactory results, the patient showed significant improvement with topical application of 2% Crisaborole, a phosphodiesterase-4 inhibitor. Crisaborole modulates intracellular cyclic adenosine monophosphate levels, thereby reducing tissue inflammation and swelling associated with chronic cheilitis. Additionally, pulse laser therapy was effective in addressing residual tattoo pigment and scar tissue. This case highlights the therapeutic challenges of managing chronic inflammatory diseases of the lips secondary to cosmetic tattoos and introduces Crisaborole as a promising treatment option, offering insights for managing similar conditions in the future.Keywords: lip tattoo, chronic cheilitis, Crisaborole, phosphodiesterase-4 inhibitor, laser therapy

Xiaoliang Liu,1,&ast; Kecheng Lou,2,&ast; Yunmeng Zhang,3 Chuanxiao Li,1 Shenghong Wei,1 Shangzhi Feng1 1Department of Urology, Jiujiang University Clinic College/Hospital, Jiujiang, Jiangxi, People’s Republic of China; 2Department of Urology, Lanxi People’s Hospital, Jinhua, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Jiujiang College Hospital, Jiujiang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shangzhi Feng, Email 1131718266@qq.comAbstract: Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.Keywords: plant-derived extracellular vesicles, Chinese medicine preparation, nanoparticle, drug delivery nanoplatforms, nanotherapeutics

Xiang Liu,1,&ast; Zhipeng Wei,2,&ast; Long Ting,1,&ast; Xuming Liu,3 Yongqiang Shu,1 Huang Ling,1 Lifeng Li,1 Yumeng Liu,1 Guojin Xia,1 Dechang Peng,1 Haijun Li1 1Department of Radiology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, People’s Republic of China; 3Department of Radiology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dechang Peng; Haijun Li, Email pengdcdoctor@163.com; haijunli1990@163.comIntroduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA.Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging.Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores.Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.Keywords: obstructive sleep apnea, continuous positive airway pressure, diffusion tensor imaging, tract-based spatial statistics

Xingtong Chen,1,&ast; Qian Chen,1– 3,&ast; Zhigang Qin,1,&ast; Azeem Alam,3 Hailin Zhao,3 Raha West,3 Xianzhe Liu,1 Jieyu Li,1 Xin Li,1 Bin Yi,1 Daqing Ma,2,3 Jianteng Gu1 1Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Perioperative and Systems Medicine Laboratory, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 3Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK&ast;These authors contributed equally to this workCorrespondence: Jianteng Gu, Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Road, Chongqing, 400038, People’s Republic of China, Tel +86 23 68766122, Fax +86 23 65463270, Email jiantenggu@hotmail.com Daqing Ma, Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK, Email d.ma@imperial.ac.ukBackground: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury.Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery.Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China.Patients: 86 patients aged 60– 75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio.Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 μg kg− 1 for 10 min, followed by 0.5 μg kg− 1 hr− 1 for maintenance until the end of surgery.Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes.Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P< 0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups.Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs.Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.Keywords: dexmedetomidine, elderly patients, long-duration hepatobiliary and pancreatic laparotomy, perioperative renal function, perioperative pulmonary function